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Sample records for locally advanced hepatocellular

  1. Transarterial chemoembolization with drug-eluting beads versus conventional transarterial chemoembolization in locally advanced hepatocellular carcinoma

    PubMed Central

    Baur, Johannes; Ritter, Christian O; Germer, Christoph-Thomas; Klein, Ingo; Kickuth, Ralph; Steger, Ulrich

    2016-01-01

    Purpose In hepatocellular carcinoma patients with large or multinodal tumors, where curative treatment options are not feasible, transarterial therapies play a major role. Transarterial chemoembolization (TACE) with drug-eluting beads (DEB-TACE) is a promising new approach due to higher intratumoral and lower systemic concentration of the chemotherapeutic agent compared to conventional TACE (cTACE). Patients and methods In a retrospective analysis, 32 patients with hepatocellular carcinoma who received either DEB or a cTACE were compared regarding survival time, disease recurrence, and side effects such as pain and fever. Results No significant differences could be detected between the cTACE and DEB-TACE groups with regard to mean hospital stay, appearance of postinterventional fever, or 30-day mortality. However, the application of intravenous analgesics as postinterventional pain medication was needed more often in patients treated with DEB-TACE (57.1% vs 12.5%, P=0.0281). The overall median survival after the initial procedure was 10.8 months in the cTACE group and 9.2 months in the DEB-TACE group, showing no significant difference. Conclusion No survival benefit for patients treated with either DEB-TACE or cTACE was observed. Surprisingly, a higher rate of postinterventional pain could be detected after DEB-TACE. PMID:27382341

  2. Advances in managing hepatocellular carcinoma.

    PubMed

    Reataza, Marielle; Imagawa, David K

    2014-06-01

    Multiple modalities for treatment of hepatocellular carcinoma are available, depending on tumor size and number. Surgical resection remains the gold standard, so long as the residual liver function reserve is sufficient. In patients with advanced cirrhosis, liver transplantation is the preferred option, as these patients may not have adequate hepatic reserve after resection. Salvage liver transplantation has also become an option for a select few patients who recur after surgical resection. Ablative techniques have been used for palliation as well as to either completely destroy the tumor, act as an adjunct to resection, or downstage the tumor to meet Milan criteria such that a patient may be a candidate for liver transplantation. Radiofrequency ablation, microwave ablation, chemoembolization, radioembolization, and irreversible electroporation have all been used in this capacity. Currently, sorafenib is the only US Food and Drug Administration-approved chemotherapeutic for hepatocellular carcinoma. The efficacy of sorafenib, in combination with other agents, transarterial chemoembolization, and surgical resection is currently being investigated. Sunitinib and brivanib, tyrosine kinase inhibitors, have failed as potential first- or second-line options for chemotherapy. Bevacizumab in combination with erlotinib is also currently being studied. Final analysis for ramucirumab and axitinib are pending. Tivantinib, a selective mesenchymal-epithelial transition factor (MET) inhibitor, is also undergoing clinical trials for efficacy in MET-high tumors. This review serves to emphasize the current and new technologies emerging in the treatment of hepatocellular carcinoma. PMID:24810646

  3. Sorafenib Tosylate With or Without Doxorubicin Hydrochloride in Treating Patients With Locally Advanced or Metastatic Liver Cancer

    ClinicalTrials.gov

    2016-06-20

    Adult Hepatocellular Carcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma

  4. Local Ablation for Hepatocellular Carcinoma in Taiwan

    PubMed Central

    Lin, Shi-Ming

    2013-01-01

    Hepatocellular carcinoma (HCC) is the second commonest cancer in Taiwan. The national surveillance program can detect HCC in its early stages, and various curative modalities (including surgical resection, orthotopic liver transplantation, and local ablation) are employed for the treatment of small HCC. Local ablation therapies are currently advocated for early-stage HCC that is unresectable because of co-morbidities, the need to preserve liver function, or refusal of resection. Among the various local ablation therapies, the most commonly used modalities include percutaneous ethanol injection and radiofrequency ablation (RFA); percutaneous acetic acid injection and microwave ablation are used less often. RFA is more commonly employed than other local ablative modalities in Taiwan because the technique is highly effective, minimally invasive, and requires fewer sessions. RFA is therefore advocated in Taiwan as the first-line curative therapy for unresectable HCC or even for resectable HCC. However, current RFA procedures are less effective against tumors that are in high-risk or difficult-to-ablate locations, are poorly visualized on ultrasonography (US), or are large. Recent advancements in RFA in Taiwan can resolve these issues by the creation of artificial ascites or pleural effusion, application of real-time virtual US assistance, use of combination therapy before RFA, or use of switching RF controllers with multiple electrodes. This review article provides updates on the clinical outcomes and advances in local ablative modalities (mostly RFA) for HCC in Taiwan. PMID:24159599

  5. New advances in hepatocellular carcinoma

    PubMed Central

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  6. New advances in hepatocellular carcinoma.

    PubMed

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-03-28

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  7. Hepatocellular carcinoma: Advances in diagnostic imaging.

    PubMed

    Sun, Haoran; Song, Tianqiang

    2015-10-01

    Thanks to the growing knowledge on biological behaviors of hepatocellular carcinomas (HCC), as well as continuous improvement in imaging techniques and experienced interpretation of imaging features of the nodules in cirrhotic liver, the detection and characterization of HCC has improved in the past decade. A number of practice guidelines for imaging diagnosis have been developed to reduce interpretation variability and standardize management of HCC, and they are constantly updated with advances in imaging techniques and evidence based data from clinical series. In this article, we strive to review the imaging techniques and the characteristic features of hepatocellular carcinoma associated with cirrhotic liver, with emphasis on the diagnostic value of advanced magnetic resonance imaging (MRI) techniques and utilization of hepatocyte-specific MRI contrast agents. We also briefly describe the concept of liver imaging reporting and data systems and discuss the consensus and controversy of major practice guidelines. PMID:26632539

  8. Percutaneous Local Ablative Therapy for Hepatocellular Carcinoma

    PubMed Central

    Lau, W. Y.; Leung, Thomas W. T.; Yu, Simon C. H.; Ho, Stephen K. W.

    2003-01-01

    Objective To review and compare treatment result for percutaneous local ablative therapy (PLAT) with surgical resection in the treatment of small hepatocellular carcinoma (HCC). Summary Background Data PLAT is indicated for small unresectable HCC localized to the liver. From the use of ethanol to the latest technology of radiofrequency ablation, ablative techniques have been refined and their role in the management of HCC established. This review aims to give an overview of various ablative methods, including their efficacy, indications, and limitations, and also tries to look into the future of clinical trials in PLAT. Methods The authors reviewed recent papers in the English medical literature about the use of local ablative therapy for HCC. Focus was given to the results of treatment in terms of local control, progression-free survival, and overall survival, and to compare treatment results with those of surgery. Results PLAT for small HCC (<5 cm) with thermal ablation (radiofrequency ablation or microwave coagulation) can achieve effective local control of disease and is superior to ethanol injection. Progressive disease in untreated areas is a common reason for failure. Overall progression-free survival is similar to that of surgical resection. Conclusions Thermal ablation gives good local control of small HCC, is superior to ethanol, and may be comparable to surgical resection in long-term outcome. PMID:12560774

  9. Progress in systemic therapy of advanced hepatocellular carcinoma

    PubMed Central

    Gong, Xin-Lei; Qin, Shu-Kui

    2016-01-01

    Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method. In recent years, clinical studies and observations have often reported about systemic anti-cancer therapy of advanced HCC, including molecular target therapy, systemic chemotherapy and immunotherapy. In this article, we review these treatment modalities to provide a reference for clinicians. PMID:27547002

  10. Advances of imaging for hepatocellular carcinoma.

    PubMed

    Choi, Byung Ihn

    2010-07-01

    A variety of imaging modalities, including ultrasound (US), computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography, are currently used in evaluating patients with chronic liver disease and suspected hepatocellular carcinoma (HCC). Further technological advancement will undoubtedly have a major impact on liver tumor imaging. Increased speed of data acquisition and consequently shorter scan times in CT and MRI show further improvement in resolution by further reducing motion artifacts. Development of new contrast materials for liver tumor imaging in US and MRI improve tumor detection and characterization by increasing the contrast resolution. Currently available advanced US techniques in the evaluation of HCC are various harmonic imaging techniques with contrast agents, volume imaging, and recently, US elastography, that has been developing and might play a role in characterizing liver nodules in the future. The latest advance in CT is the multidetector (MD) CT scanner where a 256- or 320-detector CT was introduced. Recent studies describe the high sensitivity of double arterial phase imaging in hepatic tumor detection and the usefulness of CT angiography by using MD CT in a detailed assessment of hepatic arterial anatomy using a three-dimensional dataset. In addition, perfusion CT imaging is also being developed and can be used for the characterization and treatment monitoring of HCC. Dual-energy CT with new technology is also continuously progressing. Advances in MR technology, including hardware and pulse sequence implementation, allow acquisition times to be reduced to the time frame of one breathhold, providing multiphasic dynamic MRI. Functional MRI including diffusion-weighted MRI, MR elastography, and new MR contrast agent with dual function have been investigated for the clinical utility of detection and characterization of HCCs. Functional MRI has a potential to be a promising technique for assessing HCC. PMID:20616584

  11. Local-regional treatment of hepatocellular carcinoma.

    PubMed

    Lencioni, Riccardo; Crocetti, Laura

    2012-01-01

    Local-regional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided tumor ablation is recommended in patients with early-stage HCC when surgical options are precluded and can replace resection in selected patients. Radiofrequency (RF) ablation has shown superior anticancer effects and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials and is currently established as the standard method for local tumor treatment. Novel thermal and nonthermal techniques for tumor ablation, including microwave ablation and irreversible electroporation, seem to have potential to overcome the limitations of RF ablation and warrant further clinical investigation. Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with asymptomatic noninvasive multinodular tumors in intermediate-stage disease. Embolic microspheres that have the ability to release a drug in a controlled and sustained fashion have been shown to substantially increase the safety and efficacy of TACE in comparison to conventional ethiodized oil-based regimens. The available data for radioembolization with yttrium 90 suggest that this is a potential new option for patients with HCC, and future studies should be devoted to assessments of the role of radioembolization in the treatment algorithm for HCC. PMID:22190656

  12. Impact of Metronomic UFT/Cyclophosphamide Chemotherapy and Antiangiogenic Drug Assessed in a New Preclinical Model of Locally Advanced Orthotopic Hepatocellular Carcinoma1

    PubMed Central

    Tang, Terence C; Man, Shan; Lee, Christina R; Xu, Ping; Kerbel, Robert S

    2010-01-01

    Hepatocellular carcinoma (HCC) is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce the extensive liver disease associated with HCC or metastasize. To address this deficiency, we developed an orthotopic model. Human HCC cells were transfected with the gene encoding secretable β-subunit human choriogonadotropin (β-hCG), which was used as a surrogate marker of tumor burden. The HCC cells were implanted into the left liver lobe of severe combined immunodeficient (SCID) mice, after which the efficacy of different therapies was evaluated on established, but liver-confined human Hep3B cell line HCC. Treatments included sorafenib or metronomic chemotherapy using cyclophosphamide (CTX), UFT, an oral 5-fluorouracil prodrug, or doxorubicin either alone or in various combinations, with or without an antiangiogenic agent, DC101, an anti-vascular endothelial growth factor receptor-2 antibody. Sorafenib inhibited tumor growth in a dose-dependent manner but caused severe weight loss in SCID mice, thus necessitating use of DC101 in subsequent experiments. Although less toxicity was observed using either single or doublet metronomic chemotherapy without any added antiangiogenic agent, none, provided survival benefit. In contrast, significantly improved overall survival was observed using various combinations of metronomic chemotherapy regimens such as UFT + CTX with DC101. In conclusion, using this model of liver-confined but advanced HCC suggests that the efficacy of a targeted antiangiogenic drug or metronomic chemotherapy can be mutually enhanced by concurrent combination treatment. PMID:20234820

  13. Technical advances in external radiotherapy for hepatocellular carcinoma

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  14. Technical advances in external radiotherapy for hepatocellular carcinoma.

    PubMed

    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-08-28

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  15. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

    PubMed Central

    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  16. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    PubMed

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  17. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances

    PubMed Central

    Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288

  18. Recent advances in multidisciplinary management of hepatocellular carcinoma

    PubMed Central

    Gomaa, Asmaa I; Waked, Imam

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

  19. Recent advances in the imaging of hepatocellular carcinoma

    PubMed Central

    You, Myung-Won; Kim, Kyoung Won; Lee, So Jung; Shin, Yong Moon; Kim, Jin Hee; Lee, Moon-Gyu

    2015-01-01

    The role of imaging is crucial for the surveillance, diagnosis, staging and treatment monitoring of hepatocellular carcinoma (HCC). Over the past few years, considerable technical advances were made in imaging of HCCs. New imaging technology, however, has introduced new challenges in our clinical practice. In this article, the current status of clinical imaging techniques for HCC is addressed. The diagnostic performance of imaging techniques in the context of recent clinical guidelines is also presented. PMID:25834808

  20. Recent Advances in Radiofrequency Ablation for the Management of Hepatocellular Carcinoma

    PubMed Central

    Himoto, Takashi; Kurokohchi, Kazutaka; Watanabe, Seishiro; Masaki, Tsutomu

    2012-01-01

    Contexts Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. Because less than 20% of patients with HCC are resectable, various types of non-surgical treatment have been developed. Evidence Acquisition At present, radiofrequency ablation (RFA) is accepted as the standard local treatment for patients with HCC because of its superior local control and overall survival compared to other local treatments. Results New devices for RFA and combination treatments of RFA with other procedures have been developed to improve anti-tumoral effects. Conclusions This review mainly focuses on the status of RFA in the management of HCC and recent advances in RFA treatment technology. PMID:23162600

  1. Management of Hepatocellular Adenoma: Recent Advances.

    PubMed

    Agrawal, Shefali; Agarwal, Sheela; Arnason, Thomas; Saini, Sanjay; Belghiti, Jacques

    2015-07-01

    Hepatocellular adenoma (HCA) is a rare benign liver cell neoplasm that occurs more frequently in young women with a history of prolonged use of oral contraceptives. Surgical resection is considered because of the risk of hemorrhage in 25% and of malignant transformation in 5% of patients with HCA. HCA is a heterogeneous disease comprising 3 subtypes with distinct molecular and complication profiles. The inflammatory or telangiectatic subtype is at increased risk for hemorrhage, the β-catenin-activated subtype is at increased risk for malignant transformation, and the hepatocyte nuclear factor-1α-inactivated or steatotic subtype is at the least risk for complications. One-third of the patients with HCA have multiple tumors on imaging with no increased risk of complications. Magnetic resonance imaging is the modality of choice for the diagnosis and subtype characterization of HCA. Systematic resection of HCA is recommended in male patients owing to the higher incidence of malignant transformation, and surgical excision in women should be reserved for tumors 5 cm or larger associated with an increased risk of complications. Cessation of hormonal therapy and radiologic surveillance in women with HCA tumors smaller than 5 cm shows that the vast majority of HCA remain stable or undergo spontaneous regression. Percutaneous core needle biopsy is of limited value because the therapeutic strategy is based primarily on patient sex and tumor size. Transarterial embolization is the initial treatment for HCA complicated by hemorrhage. Pregnancy should not be discouraged in the presence of HCA, however, frequent sonographic surveillance is recommended. PMID:24909909

  2. Chemotherapy for advanced hepatocellular carcinoma in the sorafenib age

    PubMed Central

    Miyahara, Koji; Nouso, Kazuhiro; Yamamoto, Kazuhide

    2014-01-01

    The kinase inhibitor sorafenib is the only systemic therapy proven to have a positive effect on survival of patients with advanced hepatocellular carcinoma (HCC). After development of sorafenib and its introduction as a therapeutic agent used in the clinic, several critical questions have been raised. Clinical parameters and biomarkers predicting sorafenib efficacy are the most important issues that need to be elucidated. Although it is difficult to know the responders in advance using conventional characteristics of patients, there are specific serum cytokines and/or gene amplification in tumor tissues that have been reported to predict efficacy of sorafenib. Risk and benefits of continuation of sorafenib beyond radiological progression is another issue to consider because no other standard therapy for advanced HCC as yet exists. In addition, effectiveness of the expanded application of sorafenib is still controversial, although a few studies have shed some light on combinational treatment with sorafenib for intermediate-stage HCC. Recently, over 50 relevant drugs have been developed and are currently under investigation. The efficacy of some of these drugs has been extensively examined, but none have demonstrated any superiority over sorafenib, so far. However, there are several drugs that have shown efficacy for treatment after sorafenib failure, and these are proceeding to further studies. To address these issues and questions, we have done extensive literature review and summarize the most current status of therapeutic application of sorafenib. PMID:24764653

  3. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome

    PubMed Central

    Bodzin, Adam S; Busuttil, Ronald W

    2015-01-01

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients. PMID:26019732

  4. Yttrium-90 radioembolization for advanced inoperable hepatocellular carcinoma

    PubMed Central

    Lee, Victor Ho-Fun; Leung, Dennis KC; Luk, Mai-Yee; Tong, Chi-Chung; Law, Martin WM; Ng, Sherry CY; Wong, Ka-Kin; Poon, Ronnie TP; Kwong, Dora LW; Leung, To-Wai

    2015-01-01

    Background Advanced inoperable hepatocellular carcinoma (HCC) conferring a grave prognosis may benefit from yttrium-90 (90Y) radioembolization. Methods Thirty patients with advanced inoperable HCC including those with any lesion >8 cm in maximal diameter or multiple bi-lobar lesions (totally more than five lesions), or portal vein thrombosis treated with radioembolization were reviewed. Treatment efficacy and safety were evaluated. Univariate and multivariate analyses were performed for identifying potential prognostic factors. Results After a median follow-up of 18.3 months, the response rate was 30.0%, and the disease control rate was 50.0%. Median overall progression-free survival (PFS) and overall survival (OS) were 3.3 months and 13.2 months, respectively. Longer median PFS was noted in those who had transarterial chemoembolization before radioembolization (7.3 months vs 3.1 months; P=0.021) and duration of alfafeto protein (AFP) response ≥6 months (11.8 months vs 3.0 months; P<0.001). Longer median OS was also revealed in those without portal vein thrombosis (17.1 months vs 4.4 months; P=0.015) and those whose duration of AFP response was ≥6 months (21.2 months vs 8.6 months; P=0.001). Seventeen patients (56.7%) developed treatment-related complications including five (16.7%) grade 3 events. Multivariate analysis revealed that treatment responders (P=0.001) and duration of AFP response ≥6 months (P=0.006) were prognostic of PFS, whereas the absence of portal vein invasion (P=0.025), treatment responders (P=0.010), and duration of AFP response ≥6 months (P=0.001) were prognostic of OS. Conclusion 90Y radioembolization is an alternative treatment with a promising outcome for poor-risk advanced inoperable HCC. PMID:26640386

  5. Lapatinib in Treating Patients With Locally Advanced or Metastatic Biliary Tract or Liver Cancer That Cannot Be Removed By Surgery

    ClinicalTrials.gov

    2014-12-18

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Localized Unresectable Adult Primary Liver Cancer; Recurrent Adult Primary Liver Cancer; Recurrent Extrahepatic Bile Duct Cancer; Recurrent Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Cancer; Unresectable Gallbladder Cancer

  6. Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma

    PubMed Central

    Ma, Ming-Chun; Chen, Yen-Yang; Li, Shau-Hsuan; Cheng, Yu-Fan; Wang, Chih-Chi; Chiu, Tai-Jan; Pei, Sung-Nan; Liu, Chien-Ting; Huang, Tai-Lin; Huang, Chen-Hua; Chen, Yen-Hao; Rau, Kun-Ming

    2014-01-01

    Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were refractory to sorafenib received doxorubicin (50 mg/m2) and cisplatin (50 mg/m2) infusions into the liver via the transhepatic artery. Between January 2005 and December 2011, a total of 50 patients with advanced HCC received this treatment regimen. The overall response rate (ORR) was 22% in all treated patients. In patients who received at least 2 cycles of IACT, the ORR was 36.7%, and the disease control rate was 70%. Survival rate differed significantly between patients who received only one cycle of IACT (group I) and those who received several cycles (group II). The median progression-free survival was 1.3 months and 5.8 months in groups I and II, respectively (P < 0.0001). The median overall survival was 8.3 months for all patients and was 3.1 months and 12.0 months in groups I and II, respectively (P < 0.0001). The most common toxicity was alopecia. Four patients developed grade 3 or 4 leukopenia. Worsening of liver function, nausea, and vomiting were uncommon side effects. This study demonstrated clinical efficacy and tolerable side effects of repeated IACT with doxorubicin and cisplatin in advanced HCC. Our regimen can be an alternative choice for patients with adequate liver function who do not want to receive continuous infusion of IACT. PMID:24967421

  7. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  8. Recent advances in the surgical treatment of hepatocellular carcinoma.

    PubMed

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-10-21

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  9. Recent advances in the surgical treatment of hepatocellular carcinoma

    PubMed Central

    Morise, Zenichi; Kawabe, Norihiko; Tomishige, Hirokazu; Nagata, Hidetoshi; Kawase, Jin; Arakawa, Satoshi; Yoshida, Rie; Isetani, Masashi

    2014-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. The treatment of HCC is complex and complicated by the severity of associated chronic liver disease, the stage of HCC, and the clinical condition of the patient. Liver resection (LR) is one of the most efficient treatments for patients with HCC, with an expected 5-year survival of 38%-61% depending on the stage of the disease. Improved liver function assessment, increased understanding of segmental liver anatomy from advanced imaging studies, and surgical technical progress are important factors that have led to reduced mortality in patients with HCC. The indication for LR may be expanded due to emerging evidences from laparoscopic hepatectomies and combined treatments with newly developed chemotherapies. Liver transplantation (LT) is considered as an ideal treatment for removal of existing tumors and the injured/preneoplastic underlying liver tissue with impaired liver function and the risk of multicentric carcinogenesis that results from chronically injured liver. However, LT is restricted to patients with minimal risk of tumor recurrence under immunosuppression. The expansion of criteria for LT in HCC patients is still under trial and discussion. Limited availability of grafts, as well as the risk and the cost of transplantation have led to considerable interest in expansion of the donor pool, living donor-related transplantation, and combined treatment involving LR and LT. This highlight presents evidence concerning recent studies evaluating LR and LT in HCC patients. In addition, alternative therapies for the treatment of early stage tumors and the management of patients on transplant waiting lists are discussed. PMID:25339825

  10. Complete remission of advanced hepatocellular carcinoma by radiofrequency ablation after sorafenib therapy

    PubMed Central

    Park, Jung Gil; Park, Soo Young; Lee, Hye Won

    2015-01-01

    Sorafenib, a potent multikinase inhibitor, lead to a significant improvement in progression free survival and overall survival in patients with advanced hepatocellular carcinoma (HCC). Though sorafenib has proven its efficacy in advanced stage HCC, there are limited reports on the role of sorafenib allowing for curative treatment by down-staging. We herein report a case of advanced HCC with vascular invasion, which showed treatment response by sorafenib therapy as to allow for radiofrequency ablation as curative treatment. The patient was followed-up for 6 mo without recurrence with continued sorafenib therapy. PMID:25741170

  11. Molecularly targeted therapy for advanced hepatocellular carcinoma - a drug development crisis?

    PubMed Central

    Thillai, Kiruthikah; Ross, Paul; Sarker, Debashis

    2016-01-01

    Hepatocellular carcinoma is the fastest growing cause of cancer related death globally. Sorafenib, a multi-targeted kinase inhibitor, is the only drug proven to improve outcomes in patients with advanced disease offering modest survival benefit. Although comprehensive genomic mapping has improved understanding of the genetic aberrations in hepatocellular cancer (HCC), this knowledge has not yet impacted clinical care. The last few years have seen the failure of several first and second line phase III clinical trials of novel molecularly targeted therapies, warranting a change in the way new therapies are investigated in HCC. Potential reasons for these failures include clinical and molecular heterogeneity, trial design and a lack of biomarkers. This review discusses the current crisis in HCC drug development and how we should learn from recent trial failures to develop a more effective personalised treatment paradigm for patients with HCC. PMID:26909132

  12. Efficacy and Tolerability of ABT-869 Versus Sorafenib in Advanced Hepatocellular Carcinoma (HCC)

    ClinicalTrials.gov

    2012-09-07

    Hepatocellular Carcinoma Non-resectable; Hepatocellular Carcinoma Recurrent; Carcinoma, Hepatocellular; Liver Diseases; Neoplasms by Histologic Type; Digestive System Neoplasms; Carcinoma; Liver Neoplasms; Neoplasms; Neoplasms by Site; Digestive System Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial

  13. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    PubMed

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD. PMID:25786448

  14. Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

    PubMed Central

    Bouattour, Mohamed; Payancé, Audrey; Wassermann, Johanna

    2015-01-01

    Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimizing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used. PMID:26380650

  15. Investigating the Pretreatment miRNA Expression Patterns of Advanced Hepatocellular Carcinoma Patients in Association with Response to TACE Treatment

    PubMed Central

    El-Halawany, Medhat S.; Ismail, Heba M.; Zeeneldin, Ahmed A.; Elfiky, Ammar; Tantawy, Marwa; Kobaisi, Mohamed H.; Hamed, Ikram; Abdel Wahab, Abdel Hady A.

    2015-01-01

    Hepatocellular carcinoma (HCC) is a lethal malignancy with poor prognosis and limited treatment options. Transarterial chemoembolization (TACE) using chemotherapy agents—doxorubicin and cisplatin—is an accepted treatment option for locally advanced hepatocellular carcinoma. In the current study, we analyzed the expression pattern of a selected panel of 94 miRNAs in archival samples that were collected prior to treatment from 15 Egyptian patients diagnosed with advanced hepatocelleular carcinoma. We observed an overall increase in miRNA expression in HCC samples compared with normal subjects. Out of 94 examined miRNAs, 53 were significantly upregulated while 3 miRNAs were downregulated in HCC samples compared to normal liver samples. Comparing the pretreatment miRNA expression profiles in HCC patients and the patients response to TACE treatment resulted in the identification of a set of 12 miRNAs that are significantly upregulated in nonresponders group. This miRNA panel includes miR-10a-1, miR-23a-1, miR-24, miR-26a, miR-27a, miR-30c, miR-30e, miR-106b, miR-133b, miR-199a, miR-199-3p, and miR-200b. Furthermore, we observed that a panel of 10 miRNAs was significantly associated with patients' survival status at 1 year. These results highlight the potential implications of pretreatment miRNAs expression profiling in prediction of the patients' response to TACE treatment in liver cancer. PMID:25811030

  16. Recent Advances in CT and MR Imaging for Evaluation of Hepatocellular Carcinoma

    PubMed Central

    Lee, Jeong Min; Yoon, Jeong-Hee; Joo, Ijin; Woo, Hyun Sik

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Accurate diagnosis and assessment of disease extent are crucial for proper management of patients with HCC. Imaging plays a crucial role in early detection, accurate staging, and the planning of management strategies. A variety of imaging modalities are currently used in evaluating patients with suspected HCC; these include ultrasound, computed tomography (CT), magnetic resonance imaging (MRI), nuclear medicine, and angiography. Among these modalities, dynamic MRI and CT are regarded as the best imaging techniques available for the noninvasive diagnosis of HCC. Recent improvements in CT and MRI technology have made noninvasive and reliable diagnostic assessment of hepatocellular nodules possible in the cirrhotic liver, and biopsy is frequently not required prior to treatment. Until now, the major challenge for radiologists in imaging cirrhosis has been the characterization of small cirrhotic nodules smaller than 2 cm in diameter. Further technological advancement will undoubtedly have a major impact on liver tumor imaging. The increased speed of data acquisition in CT and MRI has allowed improvements in both spatial and temporal resolution, which have made possible a more precise evaluation of the hemodynamics of liver nodules. Furthermore, the development of new, tissue-specific contrast agents such as gadoxetic acid has improved HCC detection on MRI. In this review, we discuss the role of CT and MRI in the diagnosis and staging of HCC, recent technological advances, and the strengths and limitations of these imaging modalities. PMID:24159569

  17. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

    PubMed

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil; Han, Kwang Hyub; Kim, Soon Il

    2016-09-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  18. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy

    PubMed Central

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil

    2016-01-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate <10%. Localized concurrent chemoradiotherapy (CCRT), followed by hepatic arterial infusion chemotherapy (HAIC), was recently introduced in this setting. Here, we report our early experience with living donor liver transplantation (LDLT) in such patients after successful down-staging of HCC through CCRT and HAIC. Between December 2011 and September 2012, eight patients with locally advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3–12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10–22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  19. Advanced local area network concepts

    NASA Technical Reports Server (NTRS)

    Grant, Terry

    1985-01-01

    Development of a good model of the data traffic requirements for Local Area Networks (LANs) onboard the Space Station is the driving problem in this work. A parameterized workload model is under development. An analysis contract has been started specifically to capture the distributed processing requirements for the Space Station and then to develop a top level model to simulate how various processing scenarios can handle the workload and what data communication patterns result. A summary of the Local Area Network Extendsible Simulator 2 Requirements Specification and excerpts from a grant report on the topological design of fiber optic local area networks with application to Expressnet are given.

  20. Predictive Factor of Local Recurrence after Balloon-Occluded TACE with Miriplatin (MPT) in Hepatocellular Carcinoma

    PubMed Central

    Ishikawa, Toru; Abe, Satoshi; Inoue, Ryousuke; Sugano, Tomoyuki; Watanabe, Yuhsuke; Iwanaga, Akito; Seki, Keiichi; Honma, Terasu; Nemoto, Takeo; Takeda, Keiko; Yoshida, Toshiaki

    2014-01-01

    Background Miriplatin (MPT) is a novel platinum complex used in TACE that shows promise for the treatment of hepatocellular carcinoma (HCC). However, rapid washout has been reported in some cases. Therefore, various methods of administration with MPT have been attempted to increase its therapeutic efficacy. One hopeful method is balloon-occluded TACE (B-TACE), but the therapeutic efficacy of B-TACE with MPT has not been evaluated. Aim To investigate the treatment outcomes and factors involved in local recurrence after B-TACE with MPT in HCC. Methods This study included 51 patients (55 nodules) with HCC lesions equal or less than 5 cm in diameter who underwent B-TACE with MPT between January 2012 and June 2013. Local recurrence after B-TACE with MPT and factors associated with local recurrence were evaluated. Results The overall local recurrence rate was 11.1% at 6 months and 26.2% at 12 months. The local recurrence rate did differ significantly depending on CT values immediately after B-TACE with MPT. Multivariate analysis also showed that the CT value after B-TACE with MPT was the only factor related to local recurrence after B-TACE. Conclusions B-TACE with MPT achieves relatively good local control of HCC. The plain CT value immediately after B-TACE with MPT is a predictive factor for local recurrence. In patients with unsatisfactory CT values, locoregional therapy or additional treatment is required. PMID:25047920

  1. The effect of locoregional therapies in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Sarpel, Umut; Spivack, John H.; Berger, Yaniv; Heskel, Marina; Aycart, Samantha N.; Sweeney, Robert; Edwards, Martin P.; Labow, Daniel M.; Kim, Edward

    2016-01-01

    Background & aims It is unknown whether the addition of locoregional therapies (LRTx) to sorafenib improves prognosis over sorafenib alone in patients with advanced hepatocellular carcinoma (HCC). The aim of this study was to assess the effect of LRTx in this population. Methods A retrospective analysis was performed of patients with advanced HCC as defined by extrahepatic metastasis, lymphadenopathy >2 cm, or gross vascular invasion. Sorafenib therapy was required for inclusion. Survival of patients who received LRTx after progression to advanced stage was compared to those who did not receive LRTx. Results Using an intention to treat analysis of 312 eligible patients, a propensity weighted proportional hazards model demonstrated LRTx as a predictor of survival (HR = 0.505, 95% CI: 0.407–0.628; P < 0.001). The greatest benefit was seen in patients with the largest tumor burden (HR = 0.305, 95% CI: 0.236–0.393; P < 0.01). Median survival in the sorafenib arm was 143 days (95% CI: 118–161) vs. 247 days (95% CI: 220–289) in the sorafenib plus LRTx arm (P < 0.001). Conclusions These results demonstrate a survival benefit with the addition of LRTx to sorafenib for patients with advanced HCC. These findings should prompt a prospective clinical trial to further assess the role of LRTx in patients with advanced HCC. PMID:27154804

  2. Induction therapy for locally advanced thymoma.

    PubMed

    Riely, Gregory J; Huang, James

    2010-10-01

    Thymomas are the most frequently encountered tumors of the mediastinum and often present with either localized or locally advanced disease. The prognosis in thymoma has been consistently shown to correspond to the invasiveness of the tumor (as represented by the Masaoka stage of the tumor) and the completeness of surgical resection. Because treatment with a variety of different chemotherapy regimens has demonstrated radiographic response rates greater than 50% in patients with advanced thymoma, a number of investigators have explored the use of preoperative (induction, neoadjuvant) therapy for patients with locally advanced thymoma. In this review, we summarize the published experience with preoperative therapy for thymoma and discuss ongoing clinical trials exploring multimodality therapy for treatment of locally advanced thymoma. PMID:20859127

  3. Chemotherapy advances in locally advanced head and neck cancer.

    PubMed

    Georges, Peter; Rajagopalan, Kumar; Leon, Chady; Singh, Priya; Ahmad, Nadir; Nader, Kamyar; Kubicek, Gregory J

    2014-12-10

    The management of locally advanced unresectable head and neck squamous cell cancer (HNSCC) continues to improve. One of the major advances in the treatment of HNSCC was the addition of chemotherapy to radiation in the treatment of non-surgical patients. The majority of the data regarding chemotherapy in HNSCC involve cisplatin chemotherapy with concurrent radiation. However, several new approaches have included targeted therapy against epidermal growth factor receptor and several recent studies have explored the role of induction chemotherapy in the treatment of HNSCC. The purpose of this article is to provide an overview of the role of chemotherapy in the treatment of locally advanced HNSCC. PMID:25493232

  4. Optimized management of advanced hepatocellular carcinoma: Four long-lasting responses to sorafenib

    PubMed Central

    Abbadessa, Giovanni; Rimassa, Lorenza; Pressiani, Tiziana; Carrillo-Infante, Cynthia; Cucchi, Emanuele; Santoro, Armando

    2011-01-01

    The therapeutic options for hepatocellular carcinoma (HCC) have been so far rather inadequate. Sorafenib has shown an overall survival benefit and has become the new standard of care for advanced HCC. Nevertheless, in clinical practice, some patients are discontinuing this drug because of side effects, and misinterpretation of radiographic response may contribute to this. We highlight the importance of prolonged sorafenib administration, even at reduced dose, and of qualitative and careful radiographic evaluation. We observed two partial and two complete responses, one histologically confirmed, with progression-free survival ranging from 12 to 62 mo. Three of the responses were achieved following substantial dose reductions, and a gradual change in lesion density preceded or paralleled tumor shrinkage, as seen by computed tomography. This report supports the feasibility of dose adjustments to allow prolonged administration of sorafenib, and highlights the need for new imaging criteria for a more appropriate characterization of response in HCC. PMID:21633647

  5. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (p<0.05). Multivariate analyses revealed that treatment response, etiology, Child-Pugh grading, and level of protein induced by the vitamin K antagonist- II (PIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  6. Chemotherapy and target therapy for hepatocellular carcinoma: New advances and challenges

    PubMed Central

    Deng, Gan-Lu; Zeng, Shan; Shen, Hong

    2015-01-01

    Primary liver cancer is one of the commonest causes of death. Hepatocellular carcinoma (HCC) accounts for 90% of primary liver cancers. For patients with unresectable or metastatic HCC, conventional chemotherapy is of limited or no benefit. Sorafenib is the only systemic treatment to demonstrate a statistically significant but modest overall survival benefit, leading to an era of targeted agents. Many clinical trials of targeted drugs have been carried out with many more in progress. Some drugs like PTK787 showed potential benefits in the treatment of HCC. Despite these promising breakthroughs, patients with HCC still have a dismal prognosis. Recently, both a phase III trial of everolimus and a phase II clinical trial of trebananib failed to demonstrate effective antitumor activity in advanced HCC. Sorafenib still plays a pivotal role in advanced HCC, leading to further explorations to exert its maximum efficacy. Combinations targeted with chemotherapy or transarterial chemoembolization is now being tested and might bring about advances. New targeted agents such as mammalian target of rapamycin inhibitors are under investigation, as well as further exploration of the mechanism of hepatocarcinogenesis. PMID:25914779

  7. YAP Subcellular Localization and Hippo Pathway Transcriptome Analysis in Pediatric Hepatocellular Carcinoma

    PubMed Central

    LaQuaglia, Michael J.; Grijalva, James L.; Mueller, Kaly A.; Perez-Atayde, Antonio R.; Kim, Heung Bae; Sadri-Vakili, Ghazaleh; Vakili, Khashayar

    2016-01-01

    Pediatric hepatocellular carcinoma (HCC) is a rare tumor which is associated with an extremely high mortality rate due to lack of effective chemotherapy. Recently, the Hippo pathway and its transcriptional co-activator Yes-associated protein (YAP) have been shown to play a role in hepatocyte proliferation and development of HCC in animal models. Therefore, we sought to examine the activity of YAP and the expression of Hippo pathway components in tumor and non-neoplastic liver tissue from 7 pediatric patients with moderately differentiated HCC. None of the patients had underlying cirrhosis or viral hepatitis, which is commonly seen in adults with HCC. This highlights a major difference in the pathogenesis of HCC between children and adults. We found a statistically significant increase in YAP nuclear localization in 100% of tumors. YAP target gene (CCNE1, CTGF, Cyr61) mRNA expression was also increased in the tumors that had the most significant increase in YAP nuclear localization. Based on Ki67 co-localization studies YAP nuclear localization was not simply a marker of proliferation. Our results demonstrate a clear increase in YAP activity in moderately differentiated pediatric HCC, providing evidence that it may play an important role in tumor survival and propagation. PMID:27605415

  8. YAP Subcellular Localization and Hippo Pathway Transcriptome Analysis in Pediatric Hepatocellular Carcinoma.

    PubMed

    LaQuaglia, Michael J; Grijalva, James L; Mueller, Kaly A; Perez-Atayde, Antonio R; Kim, Heung Bae; Sadri-Vakili, Ghazaleh; Vakili, Khashayar

    2016-01-01

    Pediatric hepatocellular carcinoma (HCC) is a rare tumor which is associated with an extremely high mortality rate due to lack of effective chemotherapy. Recently, the Hippo pathway and its transcriptional co-activator Yes-associated protein (YAP) have been shown to play a role in hepatocyte proliferation and development of HCC in animal models. Therefore, we sought to examine the activity of YAP and the expression of Hippo pathway components in tumor and non-neoplastic liver tissue from 7 pediatric patients with moderately differentiated HCC. None of the patients had underlying cirrhosis or viral hepatitis, which is commonly seen in adults with HCC. This highlights a major difference in the pathogenesis of HCC between children and adults. We found a statistically significant increase in YAP nuclear localization in 100% of tumors. YAP target gene (CCNE1, CTGF, Cyr61) mRNA expression was also increased in the tumors that had the most significant increase in YAP nuclear localization. Based on Ki67 co-localization studies YAP nuclear localization was not simply a marker of proliferation. Our results demonstrate a clear increase in YAP activity in moderately differentiated pediatric HCC, providing evidence that it may play an important role in tumor survival and propagation. PMID:27605415

  9. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

    PubMed Central

    Colombo, Giorgio Lorenzo; Cammà, Calogero; Attili, Adolfo Francesco; Ganga, Roberto; Gaeta, Giovanni Battista; Brancaccio, Giuseppina; Franzini, Jean Marie; Volpe, Marco; Turchetti, Giuseppe

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden. Purpose The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated. Results Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed. Conclusion The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. PMID:26527877

  10. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial

    PubMed Central

    Kawata, S; Yamasaki, E; Nagase, T; Inui, Y; Ito, N; Matsuda, Y; Inada, M; Tamura, S; Noda, S; Imai, Y; Matsuzawa, Y

    2001-01-01

    Chemotherapy is not effective for hepatocellular carcinoma (HCC). HMG-CoA redutase inhibitors have cytostatic activity for cancer cells, but their clinical usefulness is unknown. To investigate whether pravastatin, a potent HMG-CoA reductase inhibitor, prolongs survival in patients with advanced HCC, this randomized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital. 91 consecutive patients <71 years old (mean age 62) with unresectable HCC were enroled in this study. 8 patients were withdrawn because of progressive liver dysfunction; 83 patients were randomized to standard treatment with or without pravastatin. All patients underwent transcatheter arterial embolization (TAE) followed by oral 5-FU 200 mg−1d for 2 months. Patients were then randomly assigned to control (n = 42) and pravastatin (n = 41) groups. Pravastatin was administered at a daily dose of 40 mg. The effect of pravastatin on tumour growth was assessed by ultrasonography. Primary endpoint was death due to progression of HCC. The duration of pravastatin administration was 16.5 ± 9.8 months (mean ± SD). No patients in either group were lost to follow-up. Median survival was 18 months in the pravastatin group versus 9 months in controls (P = 0.006). The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival. Pravastatin prolonged the survival of patients with advanced HCC, suggesting its value for adjuvant treatment. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11286466

  11. Predictive biomarkers of sorafenib efficacy in advanced hepatocellular carcinoma: Are we getting there?

    PubMed Central

    Shao, Yu-Yun; Hsu, Chih-Hung; Cheng, Ann-Lii

    2015-01-01

    Sorafenib is the current standard treatment for advanced hepatocellular carcinoma (HCC), but its efficacy is modest with low response rates and short response duration. Predictive biomarkers for sorafenib efficacy are necessary. However, efforts to determine biomarkers for sorafenib have led only to potential candidates rather than clinically useful predictors. Studies based on patient cohorts identified the potential of blood levels of angiopoietin-2, hepatocyte growth factor, insulin-like growth factor-1, and transforming growth factor-β1 for predicting sorafenib efficacy. Alpha-fetoprotein response, dynamic contrast-enhanced magnetic resonance imaging, and treatment-related side effects may serve as early surrogate markers. Novel approaches based on super-responders or experimental mouse models may provide new directions in biomarker research. These studies identified tumor amplification of FGF3/FGF4 or VEGFA and tumor expression of phospho-Mapk14 and phospho-Atf2 as possible predictive markers that await validation. A group effort that considers various prognostic factors and proper collection of tumor tissues before treatment is imperative for the success of future biomarker research in advanced HCC. PMID:26420960

  12. Advanced mass spectrometry-based multi-omics technologies for exploring the pathogenesis of hepatocellular carcinoma.

    PubMed

    Nie, Wenna; Yan, Leyu; Lee, Yie H; Guha, Chandan; Kurland, Irwin J; Lu, Haitao

    2016-05-01

    Hepatocellular carcinoma (HCC) is one of the primary hepatic malignancies and is the third most common cause of cancer related death worldwide. Although a wealth of knowledge has been gained concerning the initiation and progression of HCC over the last half century, efforts to improve our understanding of its pathogenesis at a molecular level are still greatly needed, to enable clinicians to enhance the standards of the current diagnosis and treatment of HCC. In the post-genome era, advanced mass spectrometry driven multi-omics technologies (e.g., profiling of DNA damage adducts, RNA modification profiling, proteomics, and metabolomics) stand at the interface between chemistry and biology, and have yielded valuable outcomes from the study of a diversity of complicated diseases. Particularly, these technologies are being broadly used to dissect various biological aspects of HCC with the purpose of biomarker discovery, interrogating pathogenesis as well as for therapeutic discovery. This proof of knowledge-based critical review aims at exploring the selected applications of those defined omics technologies in the HCC niche with an emphasis on translational applications driven by advanced mass spectrometry, toward the specific clinical use for HCC patients. This approach will enable the biomedical community, through both basic research and the clinical sciences, to enhance the applicability of mass spectrometry-based omics technologies in dissecting the pathogenesis of HCC and could lead to novel therapeutic discoveries for HCC. © 2014 Wiley Periodicals, Inc. Mass Spec Rev 35:331-349, 2016. PMID:24890331

  13. Chinese Herbal Formulation PHY906 and Sorafenib Tosylate in Treating Patients With Advanced Liver Cancer

    ClinicalTrials.gov

    2016-06-17

    Adult Primary Hepatocellular Carcinoma; Advanced Adult Primary Liver Cancer; Advanced Adult Hepatocellular Carcinoma; BCLC Stage B Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma

  14. Metronomic Capecitabine in Advanced Hepatocellular Carcinoma Patients: A Phase II Study

    PubMed Central

    de Rosa, Francesco; Agostini, Valentina; di Girolamo, Stefania; Andreone, Pietro; Bolondi, Luigi; Serra, Carla; Sama, Claudia; Golfieri, Rita; Gramenzi, Annagiulia; Cucchetti, Alessandro; Pinna, Antonio Daniele; Trevisani, Franco; Biasco, Guido

    2013-01-01

    Background. Anti-angiogenic treatment with targeted agents is effective in advanced hepatocellular carcinoma (HCC). This trial evaluated the safety and efficacy of metronomic capecitabine in patients with HCC. Methods. This single-institution phase II trial included 59 previously untreated patients with advanced HCC and 31 patients resistant to or intolerant of sorafenib. The treatment schedule was capecitabine 500 mg twice daily until progression of disease, unacceptable toxicity level, or withdrawal of informed consent. Progression-free survival (PFS) was chosen as the primary endpoint. Results. A total of 59 previously untreated and 31 previously treated patients with HCC were enrolled. The first cohort achieved a median PFS of 6.03 months and an overall survival (OS) of 14.47 months. Two patients achieved a complete response, 1 patient achieved partial response, and in 30 patients, stable disease was the best outcome. The second cohort achieved a median PFS of 3.27 months and a median OS of 9.77 months. No complete or partial responses were observed, but 10 patients had stable disease. An unscheduled comparison of the first cohort of patients with 3,027 untreated patients with HCC from the Italian Liver Cancer (ITA.LI.CA) database was performed. One-to-one matching according to demographic/etiologic/oncologic features was possible for 50 patients. The median OS for these 50 capecitabine-treated patients was 15.6 months, compared with a median OS of 8.0 months for the matched untreated patients (p = .043). Conclusion. Metronomic capecitabine is well tolerated by patients with advanced HCC and appears to have activity both in treatment-naive patients and in those previously treated with sorafenib. PMID:24232581

  15. Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma.

    PubMed

    Yang, Ke; Zhang, Xiao-Ming; Yang, Lin; Xu, Hao; Peng, Juan

    2016-05-28

    Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization (TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusion-weighted magnetic resonance imaging (MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusion-weighted imaging, blood oxygen level-dependent MRI, positron emission tomography (PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed. PMID:27239110

  16. Targeted therapy for advanced hepatocellular cancer in the elderly: focus on sorafenib.

    PubMed

    Germano, D; Tinessa, V; Barletta, E; Cannella, L; Daniele, B

    2013-11-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Worldwide progressive population aging demands consensus development for decision making when treating elderly patients. Age itself might not be a critical determinant for the selection of a therapeutic option. In the past few years, the mechanisms of hepato-carcinogenesis have been elucidated, and the involvement of a number of pathways, including angiogenesis, aberrant signal transduction, and dysregulated cell cycle control, have been demonstrated, leading to evaluation of the activity and toxicity of some of the new molecularly targeted agents. Sorafenib was demonstrated to significantly increase the survival of patients with advanced HCC in two prospective, randomized, placebo-controlled trials. Subsequently, a number of retrospective or prospective studies have indicated that the effectiveness of sorafenib therapy in the treatment of HCC is similar in elderly and non-elderly patients. The aim of this review is to describe the impact of age on the effects of sorafenib-targeted therapy in patients with HCC, and the next treatment options with new targeted agents (everolimus, tivantinib, linifanib, etc.). PMID:24097332

  17. A phase I clinical trial of thymidine kinase-based gene therapy in advanced hepatocellular carcinoma.

    PubMed

    Sangro, B; Mazzolini, G; Ruiz, M; Ruiz, J; Quiroga, J; Herrero, I; Qian, C; Benito, A; Larrache, J; Olagüe, C; Boan, J; Peñuelas, I; Sádaba, B; Prieto, J

    2010-12-01

    The aim of this phase I clinical trial was to assess the feasibility and safety of intratumoral administration of a first-generation adenoviral vector encoding herpes simplex virus thymidine kinase (HSV-TK) gene (Ad.TK) followed by systemic ganciclovir to patients with advanced hepatocellular carcinoma (HCC). Secondarily, we have analyzed its antitumor effect. Ten patients were enrolled in five dose-level cohorts that received from 10¹⁰ to 2 × 10¹² viral particles (vp). Ad.TK was injected intratumorally and patients received up to three doses at 30-day intervals. Positron emission tomography was used to monitor TK gene expression. Ad.TK injection was feasible in 100% of cases. Treatment was well tolerated and dose-limiting toxicity was not achieved. Cumulative toxicity was not observed. Hepatic toxicity was absent even in cirrhotic patients. Fever, flu-like syndrome, pain at the injection site and pancytopenia were the most common side effects. No partial responses were observed and 60% of patients showed tumor stabilization of the injected lesion. Importantly, two patients who received the highest dose showed signs of intratumoral necrosis by imaging procedures. One of them achieved a sustained stabilization and survived for 26 months. In conclusion, Ad.TK can be safely administered by intratumoral injection to patients with HCC up to 2 × 10¹² vp per patient. PMID:20689572

  18. [Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

    PubMed

    Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Matsukiyo, Yasushi; Kogame, Michio; Shinohara, Mie; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

    2016-07-01

    We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival. PMID:27431630

  19. Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma

    PubMed Central

    Yang, Ke; Zhang, Xiao-Ming; Yang, Lin; Xu, Hao; Peng, Juan

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization (TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusion-weighted magnetic resonance imaging (MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusion-weighted imaging, blood oxygen level-dependent MRI, positron emission tomography (PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed. PMID:27239110

  20. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI

    PubMed Central

    Joo, Ijin; Lee, Jeong Min

    2016-01-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  1. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI.

    PubMed

    Joo, Ijin; Lee, Jeong Min

    2016-02-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  2. Simultaneous Multitarget Irradiation Using Helical Tomotherapy for Advanced Hepatocellular Carcinoma With Multiple Extrahepatic Metastases

    SciTech Connect

    Jang, Jeong Won Kay, Chul Seung You, Chan Ran; Kim, Chang Wook; Bae, Si Hyun.; Choi, Jong Young; Yoon, Seung Kew; Han, Chi Wha; Jung, Hyun Suk; Choi, Ihl Bong

    2009-06-01

    Purpose: The prognosis of hepatocellular carcinoma (HCC) patients with extrahepatic metastases is extremely poor. Helical tomotherapy, an image-guided, intensity-modulated radiotherapy system, can allow for simultaneous and precise targeting of multiple cancerous lesions, while sparing normal tissues. This study evaluated the feasibility and outcome of tomotherapy for advanced HCC with metastases. Patients and Methods: A total of 42 consecutive HCC patients with metastases were treated with tomotherapy using the Hi-Art system. A total of 152 intra- and extrahepatic lesions (3.5 lesions/patient) were treated simultaneously, with a dose of 51.03 Gy (range, 30-57.61) in 10 fractions. Transarterial chemolipiodolization using epirubicin (50 mg) and cisplatin (60 mg) was repeated in patients with intrahepatic HCC (mean size, 9.0 cm) after tomotherapy. Results: An objective response (complete response and partial response) was achieved in 45.2% of patients with intrahepatic tumors, 68.4% of patients with pulmonary lesions, 60.0% of patients with lymph node/adrenal lesions, and 66.7% of patients with soft-tissue metastases. The complete response rate for those with pulmonary and lymph node/adrenal metastases was 26.3% and 5.0%, respectively. The overall survival rate at 1 and 2 years was 50.1% and 14.9%, respectively, with a median survival of 12.3 months. The actuarial in-field tumor control rate for {<=}1 year was 79.0%. No cases of Grade 4-5 acute toxicity occurred. Conclusion: The results of this study have shown that helical tomotherapy is safe and feasible without major toxicities for the treatment of advanced HCC and results in excellent tumor control and a potential survival benefit. This approach is expected to be a useful palliative option for selected HCC patients with metastases.

  3. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

  4. High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis.

    PubMed

    Oh, Bong-Kyeong; Kim, Haeryoung; Park, Young Nyun; Yoo, Jeong Eun; Choi, Jinsub; Kim, Kyung-Sik; Lee, Jae Jung; Park, Chanil

    2008-02-01

    Telomerase reactivation and telomere maintenance are crucial in carcinogenesis and tumor progression. In this study, the relationships between telomere parameters, chromosomal instability and clinicopathological features were evaluated in hepatocellular carcinomas (HCCs). Telomere length (TL), telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA levels were measured in 49 hepatitis B virus (HBV)-related HCCs and corresponding non-tumorous tissues. The results were compared with clinicopathological data, including differentiation, multipolar mitosis (MM), anaphase bridge, immunohistochemical stain results for cytokeratin 19 (CK19) and patient outcome. TL of HCCs ranged from 4.7 to 13.1 kb, and 44.4% of HCCs showed telomere lengthening. hTERT mRNA levels and TA were closely related (P=0.008), and were significantly higher in HCCs than non-tumorous tissues. TL was significantly higher in HCCs with strong TA (P=0.048), high hTERT mRNA levels (P=0.001) and poor differentiation (P=0.041). Frequent MM was associated with poor differentiation (P=0.007) and advanced stage (P<0.001). TA was positively correlated with MM, anaphase bridges and advanced stage (P=0.019, P=0.017 and P=0.029). Thirteen (28.3%) HCCs were CK19+ and demonstrated longer telomeres than CK19- HCCs (P=0.046). Overall survival was poor in HCCs with MM >0.4 per field (P=0.016), high TA (P=0.009) and high TL ratio (HCC/non-HCC) >0.8 (P=0.044). Our results show that long telomeres, high TA and high mitotic instability are poor prognostic markers for HBV-related HCCs and their close association suggests that telomere maintenance may be important for the progression of HCCs with high chromosomal instability to more aggressive ones. PMID:18158557

  5. Determinants of esophageal varices bleeding in patients with advanced hepatocellular carcinoma treated with sorafenib

    PubMed Central

    Iavarone, Massimo; Primignani, Massimo; Vavassori, Sara; Sangiovanni, Angelo; La Mura, Vincenzo; Romeo, Raffaella

    2015-01-01

    Background and aims Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC), yet treatment safety may be challenged by portal hypertension. We therefore assessed the prevalence, risk factors and clinical consequences of esophageal varices (EVs) in sorafenib-treated patients with HCC. Methods Starting in 2008, all compensated patients with advanced or intermediate HCC not eligible for other therapies were consecutively enrolled in a prospective evaluation of sorafenib therapy, all with pretreatment by upper-gastrointestinal endoscopy (UGE). Results A total of 150 patients received sorafenib for 4.6 (95% CI, 3.3–5.6) months. At baseline, 61 (41%) patients were EV free (group A), 78 (52%) had EVs (61 small EVs (group B), 17 medium/large EVs (group C)) and 11 (7%) previously endoscopically treated EVs (group D). Propranolol was given to all patients with medium/large EVs and those with previous bleeding. Twelve patients (8%) bled from EVs after 36 (18–260) days of sorafenib. During sorafenib, bleeding occurred in six of 26 group B patients with neoplastic portal vein thrombosis (nPVT), three of nine group C patients with nPVT, two of five group D patients with nPVT and one of six without nPVT (p < 0.0001), nPVT being the strongest independent predictor of bleeding by multivariate analysis (HR = 15.4, 95% CI 1.84–129.6). Conclusion UGE screening is worthwhile in HCC patients allocated to sorafenib since it identifies patients with EVs at risk of bleeding during therapy, particularly those with nPVT.

  6. [Survival after Sorafenib Treatment for Advanced Recurrent Hepatocellular Carcinoma with Tumor Thrombus in the Inferior Vena Cava].

    PubMed

    Matoba, Hideaki; Seta, Shinsuke

    2015-11-01

    A 72-year-old man with chronic viral hepatitis type B undergoing surgery for hepatocellular carcinoma was found to have a recurrent tumor in the left liver with peritoneal dissemination near the inferior vena cava(IVC)and tumor thrombus in the IVC. For this patient diagnosed with Barcelona clinic liver cancer (BCLC) classification stage C hepatocellular carcinoma, we initiated 800 mg/body sorafenib. Two weeks after the initiation of sorafenib, the patient experienced grade 3 hand-foot syndrome, after which, the dose of sorafenib was reduced to 400 mg/body. After 1 year, CT showed an enlarged tumor in the left liver and multiple metastases to the lung. However, no remarkable difference was observed in the peritoneal dissemination and the tumor thrombus. He has been receiving sorafenib for 19 months with a good quality of life. Sorafenib can be provided on an outpatient basis and it may facilitate long-term survival for patients with advanced recurrent hepatocellular carcinoma with IVC tumor thrombus. This clinical condition is very rare, and the standard treatment for it still has not been established. PMID:26805098

  7. Advances and Challenges in Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Smith, J. Joshua; Garcia-Aguilar, Julio

    2015-01-01

    Dramatic improvements in the outcomes of patients with rectal cancer have occurred over the past 30 years. Advances in surgical pathology, refinements in surgical techniques and instrumentation, new imaging modalities, and the widespread use of neoadjuvant therapy have all contributed to these improvements. Several questions emerge as we learn of the benefits or lack thereof for components of the current multimodality treatment in subgroups of patients with nonmetastatic locally advanced rectal cancer (LARC). What is the optimal surgical technique for distal rectal cancers? Do all patients need postoperative chemotherapy? Do all patients need radiation? Do all patients need surgery, or is a nonoperative, organ-preserving approach warranted in selected patients? Answering these questions will lead to more precise treatment regimens, based on patient and tumor characteristics, that will improve outcomes while preserving quality of life. However, the idea of shifting the treatment paradigm (chemoradiotherapy, total mesorectal excision, and adjuvant therapy) currently applied to all patients with LARC to a more individually tailored approach is controversial. The paradigm shift toward organ preservation in highly selected patients whose tumors demonstrate clinical complete response to neoadjuvant treatment is also controversial. Herein, we highlight many of the advances and resultant controversies that are likely to dominate the research agenda for LARC in the modern era. PMID:25918296

  8. Survival Benefit of Locoregional Treatment for Hepatocellular Carcinoma with Advanced Liver Cirrhosis

    PubMed Central

    Kitai, Satoshi; Kudo, Masatoshi; Nishida, Naoshi; Izumi, Namiki; Sakamoto, Michiie; Matsuyama, Yutaka; Ichida, Takafumi; Nakashima, Osamu; Matsui, Osamu; Ku, Yonson; Kokudo, Norihiro; Makuuchi, Masatoshi

    2016-01-01

    Background & Aims Hepatocellular carcinoma (HCC) with decompensated liver cirrhosis (LC) is a life-threatening condition, which is amenable to liver transplantation (LT) as the standard first-line treatment. However, the application of LT can be limited due to a shortage of donor livers. This study aimed to clarify the effect of non-surgical therapy on the survival of patients with HCC and decompensated LC. Methods Of the 58,886 patients with HCC registered in the nationwide survey of the Liver Cancer Study Group of Japan (January 2000-December 2005), we included 1,344 patients with primary HCC and Child-Pugh (C-P) grade C for analysis in this retrospective study. Among the patients analyzed, 108 underwent LT, 273 were treated by local ablation therapy (LAT), 370 were treated by transarterial chemoembolization (TACE), and 593 received best supportive care (BSC). The effect of LT, LAT, and TACE on overall survival (OS) was analyzed using multivariate and propensity score analyses. Results Patient characteristics did not differ significantly between each treatment group and the BSC group, after propensity score matching. LAT (hazard ratio [HR]) =0.568; 95% confidence interval [CI], 0.40-0.80) and TACE (HR=0.691; 95% CI, 0.50-0.96) were identified as significant contributors to OS if the C-P score was less than 11 and tumor conditions met the Milan criteria. Conclusions For patients with HCC within the Milan criteria and with a C-P score of 10 or 11, locoregional treatment can be used as a salvage treatment if LT is not feasible. PMID:27493893

  9. Phase I Study of Lenalidomide and Sorafenib in Patients With Advanced Hepatocellular Carcinoma

    PubMed Central

    Loehrer, Patrick J.; Clark, Romnee S.; Spittler, A. John; Althouse, Sandra K.; Chiorean, E. Gabriella

    2016-01-01

    Lessons Learned Combination therapies in patients with hepatocellular carcinoma can be associated with overlapping toxicity and are therefore poorly tolerated. Using sorafenib at the maximum tolerated dose can lead to a higher incidence of toxicities. Consequently, combination studies might evaluate sorafenib at alternative schedules or doses to improve tolerance, recognizing this could affect sorafenib efficacy. Although this combination was poorly tolerated, it does not exclude further evaluation of new-generation immunomodulator drugs or immune checkpoint inhibitors in the hope of optimizing tolerance and safety. Background. Sorafenib is the standard treatment for advanced hepatocellular carcinoma (HCC), and to date, no combination therapy has demonstrated superior survival compared with sorafenib alone. The immunosuppressive microenvironment in HCC is a negative predictor for survival. Lenalidomide is an immunomodulator and antiangiogenic agent, with limited single-agent efficacy in HCC. Based on these data, we designed a phase I study of sorafenib plus lenalidomide to determine the safety and preliminary antitumor activity of this combination. Methods. This was an open-label, phase I study with a 3+3 dose escalation/de-escalation design. The starting dose of sorafenib was 400 mg p.o. b.i.d. and of lenalidomide was 15 mg p.o. daily with a planned dose escalation by 5 mg per cohort up to 25 mg daily. Dose de-escalation was planned to a sorafenib dose of 400 mg p.o. daily combined with two doses of lenalidomide: 10 mg p.o. daily for a 28-day cycle (cohort 1) and 10 mg p.o. daily for a 21- or 28-day cycle (cohort 2). Patients with cirrhosis, a Child-Pugh score of A-B7, and no previous systemic therapy were eligible. Results. Five patients were enrolled. Their median age was 56 years (range 39–61), and the ECOG status was 0–2. Four patients were treated at dose level (DL) 1. Because of the poor tolerance to the combination associated with grade 2 toxicities

  10. Advanced information processing system: Local system services

    NASA Technical Reports Server (NTRS)

    Burkhardt, Laura; Alger, Linda; Whittredge, Roy; Stasiowski, Peter

    1989-01-01

    The Advanced Information Processing System (AIPS) is a multi-computer architecture composed of hardware and software building blocks that can be configured to meet a broad range of application requirements. The hardware building blocks are fault-tolerant, general-purpose computers, fault-and damage-tolerant networks (both computer and input/output), and interfaces between the networks and the computers. The software building blocks are the major software functions: local system services, input/output, system services, inter-computer system services, and the system manager. The foundation of the local system services is an operating system with the functions required for a traditional real-time multi-tasking computer, such as task scheduling, inter-task communication, memory management, interrupt handling, and time maintenance. Resting on this foundation are the redundancy management functions necessary in a redundant computer and the status reporting functions required for an operator interface. The functional requirements, functional design and detailed specifications for all the local system services are documented.

  11. Multimodal therapy in locally advanced breast carcinoma

    SciTech Connect

    Lopez, M.J.; Andriole, D.P.; Kraybill, W.G.; Khojasteh, A. )

    1990-12-01

    Among 879 patients treated for breast cancer between 1975 and 1984, advanced disease was found in 125 (14%). A subgroup of 34 (4%) presented with untreated locally advanced disease without demonstrable distant metastases at the time of diagnosis (stage IIIB = T4abed, NX-2,MO). During the first 5 years (1975 through 1979), 17 patients were treated primarily with sequential radiotherapy and chemotherapy (Group A). From 1980 to 1984 (Group B), the management consisted of four courses of induction multi-drug chemotherapy followed primarily by mastectomy and additional chemotherapy. The mean follow-up for the most recent group (Group B) is 48 months. Follow-up was complete. While the local disease control rate was the same for both groups (76%), the survival was remarkably different. Group A patients experienced a median survival of 15 months, and only one survived 5 years. In Group B, the median survival was 56 months with nine patients (53%) alive between 40 and 76 months, seven (41%) of whom are 5-year survivors. While the overall mortality of patients with inflammatory breast cancer was greater in both groups when compared with the group with noninflammatory disease, the survival of patients in Group B was better than in Group A for both inflammatory and noninflammatory cancers (p less than 0.01). Estrogen receptor, nodal, and menopausal status did not influence survival. These data suggest that neoadjuvant chemotherapy improves survival for patients with stage IIIB breast carcinoma and delays the establishment or progression of distant metastases. Mastectomy is an important component in the treatment of this disease.

  12. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

    PubMed

    Cebon, J; Findlay, M; Hargreaves, C; Stockler, M; Thompson, P; Boyer, M; Roberts, S; Poon, A; Scott, A M; Kalff, V; Garas, G; Dowling, A; Crawford, D; Ring, J; Basser, R; Strickland, A; Macdonald, G; Green, M; Nowak, A; Dickman, B; Dhillon, H; Gebski, V

    2006-10-01

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways. PMID:16953241

  13. Protrusion-localized STAT3 mRNA promotes metastasis of highly metastatic hepatocellular carcinoma cells in vitro

    PubMed Central

    Liu, Yan-hong; Jin, Jia-lu; Wang, Yu-zhe; Tan, Ying; Zhou, Ying-ying; Peng, Ting; Li, Feng; Liang, Wan-dong; Chartrand, Pascal; Jiang, Yu-yang; Shen, Zhi-fa

    2016-01-01

    Aim: Recent evidence shows that localization of mRNAs and their protein products at cellular protrusions plays a decisive function in the metastasis of cancer cells. The aim of this study was to identify the variety of proteins encoded by protrusion-localized mRNAs and their roles in the metastasis and invasion of liver cancer cells. Methods: Highly metastatic hepatocellular carcinoma cell line HCCLM3 and non-metastatic hepatocellular carcinoma cell line SMMC-7721 were examined. Cell protrusions (Ps) were separated from cell bodies (CB) using a Boyden chamber assay; total mRNA population in CB and Ps fractions was analyzed using high-throughput direct RNA sequencing. The localization of STAT3 mRNA and protein at Ps was confirmed using RT-qPCR, RNA FISH, and immunofluorescence assays. Cell migration capacity and invasiveness of HCCLM3 cells were evaluated using MTT, wound healing migration and in vitro invasion assays. The interaction between Stat3 and growth factor receptors was explored with co-immunoprecipitation assays. Results: In HCCLM3 cells, 793 mRNAs were identified as being localized in the Ps fraction according to a cut-off value (Ps/CB ratio) >1.6. The Ps-localized mRNAs could be divided into 4 functional groups, and were all closely related to the invasive and metastatic properties. STAT3 mRNA accumulated in the Ps of HCCLM3 cells compared with non-metastatic SMMC-7721 cells. Treatment of HCCLM3 cells with siRNAs against STAT3 mRNA drastically decreased the cell migration and invasion. Moreover, Ps-localized Stat3 was found to interact with pseudopod-enriched platelet-derived growth factor receptor tyrosine kinase (PDGFRTK) in a growth factor-dependent manner. Conclusion: This study reveals STAT3 mRNA localization at the Ps of metastatic hepatocellular carcinoma HCCLM3 cells by combining application of genome-wide and gene specific description and functional analysis. PMID:27133294

  14. Long-term outcomes of patients with advanced hepatocellular carcinoma who achieved complete remission after sorafenib therapy

    PubMed Central

    2015-01-01

    Background/Aims Sorafenib is currently the sole molecular targeted agent that improves overall survival in advanced hepatocellular carcinoma (HCC). Despite the efficacy of sorafenib, the response rate varies in patients with advanced HCC. We retrospectively analyzed a series of Korean patients with advanced HCC with complete remission (CR) after sorafenib therapy. Methods In total, 523 patients with advanced HCC were treated with sorafenib in 3 large tertiary referral hospitals in Korea. A survey was conducted to collect data on patients who experienced CR after sorafenib monotherapy, and their medical records and follow-up data were analyzed. The tumor response and recurrence rates were assessed by radiologic study, based on modified response evaluation criteria in solid tumors. Results Seven patients with advanced HCC experienced CR after sorafenib therapy. The median time to tumor disappearance and the median disease-free survival time were 3 months and 9 months, respectively. HCC recurrence was identified in three cases (42.9%). Of these, two patients discontinued sorafenib before or after achieving CR and the other patient continued sorafenib after achieving CR. HCC recurred at 3, 10, and 42 months after CR in these three patients. Three patients needed dose reduction for toxicity and adverse events. Conclusions Though CR was achieved after sorafenib therapy in patients with advanced HCC, the recurrence rate was relatively high. Subsequent strategies to reduce a chance of recurrence after sorafenib therapy are required to investigate. PMID:26527250

  15. New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions.

    PubMed

    Chuma, Makoto; Terashita, Katsumi; Sakamoto, Naoya

    2015-10-01

    Hepatocellular carcinoma (HCC) can be lethal due to its aggressive course and lack of effective systemic therapies for advanced disease. Sorafenib is the only systemic therapy that has demonstrated an overall survival benefit in patients with advanced HCC, and new agents for treatment of advanced HCC are needed. The multiple pathways involved in HCC oncogenesis, proliferation and survival provide many opportunities for the development of molecularly targeted therapies. Molecular targets of interest have expanded from angiogenesis to cancer cell-directed oncogenic signaling pathways for treatment of advanced HCC. Agents targeting vascular endothelial growth factor receptor, epidermal growth factor receptor, fibroblast growth factor receptor, platelet-derived growth factor receptor, c-mesenchymal-epithelial transition factor-1 and mammalian target of rapamycin signaling have been actively explored. This article focuses on the evaluation of molecular agents targeting pathogenic HCC and provides a review of recently completed phase III drug studies (e.g. involving sorafenib, sunitinib, brivanib, linifanib, erlotinib, everolimus, ramucirumab or orantinib) and ongoing drug studies (e.g. involving lenvatinib, regorafenib, tivantinib or cabozantinib) of molecularly targeted agents in advanced HCC, including a brief description of the biologic rationale behind these agents. PMID:25472913

  16. Radioembolization using 90Y-resin microspheres for patients with advanced hepatocellular carcinoma

    SciTech Connect

    Sangro, Bruno . E-mail: bsangro@unav.es; Bilbao, Jose I.; Boan, Jose; Martinez-Cuesta, Antonio; Benito, Alberto; Rodriguez, Javier; Panizo, Angel; Gil, Belen; Inarrairaegui, Mercedes; Herrero, Ignacio; Quiroga, Jorge; Prieto, Jesus

    2006-11-01

    Purpose: To investigate the antitumor effect of resin microspheres loaded with 90-yttrium against hepatocellular carcinoma and their safety in the setting of liver cirrhosis. Patients and Methods: Data from 24 consecutive patients with hepatocellular carcinoma (HCC) treated by radioembolization in the period from September 2003 to February 2005 were reviewed. Patients received no further antineoplastic therapy. A comprehensive evaluation was performed to prevent the risk of damage due to microsphere misplacing. Patients were discharged the day after microspheres injection. Results: Serious liver toxicity observed among cirrhotic patients in a first period was subsequently prevented by modifying the selection criteria and the method for calculating the activity to be administered. Among 21 patients evaluable for response using Response Evaluation Criteria in Solid Tumors (RECIST) criteria, a reduction in size of target lesions was observed in all but 1 patient. When considering only target lesions, disease control rate and response rate were 100% and 23.8%, respectively. However, 43% of patients progressed in the liver in the form of new lesions appearing a median time of 3 months after radioembolization. Conclusion: Our experience in these series of patients indicates that radioembolization using resin microspheres has a significant antitumor effect against HCC and that using stringent selection criteria and conservative models for calculating Radiation activity to be administered, radioembolization can be performed safely even in cirrhotic patients.

  17. Percutaneous Radiofrequency Ablation and Transcatheter Arterial Chemoembolization for Hypervascular Hepatocellular Carcinoma: Rate and Risk Factors for Local Recurrence

    SciTech Connect

    Murakami, Tomonori Ishimaru, Hideki; Sakamoto, Ichiro; Uetani, Masataka; Matsuoka, Yohjiro; Daikoku, Manabu; Honda, Sumihisa; Koshiishi, Takeshi; Fujimoto, Toshifumi

    2007-07-15

    Purpose. To analyze local recurrence-free rates and risk factors for recurrence following percutaneous radiofrequency ablation (RFA) or transcatheter arterial chemoembolization (TACE) for hypervascular hepatocellular carcinoma (HCC). Methods. One hundred and nine nodules treated by RFA and 173 nodules treated by TACE were included. Hypovascular nodules were excluded from this study. Overall local recurrence-free rates of each treatment group were calculated using the Kaplan-Meier method. The independent risk factors of local recurrence and the hazard ratios were analyzed using Cox's proportional-hazards regression model. Based on the results of multivariate analyses, we classified HCC nodules into four subgroups: central nodules {<=}2 cm or >2 cm and peripheral nodules {<=}2 cm or >2 cm. The local recurrence-free rates of these subgroups for each treatment were also calculated. Results. The overall local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p = 0.013). The 24-month local recurrence-free rates in the RFA and TACE groups were 60.0% and 48.9%, respectively. In the RFA group, the only significant risk factor for recurrence was tumor size >2 cm in greatest dimension. In the TACE group, a central location was the only significant risk factor for recurrence. In central nodules that were {<=}2 cm, the local recurrence-free rate was significantly higher in the RFA group than in the TACE group (p < 0.001). In the remaining three groups, there was no significant difference in local recurrence-free rate between the two treatment methods. Conclusion. A tumor diameter of >2 cm was the only independent risk factor for local recurrence in RFA treatment, and a central location was the only independent risk factor in TACE treatment. Central lesions measuring {<=}2 cm should be treated by RFA.

  18. A Phase I Dose-Finding Study of Silybin Phosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma

    PubMed Central

    Siegel, Abby B.; Narayan, Rupa; Rodriguez, Rosa; Goyal, Abhishek; Jacobson, Judith S.; Kelly, Kara; Ladas, Elena; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Flaig, Thomas W.; Tsai, Wei Yann; Wu, David P. H.; Lee, Valerie; Greenlee, Heather

    2013-01-01

    Purpose To determine the maximum tolerated dose per day of silybin phosphatidylcholine (Siliphos) in patients with advanced hepatocellular carcinoma (HCC) and hepatic dysfunction. Experimental Design Patients with advanced HCC not eligible for other therapies based on poor hepatic function were enrolled in a phase I study of silybin phosphatidylcholine. A standard phase I design was used with 4 planned cohorts, dose escalating from 2, 4, 8, to 12 g per day in divided doses for 12 weeks. Results Three participants enrolled in this single institution trial. All enrolled subjects consumed 2 g per day of study agent in divided doses. Serum concentrations of silibinin and silibinin glucuronide increased within 1 to 3 weeks. In all 3 patients, liver function abnormalities and tumor marker α-fetoprotein progressed, but after day 56 the third patient showed some improvement in liver function abnormalities and inflammatory biomarkers. All 3 participants died within 23 to 69 days of enrolling into the trial, likely from hepatic failure, but it could not be ruled out that deaths were possibly due to the study drug. Conclusion Short-term administration of silybin phosphatidylcholine in patients with advanced HCC resulted in detectable increases in silibinin and its metabolite, silibinin glucuronide. The maximum tolerated dose could not be established. Since patients died soon after enrollment, this patient population may have been too ill to benefit from an intervention designed to improve liver function tests. PMID:23757319

  19. The systemic inflammatory response as a prognostic factor for advanced hepatocellular carcinoma with extrahepatic metastasis

    PubMed Central

    AINO, HAJIME; SUMIE, SHUJI; NIIZEKI, TAKASHI; KUROMATSU, RYOKO; TAJIRI, NOBUYOSHI; NAKANO, MASAHITO; SATANI, MANABU; OKAMURA, SHUSUKE; SHIMOSE, SHIGEO; MIYAHARA, KENSUKE; TORIMURA, TAKUJI

    2016-01-01

    Several indices have been proposed to evaluate the systemic inflammatory response (SIR), which has been reported to be a useful prognostic factor in various types of cancer. We investigated the usefulness of the Glasgow Prognostic Score (GPS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with advanced hepatocellular carcinoma (HCC) with extrahepatic metastasis (stage IVB). Between April, 1997 and March, 2013, a total of 434 HCC patients who developed extrahepatic metastasis were enrolled in the present study. The GPS was defined on the basis of pretreatment C-reactive protein (CRP) and albumin (Alb) levels, and the subjects were grouped according to GPS 0–2. The NLR was calculated as the neutrophil count/lymphocyte count, and the PLR was calculated as the platelet count/lymphocyte count. A comparative examination was performed using a survival analysis with approximate median values to determine the cut-off value for both ratios. The median survival time (MST) of the 434 patients overall was 7.3 months, with cumulative survival rates of 31.8, 14.5 and 7.7% at 1, 2 and 3 years, respectively. The patient backround was as follows: The male:female ratio was 363:71, with a median age of 67.0 years (range, 15.0–92.0 years). Hepatitis B virus patients:hepatitis C virus patients:non-B, non-C hepatitis patients = 75:303:56. Child-Pugh class A:B:C = 218:153:63. As regards T stage, ≤T2:T3:T4 = 60:190:181. The median white blood cell count was 4,650/l (range, 1,400-20,500/l); the platelet count was 11.1×104/µl (range, 3.1×104-45.5×104/µl); the aspartate aminotransferase level was 40.0 U/l (range, 7.0–338.0 U/l) and the alanine aminotransferase level 64.5 U/l (range, 16.0–407.0 U/l); the α-fetoprotein level was 622.1 ng/ml (range, 1.5–3,311,794.0 ng/ml); and the des-gamma-carboxyprothrombin level was 1,285.0 mAU/ml (range, 8.0->75,000 mAU/ml). The principal sites of metastasis included the lungs

  20. Surgical adjuvant treatment of locally advanced breast cancer.

    PubMed Central

    Townsend, C M; Abston, S; Fish, J C

    1985-01-01

    The reported incidence of local recurrence after mastectomy for locally advanced breast cancer (TNM Stage III and IV) is between 30% and 50%. The purpose of this study was to evaluate the effect of radiation therapy (XRT) followed by total mastectomy on the incidence of local recurrence in patients with locally advanced breast cancer. Fifty-three patients who presented with locally advanced breast cancer, without distant metastases, were treated with XRT (4500-5000 R) to the breast, chest wall, and regional lymph nodes. Five weeks after completion of XRT, total mastectomy was performed. There were no operative deaths. The complications that occurred in 22 patients after surgery were flap necrosis, wound infection, and seroma. Patients have been followed from 3 to 134 months. Twenty-five patients are alive (3-134 months), 12 free of disease; 28 patients have died with distant metastases (6-67 months). Isolated local recurrence occurred in only two patients. Four patients had local and distant recurrence (total local recurrence is 6/53). The remaining patients all developed distant metastases. We have devised a treatment strategy which significantly decreases the incidence of local recurrence in patients with locally advanced breast cancer. However, the rapid appearance of distant metastases emphasizes the need for systemically active therapy in patients with locally advanced breast cancer. PMID:3994434

  1. Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition.

    PubMed

    Finn, Richard S

    2012-11-01

    Hepatocellular carcinoma (HCC) is a common cancer that has the third highest cancer-related mortality rate worldwide. Although potentially curable by transplantation if detected early, the majority of cases are diagnosed at an advanced stage of disease for which limited treatment options are available. The only proven systemic therapy for advanced HCC is sorafenib, a multi-kinase inhibitor that has demonstrated modest efficacy and reasonable tolerability in patients with advanced HCC. Five years after the approval of sorafenib, no other agent has been proven to be beneficial in the first- or second-line setting in advanced HCC. While molecular studies have highlighted various potential targets in HCC, the mammalian target of rapamycin (mTOR) has emerged as an exciting target for cancer therapy including HCC. Laboratory data have linked the phosphatidylinositol 3-kinase/AKT/mTOR axis to various oncogenic processes, including survival and angiogenesis. Historically, mTOR inhibitors have been used for their immunosuppressive properties, but more recently they have been approved as anticancer agents. Retrospective HCC studies suggest that the inclusion of mTOR inhibition as part of an immunosuppressant regimen after transplantation may reduce HCC recurrence compared with other immunosuppressive agents such as calcineurin inhibitors. More recently, single-arm, phase I/II studies have shown that mTOR inhibitors also have activity as monotherapy in cases of recurrent HCC or de novo advanced HCC. This article will review the rationale for targeting the mTOR pathway in HCC, and the currently available clinical data supporting its development for HCC. PMID:24159589

  2. Multicentre phase II trial of capecitabine plus oxaliplatin (XELOX) in patients with advanced hepatocellular carcinoma: FFCD 03-03 trial

    PubMed Central

    Boige, V; Raoul, J-L; Pignon, J-P; Bouché, O; Blanc, J-F; Dahan, L; Jouve, J-L; Dupouy, N; Ducreux, M

    2007-01-01

    Evaluation of new drug combinations is needed to improve patients' prognosis in advanced hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the safety and efficacy of the capecitabine–oxaliplatine combination (XELOX) in HCC patients. First-line chemotherapy with XELOX regimen consisting of a 3-week cycle of intravenous oxaliplatin (130 mg m−2) on Day 1, and oral capecitabine twice daily from Days 1–14 (1000 mg m−2) was administered in patients with measurable, unresectable HCC. Fifty patients (male, 88%; median age, 68 years) received a total of 295 cycles (median, 6) of treatment. Disease control (three partial responses, 29 stable diseases) rate was 72% (95% CI 57–83%). Median overall and median progression-free (PFS) survival was 9.3 months and 4.1 months, respectively. Progression-free survival rates at 6 and 12 months were 38% (95% CI 26–52%) and 14% (95% CI 7–26%), respectively. Main grade 3–4 drug-related toxicities included diarrhoea (16%), elevation of aminotransferases and/or bilirubin (16%), thrombocytopenia (12%), and neurotoxicity (6%). Capecitabine plus oxaliplatin regimen showed modest anti-tumour activity with tolerable toxicities in patients with advanced HCC. However, the manageable toxicity profile and the encouraging disease control rate deserve further attention for this convenient, outpatient-based chemotherapy regimen. PMID:17876335

  3. Rapid long-lasting biochemical and radiological response to sorafenib in a case of advanced hepatocellular carcinoma.

    PubMed

    Gerardi, Assunta Maria Teresa; Stoppino, Luca Pio; Liso, Arcangelo; Macarini, Luca; Landriscina, Matteo

    2013-03-01

    The multikinase inhibitor sorafenib has demonstrated an overall survival benefit in phase III hepatocellular carcinoma (HCC) trials and has become the new standard of care for advanced stages of this disease. However, in clinical practice, the vast majority of patients obtain disease stabilization and occasionally tumor shrinkage. Furthermore, the appropriate timing of sorafenib therapy initiation, in order to maximize its clinical activity, remains under debate. We report a case of 4-year sorafenib treatment in a patient with an advanced hepatitis C virus (HCV)-related HCC with extensive infiltration of the inferior vena cava. Sorafenib treatment induced a rapid complete biochemical response and a long-term favorable outcome. Additionally, no major toxicities or detrimental effects on quality of life were observed. Thus, it is likely that a subgroup of human HCC may be highly sensitive to sorafenib; new molecular determinants are required to select those patients who may benefit from this therapy. Furthermore, a prompt initiation of treatment when the hepatic function is not compromised is a prerequisite for maximizing the clinical activity of sorafenib. PMID:23426789

  4. Rapid long-lasting biochemical and radiological response to sorafenib in a case of advanced hepatocellular carcinoma

    PubMed Central

    GERARDI, ASSUNTA MARIA TERESA; STOPPINO, LUCA PIO; LISO, ARCANGELO; MACARINI, LUCA; LANDRISCINA, MATTEO

    2013-01-01

    The multikinase inhibitor sorafenib has demonstrated an overall survival benefit in phase III hepatocellular carcinoma (HCC) trials and has become the new standard of care for advanced stages of this disease. However, in clinical practice, the vast majority of patients obtain disease stabilization and occasionally tumor shrinkage. Furthermore, the appropriate timing of sorafenib therapy initiation, in order to maximize its clinical activity, remains under debate. We report a case of 4-year sorafenib treatment in a patient with an advanced hepatitis C virus (HCV)-related HCC with extensive infiltration of the inferior vena cava. Sorafenib treatment induced a rapid complete biochemical response and a long-term favorable outcome. Additionally, no major toxicities or detrimental effects on quality of life were observed. Thus, it is likely that a subgroup of human HCC may be highly sensitive to sorafenib; new molecular determinants are required to select those patients who may benefit from this therapy. Furthermore, a prompt initiation of treatment when the hepatic function is not compromised is a prerequisite for maximizing the clinical activity of sorafenib. PMID:23426789

  5. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model

    PubMed Central

    Vinh, Nguyen Quoc; Naka, Shigeyuki; Cabral, Horacio; Murayama, Hiroyuki; Kaida, Sachiko; Kataoka, Kazunori; Morikawa, Shigehiro; Tani, Tohru

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC. PMID:26203241

  6. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model.

    PubMed

    Vinh, Nguyen Quoc; Naka, Shigeyuki; Cabral, Horacio; Murayama, Hiroyuki; Kaida, Sachiko; Kataoka, Kazunori; Morikawa, Shigehiro; Tani, Tohru

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA) and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexane)platinum(II) (DACHPt)] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or saline controls. Our results suggest that Gd-DTPA/DACHPt-loaded micelles are a promising approach for effective diagnosis and treatment of advanced HCC. PMID:26203241

  7. Radical Prostatectomy for Locally Advanced Prostate Cancer: Current Status.

    PubMed

    Faria, Eliney F; Chapin, Brian F; Muller, Roberto L; Machado, Roberto D; Reis, Rodolfo B; Matin, Surena F

    2015-07-01

    In the past, prostate cancer (PC) could only be detected clinically, and delayed diagnosis of locally advanced or metastatic disease at presentation was common. Prostate-specific antigen testing and magnetic resonance imaging led to PC detection in a much earlier stage. However, controversy about the best treatment for locally advanced PC remains. Recent refinements in surgery and radiation therapy have improved outcomes, but no comparative study has yet conclusively determined superiority of one option over the other. In this review, we present the most recent evidence about the role of radical prostatectomy for locally advanced PC treatment from a surgeon's perspective. PMID:26048432

  8. Molecular mechanism by which acyclic retinoid induces nuclear localization of transglutaminase 2 in human hepatocellular carcinoma cells

    PubMed Central

    Shrestha, R; Tatsukawa, H; Shrestha, R; Ishibashi, N; Matsuura, T; Kagechika, H; Kose, S; Hitomi, K; Imamoto, N; Kojima, S

    2015-01-01

    Nuclear accumulation of transglutaminase 2 (TG2) is an important step in TG2-dependent cell death. However, the underlying molecular mechanisms for nuclear translocation of TG2 are still poorly understood. In this study, we demonstrated that acyclic retinoid (ACR) induced nuclear accumulation of TG2 in JHH-7 cells, a hepatocellular carcinoma (HCC) leading to their apoptosis. We further demonstrated molecular mechanism in nuclear-cytoplasmic trafficking of TG2 and an effect of ACR on it. We identified a novel 14-amino acid nuclear localization signal (NLS) 466AEKEETGMAMRIRV479 in the ‘C' domain and a leucine-rich nuclear export signal (NES) 657LHMGLHKL664 in the ‘D' domain that allowed TG2 to shuttle between the nuclear and cytosolic milieu. Increased nuclear import of GAPDH myc-HIS fused with the identified NLS was observed, confirming its nuclear import ability. Leptomycin B, an inhibitor of exportin-1 as well as point mutation of all leucine residues to glutamine residues in the NES of TG2 demolished its nuclear export. TG2 formed a trimeric complex with importin-α and importin-β independently from transamidase activity which strongly suggested the involvement of a NLS-based translocation of TG2 to the nucleus. ACR accelerated the formation of the trimeric complex and that may be at least in part responsible for enhanced nuclear localization of TG2 in HCC cells treated with ACR. PMID:26633708

  9. Refining Preoperative Therapy for Locally Advanced Rectal Cancer

    Cancer.gov

    In the PROSPECT trial, patients with locally advanced, resectable rectal cancer will be randomly assigned to receive either standard neoadjuvant chemoradiation therapy or neoadjuvant FOLFOX chemotherapy, with chemoradiation reserved for nonresponders.

  10. Use Of Yttrium-90 Microspheres In Patients With Advanced Hepatocellular Carcinoma & Portal Vein Thrombosis

    PubMed Central

    Tsai, Andrea L.; Burke, Charles T.; Kennedy, Andrew S.; Moore, Dominic T.; Mauro, Matthew A.; Dixon, Robert D.; Stavas, Joseph M.; Bernard, Stephen A.; Khandani, Amir H.; O'Neil, Bert H.

    2010-01-01

    Purpose Patients with portal vein thrombosis (PVT) and hepatocellular carcinoma (HCC) have limited treatment options due to increased disease burden and diminished hepatic perfusion. 90Y-microspheres may be better tolerated than chemoembolization in these patients. Here we review the safety and efficacy of 90Y-microsphere use for HCC with major PVT. Materials and Methods A retrospective review of HCC with main (n=10) or first (n=12) branch PVT treated with 90Y-microspheres (n=22) was conducted. CLIP scores ranged from 2 to 5 with 18% scoring 4 or greater. Response was determined 8-12 weeks following treatment using magnetic resonance or computed tomography and RECIST criteria. Overall survival was estimated by the Kaplan-Meier method. Results 32 treatments (26 glass, 6 resin) were administered to 22 patients. Common grade 1–2 toxicities included abdominal pain (38%), nausea (28%), fatigue (22%). Four post-therapy hospitalizations occurred, all <48hrs in duration. 1 death occurred 10 days following therapy Response data: 2 partial responses, progressive disease 42%, stable disease 50% of treatments. Median overall survival (OS) was 7 months from time of initial 90Y-microsphere treatment. Child-Pugh A patients had a median OS of 7.7 months; B and C = 2.7 months (p = 0.01). Median OS for CLIP scores 2–3 was 7 months versus 1.3 months for scores 4–5 (p = 0.04). Conclusions 90Y-microspheres are tolerated in patients with HCC and major PVT. Compared with chemoembolization, rates of severe adverse events appear low. Radiographic response rates are low. Median OS of 7 months is promising and warrants further study versus systemic therapy. PMID:20691606

  11. A comparison of patients with hepatitis B- or hepatitis C-based advanced-stage hepatocellular carcinoma.

    PubMed

    Carr, Brian I; Guerra, Vito; Steel, Jennifer L; Lu, Sheng-Nan

    2015-04-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer death and has characteristic causes, epidemiology and clinical features. The leading causes include hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholism, and aflatoxin B1 dietary exposure, as well as combinations of these factors. Few cancers offer the opportunity to study the clinical and cancer phenotype that results from different causes, quite like HCC. Advantage was taken of a large cohort of advanced, unresectable and untransplantable HCCs to compare the phenotypes resulting from HBV-based compared with HCV-based HCC. The main findings were that HBV-based HCC patients were statistically significantly younger, had a higher percent of males, had larger maximum tumor sizes, and had higher blood alpha-fetoprotein (AFP) and albumin levels and platelet counts than HCV-based HCC patients. These differences partly reflect an earlier age of HBV infection and a lesser degree of cirrhosis-associated liver damage, as a result of the different biological consequences of chronic HBV compared with chronic HCV infection. PMID:25843735

  12. Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    PubMed Central

    Takino, Jun-ichi; Nagamine, Kentaro; Hori, Takamitsu; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC. PMID:26483867

  13. A combination of sorafenib and SC-43 is a synergistic SHP-1 agonist duo to advance hepatocellular carcinoma therapy.

    PubMed

    Chao, Tzu-I; Tai, Wei-Tien; Hung, Man-Hsin; Tsai, Ming-Hsien; Chen, Min-Hsuan; Chang, Mao-Ju; Shiau, Chung-Wai; Chen, Kuen-Feng

    2016-02-28

    Sorafenib is the first and currently the only standard treatment for advanced hepatocellular carcinoma (HCC). We previously developed a sorafenib derivative SC-43, which exhibits much more enhanced anti-HCC activity than sorafenib and also promotes apoptosis in sorafenib-resistant HCC cells. Herein, a novel "sorafenib plus" combination therapy was developed by coupling sorafenib treatment with SC-43. Both sorafenib and SC-43 are proven Src homology region 2 domain containing phosphatase 1 (SHP-1) agonists. The combined actions of sorafenib and SC-43 enhanced SHP-1 activity, which was associated with diminished STAT3-related signals and stronger expression of apoptotic genes above that of either drug alone, culminating in increased cell death. Decreased p-STAT3 signaling and tumor size, as well as increased SHP-1 activity were observed in mice receiving the combination therapy in a subcutaneous HCC model. More reduced orthotopic HCC tumor size and prolonged survival were also observed in mice in the combination treatment arm compared to mice in either of the monotherapy arms. These results in the preclinical setting pave the way for further clinical studies to treat unresectable HCC. PMID:26679051

  14. Effective hepatic artery chemoembolization for advanced hepatocellular carcinoma with multiple tumor thrombi and pulmonary metastases: A case report

    PubMed Central

    Huang, De-Jia; Li, Yan-Hao; Luo, Yao-Chang; Huang, Jun-Zhen; He, Hai-Yuan

    2016-01-01

    Advanced hepatocellular carcinoma (HCC) with tumor thrombi invading the portal vein and extending into the right atrium (RA) through the hepatic vein is regarded as a terminal-stage condition. Intracardiac tumor thrombus and treatment via liver resection has been reported in the current literature, but results from this therapeutic approach remain unsatisfactory. The present study describes a rare case of HCC with metastatic portal vein, middle hepatic vein, inferior vena cava (IVC) and RA tumor thrombi, and pulmonary metastases. A 29-year-old woman was admitted to The First Affiliated Hospital of Guangxi Traditional Chinese Medical University (Nanning, China) subsequent to experiencing right upper quadrant abdominal pain. Following diagnosis, based on computed tomography analysis and laboratory data, the patient underwent an initial transcatheter arterial chemoembolization (TACE) treatment using fluorouracil (5-FU), pirarubicin, mitomycin C, Lipiodol and sodium alginate microball (KMG). At 1 month post-treatment, serum α-fetoprotein levels remained at >1,000 ng/ml. Subsequently, the patient underwent a second TACE treatment. At 1 month after the second treatment, the abdominal pain had been alleviated and the serum α-fetoprotein levels were reduced to <20 ng/ml. Imaging analysis indicated a marked reduction in tumor burden in the liver and the hepatic vein and IVC tumor thrombi. Furthermore, the portal vein and RA tumor thrombi, and the pulmonary metastases had disappeared. At 40 months after the second TACE therapy, the patient remains alive without any signs of recurrence. The present case demonstrates that the administration of TACE, using 5-FU, pirarubicin, mitomycin C, Lipiodol and KMG, functions as an effective treatment in cases of unresectable advanced HCC presenting with pulmonary metastases and extensive tumor thrombi in the IVC, the RA and one branch of the portal vein. PMID:27602147

  15. [A case of advanced hepatocellular carcinoma successfully treated by liver resection after complete response induced by sorafenib administration].

    PubMed

    Kim, Yongkook; Hosoda, Yohei; Kakita, Naruyasu; Yamada, Yukinori; Yamasaki, Masaru; Nishino, Masaya; Okano, Miho; Nagai, Kenichi; Yasui, Masayoshi; Tsujinaka, Toshimasa

    2014-11-01

    A 50-year-old man presented to our hospital with the chief complaint of right hypochondriac pain and a palpable tumor. Advanced hepatocellular carcinoma (HCC) and chronic hepatitis B infection were diagnosed and treated by twice-repeated transcatheterarterial chemoembolization (TACE) followed by administration of entecavir. Two months after the last TACE, alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonistII (PIVKA-II) levels had elevated, and multiple small early enhancing nodules were detected on computed tomography(CT)scan. Based on his age and liver function (Child-Pugh score A5), a full dose of sorafenib (800 mg/day) was administered. The sorafenib dose was decreased after one month to 400mg/day because of hand-foot syndrome. Following sorafenib administration, the lesions shrank markedly, and complete response (CR) according to modified Response Evaluation Criteria In Solid Tumors(mRECIST)was achieved within 4 months. Six months after sorafenib treatment was begun, recurrent HCC was detected in segment 6, near the previously treated lesion. The decreased size of the main tumor and normalization of AFP levels allowed curative surgical resection. The patient was discharged 5 days after surgery and is currently treated with a half dose of sorafenib. Thirteen months after surgery, a small early enhancing lesion is visible on postoperative CT scan, but AFP and PIVKA-II levels are still keeping in a normal range. This case demonstrates that if sorafenib treatment is effective, then subsequent surgical treatment can be reconsidered in patients with advanced HCC responding to this combined therapy. PMID:25731444

  16. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    SciTech Connect

    Chen, Shang-Wen; Lin, Li-Ching; Kuo, Yu-Cheng; Liang, Ji-An; Kuo, Chia-Chun; Chiou, Jeng-Fong

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  17. Irreversible electroporation of locally advanced pancreatic neck/body adenocarcinoma

    PubMed Central

    2015-01-01

    Objective Irreversible electroporation (IRE) of locally advanced pancreatic adenocarcinoma of the neck has been used to palliate appropriate stage 3 pancreatic cancers without evidence of metastasis and who have undergone appropriate induction therapy. Currently there has not been a standardized reported technique for pancreatic mid-body tumors for patient selection and intra-operative technique. Patients Subjects are patients with locally advanced pancreatic adenocarcinoma of the body/neck who have undergone appropriate induction chemotherapy for a reasonable duration. Main outcome measures Technique of open IRE of locally advanced pancreatic adenocarcinoma of the neck/body is described, with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open IRE of the pancreatic neck/body with bracketing of the celiac axis and superior mesenteric artery with continuous intraoperative ultrasound imaging and consideration of intraoperative navigational system is described. Conclusions IRE of locally advanced pancreatic adenocarcinoma of the body/neck is feasible for appropriate patients with locally advanced unresectable pancreatic cancer. PMID:26029461

  18. Frequency of Elevated Hepatocellular Carcinoma (HCC) Biomarkers in Patients with Advanced Hepatitis C

    PubMed Central

    Sterling, Richard K.; Wright, Elizabeth C.; Morgan, Timothy R.; Seeff, Leonard B.; Hoefs, John C.; Di Bisceglie, Adrian M.; Dienstag, Jules L.; Lok, Anna S.

    2013-01-01

    Background Prospective studies of serum HCC biomarkers in patients with advanced hepatitis C are lacking. Aims To determine frequencies and performance of elevated alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin (DCP) levels as HCC biomarkers in advanced hepatitis C. Methods Patients in the HALT-C Trial were tested every 3 months for 42 months. Screening ultrasound was performed every 12 months. Levels of biomarkers were compared in patients in whom HCC did or did not develop. Results 855 patients were evaluated; HCC developed in 46. Among patients without HCC, 73.2% had AFP consistently <20, 24.5% had at least one AFP between 20-199, while 2.3% had at least one AFP value ≥200 ng/mL; 73.7% had DCP consistently <90, 11.6% had at least one DCP between 90-149, and 14.7% had at least one DCP value ≥150 mAU/mL. AFP-L3 ≥10% was present at least once in 9.0% and in 17.1% of those with AFP >20 ng/mL. Among all patients with elevated biomarkers, a diagnosis of HCC was made in 0-31.6% (depending on the biomarker and cutoff) during the subsequent 24 months. AFP ≥200 ng/mL had the highest specificity (99%), but sensitivity was ≤20%. DCP ≥40 mAU/mL had the highest sensitivity (76%), but specificity was ≤58%. Independent predictors of elevated AFP were gender (female), race (Black), more advanced disease, and HCC. Elevated DCP was associated with more advanced disease and HCC. Conclusions Mild-moderate elevations in total AFP and DCP but not AFP-L3 occur frequently in patients with chronic hepatitis C and advanced fibrosis, are related to factors other than HCC, and are poor predictors of HCC. PMID:21931376

  19. Transcatheter Arterial Chemoembolization for Advanced Hepatocellular Carcinoma with Inferior Vena Cava and Right Atrial Tumors

    SciTech Connect

    Chern, M. C. Chuang, V. P. Cheng, T. Lin, Z. H. Lin, Y. M.

    2008-07-15

    Advanced hepatocelluar carcinoma (HCC) with invasion of venous systems usually indicates not only a poor prognosis but also a contraindication for transcatheter arterial chemoembolization (TACE). This study evaluated the feasibility of TACE for advanced HCC with inferior vena cava (IVC) and right atrium (RA) tumors and, also, to search for the ideal embolization particle size. Twenty-six patients who had HCC invasion into the IVC included five patients with coexistent RA tumors that were treated with TACE. The chemoembolization method was cisplatin, doxorubicin, and mitomycin C mixed with Lipiodol and Ivalon. The selection of Ivalon particles was divided into two groups based on their size: (A) >180 {mu}m, N = 9; and (B) 47-180 {mu}m, N = 17. The overall response rate was 53.8% (14/26). Based on the response to TACE, the median survival period of the entire group was 4.2 months (range, 1.5 to 76.7 months). The median survival period of the 14 responders was 13.5 months (1.5-76.7 months), and that of the 12 nonresponders, 3.3 months (2.1 to 24.3 months) (p < 0.002). Comparing the two Ivalon particle sizes, the response rate was 12.5% (1/9 patients) for group A and 76.5% for group B (13/17 patients) (p < 0.02). No serious complication was observed post-chemoembolization. In conclusion, TACE is a safe and effective treatment for advanced HCC with IVC and RA tumors, and small Ivalon particles (47-180 {mu}m) are superior to large ones (>180 {mu}m).

  20. The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

    PubMed Central

    Dong, Shengli; Tang, Qibin; Long, Miaoyun; Guan, Jian; Ye, Lu; Li, Gaopeng

    2013-01-01

    Background/aim A local nanotherapy (LNT) combining the therapeutic efficacy of trans-arterial embolization, nanoparticles, and p53 gene therapy has been previously presented. The study presented here aimed to further improve the incomplete tumor eradication and limited survival enhancement and to elucidate the molecular mechanism of the LNT. Methods In a tumor-targeting manner, recombinant expressing plasmids harboring wild-type p53 and Rb were either co-transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol® (Guerbet, Villepinte, France) emulsion via the hepatic artery. Subsequent co-expression of p53 and Rb proteins within the treated tumors was investigated by Western blotting and in situ analysis by laser-scanning confocal microscopy. The therapeutic effect was evaluated by the tumor growth velocity, apoptosis and necrosis rates, their sensitivity to Adriamycin® (ADM), mitomycin C, and fluorouracil, the microvessel density of tumor tissue, and the survival time of animals. Eventually, real-time polymerase chain reaction and enhanced chemiluminescence Western blotting were used to investigate the expressive changes of important genes related to the therapy. Results The administration procedure proved safe for the rabbits’ liver function, the p53 plus Rb LNT showed significantly better antitumoral effect and lower expression of malignant genes than the p53 or Rb LNT, although no significant difference was observed in animal survival when the p53 plus Rb LNT was compared with the p53 LNT. Conclusion Rb works synergistically with p53 in combined therapy mediated by a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex to augment the antitumoral effect through the downregulated expression of important genes related to apoptosis, necrosis, growth, differentiation and multidrug resistance of tumor cells. LNT with p53 and Rb is potentially an effective antitumor

  1. Epithelial-mesenchymal transition-related genes are linked to aggressive local recurrence of hepatocellular carcinoma after radiofrequency ablation.

    PubMed

    Iwahashi, Shuichi; Shimada, Mitsuo; Utsunomiya, Tohru; Imura, Satoru; Morine, Yuji; Ikemoto, Tetsuya; Takasu, Chie; Saito, Yu; Yamada, Shinichiro

    2016-05-28

    We reported that poor prognoses of hepatocellular carcinoma (HCC) patients after radiofrequency ablation (RFA) are owing to up-regulation of expression of hypoxia-inducible factor-1 and epithelial cell adhesion molecule. We investigated aggressive progression in residual liver tumors (RLTs) after RFA to focus on expression of epithelial-mesenchymal transition (EMT)-related genes and miRNAs. Ten patients with recurrent HCC post-RFA who underwent hepatectomy (RFA group) and 78 patients with HCC without prior RFA (non-RFA group) were enrolled. We examined expression of transforming growth factor (TGF)-β, Twist, vimentin, and Snail-1 mRNAs in tumor tissues, and expression of miR-34a and miR-200c. Expression of TGF-β, Twist and Snail-1 in the RFA group was significantly higher than that in the non-RFA group (P < 0.05); vimentin expression in the RFA group was higher than that in the non-RFA group (P = 0.07). Expression of miR-200c and miR-34a in the RFA group was significantly lower than that in the non-RFA group (miR-200c: P = 0.04; miR-34a: P < 0.01). Increased expression of EMT markers through down-regulation of miRNA expression in RLTs after RFA may be related to poor prognoses of HCC patients with aggressive local recurrence after RFA. PMID:26940140

  2. Does Establishing a Safety Margin Reduce Local Recurrence in Subsegmental Transarterial Chemoembolization for Small Nodular Hepatocellular Carcinomas?

    PubMed Central

    Kang, Hyo-Jin; Kim, Young Il; Kim, Hyo-Cheol; Jae, Hwan Jun; Hur, Saebeom

    2015-01-01

    Objective To test the hypothesis that a safety margin may affect local tumor recurrence (LTR) in subsegmental chemoembolization. Materials and Methods In 101 patients with 128 hepatocellular carcinoma (HCC) nodules (1-3 cm in size and ≤ 3 in number), cone-beam CT-assisted subsegmental lipiodol chemoembolization was performed. Immediately thereafter, a non-contrast thin-section CT image was obtained to evaluate the presence or absence of intra-tumoral lipiodol uptake defect and safety margin. The effect of lipiodol uptake defect and safety margin on LTR was evaluated. Univariate and multivariate analyses were performed to indentify determinant factors of LTR. Results Of the 128 HCC nodules in 101 patients, 49 (38.3%) nodules in 40 patients showed LTR during follow-up period (median, 34.1 months). Cumulative 1- and 2-year LTR rates of nodules with lipiodol uptake defect (n = 27) and those without defect (n = 101) were 58.1% vs. 10.1% and 72.1% vs. 19.5%, respectively (p < 0.001). Among the 101 nodules without a defect, the 1- and 2-year cumulative LTR rates for nodules with complete safety margin (n = 52) and those with incomplete safety margin (n = 49) were 9.8% vs. 12.8% and 18.9% vs. 19.0% (p = 0.912). In multivariate analyses, ascites (p = 0.035), indistinct tumor margin on cone-beam CT (p = 0.039), heterogeneous lipiodol uptake (p = 0.023), and intra-tumoral lipiodol uptake defect (p < 0.001) were determinant factors of higher LTR. Conclusion In lipiodol chemoembolization, the safety margin in completely lipiodolized nodule without defect will not affect LTR in small nodular HCCs. PMID:26357501

  3. Stereotactic Body Radiation Therapy Boost in Locally Advanced Pancreatic Cancer

    SciTech Connect

    Seo, Young Seok; Kim, Mi-Sook; Yoo, Sung Yul; Cho, Chul Koo; Yang, Kwang Mo; Yoo, Hyung Jun; Choi, Chul Won; Lee, Dong Han; Kim, Jin; Kim, Min Suk; Kang, Hye Jin; Kim, YoungHan

    2009-12-01

    Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity. Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated. Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival. Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

  4. The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    2016-01-01

    Background Whether radiologically detected progressive disease (PD) is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC) is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC. Methods We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥3; 86 patients were ultimately enrolled. Results Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group), whereas 39 did not (the discontinuous group). The median survival time (MST) in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01). The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01); it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03). In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01). Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval): ECOG PS <2 (0.290, 0.107–0.880), Barcelona Clinical Liver Cancer stage B (0.146, 0.047–0.457), serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355–5.691), and post-PD sorafenib administration (0.279, 0.150–0.510). Conclusion Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients. PMID:26745625

  5. Development and microwave analysis of slot antennas for localized hyperthermia treatment of hepatocellular liver tumor.

    PubMed

    Zafar, T; Zafar, J; Zafar, H

    2014-12-01

    Slot antennas are often considered as a suitable choice for microwave ablation due to design simplicity, low cost to manufacture and a highly confined temperature profile. In this paper, an iterative coupled thermal/microwave numerical formulation is presented to analyze and develop miniature slot antenna geometries for localized liver cancer treatment. The thermal solver determines the specific absorption rate (SAR) as a pre-processing step to determine the temperature distribution profile within malignant tissues. The microwave solver uses this computed thermal solution together with related boundary/sub-domain settings to determine complex propagation wave number as an Eigen value. The desired microwave response in terms of insertion loss <0.1 dB, VSWR 1:1.1, and return loss less than -22 dB was achieved at 2.45 GHz. The simulated results agree well with the measured response. PMID:25370955

  6. Syed-Neblett interstitial template in locally advanced gynecological malignancies

    SciTech Connect

    Ampuero, F.; Doss, L.L.; Khan, M.; Skipper, B.; Hilgers, R.D.

    1983-12-01

    Twenty-eight patients with locally advanced malignancies of the cervix and vagina were treated with a combination of external radiation therapy and after loading Syed-Neblett iridium template. There were 22 patients with squamous cell cancer and two patients with adenocarcinomas of the cervix. Four patients with squamous cell cancer of the vagina were treated with this method. Only patients with locally advanced disease (cervical lesion >4 cm in diameter) and poor vagnal anatomy were selected for this modality of therapy. In this series the incidence of distant failures of 39% seems to confirm the significance of local volume of disease as a prognostic indicator; despite a local control rate of 59%, only 33% of the patients are alive from 25-51 months. Complications occurred in 12 patients (42%). Six patients (22%) developed severe rectal stricture or rectovaginal fistula necessitating diverting sigmoid colostomy; five patients (18%) developed hemorrhagic proctitis with diarrhea and tenesmus; one patient developed vaginal vault necrosis. Complications occurred 7 to 24 months following therapy. Six of the 12 patients developing complications are dead of disease. On the basis of this study and because of the low cure rate and high incidence of complications, the value of the Syed-Neblett template in locally advanced gynecologic malignancies should be reconsidered.

  7. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer.

    PubMed

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40-60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  8. Localization of gravitational wave sources with networks of advanced detectors

    SciTech Connect

    Klimenko, S.; Mitselmakher, G.; Pankow, C.; Vedovato, G.; Drago, M.; Prodi, G.; Mazzolo, G.; Salemi, F.; Re, V.; Yakushin, I.

    2011-05-15

    Coincident observations with gravitational wave (GW) detectors and other astronomical instruments are among the main objectives of the experiments with the network of LIGO, Virgo, and GEO detectors. They will become a necessary part of the future GW astronomy as the next generation of advanced detectors comes online. The success of such joint observations directly depends on the source localization capabilities of the GW detectors. In this paper we present studies of the sky localization of transient GW sources with the future advanced detector networks and describe their fundamental properties. By reconstructing sky coordinates of ad hoc signals injected into simulated detector noise, we study the accuracy of the source localization and its dependence on the strength of injected signals, waveforms, and network configurations.

  9. Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

    PubMed Central

    Conde-Muíño, Raquel; Cuadros, Marta; Zambudio, Natalia; Segura-Jiménez, Inmaculada; Cano, Carlos; Palma, Pablo

    2015-01-01

    There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile's ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice. PMID:26504848

  10. Combined approach to hepatocellular carcinoma: a new treatment concept for nonresectable disease.

    PubMed

    Strebel, Bruno M; Dufour, Jean-François

    2008-11-01

    Depending on tumor burden, hepatic function and patients' performance status, hepatocellular carcinoma is treated by surgery, local procedures, systemic therapy or palliation. The majority of patients are diagnosed at a stage where local therapy is the treatment of choice. Recently, the multikinase inhibitor sorafenib was found to improve the survival of patients with advanced hepatocellular carcinoma and conserved liver function. In this manuscript, we summarize the experimental evidence supporting the combination of a systemic targeted therapy with a local therapy. We also discuss the pros and cons of different schedules of combining such treatments. We conclude that there is enough of a theoretical argument to design clinical trials testing this strategy. PMID:18983234

  11. Early Clinical Response after 2 Weeks of Sorafenib Therapy Predicts Outcomes and Anti-Tumor Response in Patients with Advanced Hepatocellular Carcinoma

    PubMed Central

    Kuzuya, Teiji; Ishigami, Masatoshi; Ishizu, Yoji; Honda, Takashi; Hayashi, Kazuhiko; Katano, Yoshiaki; Hirooka, Yoshiki; Ishikawa, Tetsuya; Nakano, Isao; Goto, Hidemi

    2015-01-01

    Background & Aims We evaluated the relationship between the early clinical response after 2 weeks of sorafenib therapy and the outcomes and anti-tumor response in patients with advanced hepatocellular carcinoma. Methods Fifty-seven patients who had intrahepatic hypervascular hepatocellular carcinoma and Child-Pugh (CP) class A disease at baseline were enrolled in this prospective, multicenter, observational, non-interventional study. As an early clinical response after 2 weeks of sorafenib therapy, changes in intra-tumor blood flow on contrast-enhanced computed tomography (CE-CT), alpha-fetoprotein (AFP) levels, and remnant liver function were investigated. Results After 2 weeks of sorafenib therapy, there were 26 patients (45.6%) without disappearance of arterial tumor enhancement on CE-CT, 15 patients (26.3%) with an AFP ratio of >1.2, and seven patients (12.3%) with two or more increments in the CP score. Multivariate analysis showed that the absence of disappearance of arterial tumor enhancement on CE-CT, AFP ratio of >1.2, and two or more increments in the CP score after 2 weeks of sorafenib therapy were significant and independent predictors of worse survival. Upon scoring these three variables as "poor prognostic factors", patients with poor prognostic score 4, 3 or 2 (n = 17) had significantly worse outcomes and a significantly higher progressive disease (PD) rate based on modified Response Evaluation Criteria in Solid Tumors at 6 weeks after sorafenib therapy than those with poor prognostic score 1 or 0 (n = 40) (median overall survival: 194 days vs. 378 days; p = 0.0010, PD rate: 70.6% vs. 20.0%; p = 0.0003, respectively). Conclusions Changes in intra-tumor blood flow on CE-CT, AFP levels, and remnant liver function after 2 weeks of sorafenib therapy may be useful for predicting the outcomes and anti-tumor response to sorafenib in patients with advanced hepatocellular carcinoma. PMID:26421430

  12. Trametinib or Combination Chemotherapy in Treating Patients With Refractory or Advanced Biliary or Gallbladder Cancer or That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-07-29

    Adult Cholangiocarcinoma; Advanced Adult Hepatocellular Carcinoma; BCLC Stage C Adult Hepatocellular Carcinoma; BCLC Stage D Adult Hepatocellular Carcinoma; Hilar Cholangiocarcinoma; Localized Non-Resectable Adult Liver Carcinoma; Recurrent Adult Liver Carcinoma; Recurrent Childhood Liver Cancer; Recurrent Extrahepatic Bile Duct Carcinoma; Recurrent Gallbladder Carcinoma; Stage II Gallbladder Cancer; Stage III Childhood Hepatocellular Carcinoma; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Childhood Hepatocellular Carcinoma; Stage IV Distal Bile Duct Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer; Unresectable Extrahepatic Bile Duct Carcinoma

  13. Locally advanced pancreatic cancer. Looking beyond traditional chemotherapy and radiation.

    PubMed

    Savir, Guy; Huber, Kathryn E; Saif, Muhammad Wasif

    2013-07-01

    About a third of all pancreatic cancer is found to be locally advanced at the time of diagnosis, where the tumor is inoperable but remains localized to the pancreas and regional lymphatics. Sadly, this remains a universally deadly disease with progression to distant disease being the predominant mode of failure and average survival under one year. Optimal treatment of these patients continues to be an area of controversy, with chemotherapy alone being the treatment preference in Europe, and chemotherapy followed by chemoradiation in selected patients, preferred in the USA. The aim of this paper is to summarize the key abstracts presented at the 2013 ASCO Annual Meeting that address evolving approaches to the management of locally advanced pancreatic cancer. The late breaking abstract (#LBA4003) provided additional European data showing non-superiority of chemoradiation compared to chemotherapy in locally advanced pancreatic cancer patients without distant progression following 4 months of chemotherapy. Another late breaking abstract, (#LBA4004), unfortunately showed a promising new complement to gemcitabine and capecitabine using immunotherapy in the form of a T-helper vaccine did not translate to improved survival in the phase III setting. PMID:23846922

  14. The Importance of Lamivudine Therapy in Liver Cirrhosis Patients Related HBV with Advanced Hepatocellular Carcinoma Receiving Hepatic Arterial Infusion Chemotherapy

    PubMed Central

    Momiyama, Koichi; Nagai, Hidenari; Ogino, Yu; Mukouzu, Takanori; Matsui, Daigo; Kogame, Michio; Matsui, Teppei; Wakui, Noritaka; Shinohara, Mie; Igarashi, Yoshinori; Sumino, Yasukiyo

    2015-01-01

    Purpose: We have previously reported that continuous hepatic arterial infusion chemotherapy (HAIC) might be more effective for advanced hepatocellular carcinoma (aHCC) in patients with liver cirrhosis (LC) related to HCV infection (C-LC) or alcohol abuse (A-LC) than in patients who had LC related to HBV infection (B-LC). The aim of the present study was to retrospectively assess the efficacy of lamivudine therapy for B-LC patients with aHCC undergoing HAIC. Methods: Seventeen adult Japanese B-LC patients with aHCC were treated by HAIC with or without lamivudine (100 mg/day) between 2002 and 2008 at our hospital. Their tumors were inoperable according to computed tomography findings. HAIC (LV at 12 mg/hr, CDDP at 10 mg/hr, and 5-FU at 250 mg/22 hr) was given via the proper hepatic artery every 5 days for 4 weeks using a catheter connected to a subcutaneously implanted drug delivery system. Results: Nine of the 17 patients received lamivudine at a dose of 100 mg/day together with HAIC (LAM group), while 8 patients did not receive lamivudine and only had HAIC (non-LAM group). The response rate was 12.5 in the non-LAM group and 0.0% in the LAM group. However, the survival of the LAM group was better than that of the non-LAM group, although there was no significant difference between them. The median survival time of the LAM and non-LAM groups was 310 and 157 days, respectively. HBV-DNA levels were significantly lower after chemotherapy compared with that before chemotherapy in the LAM group. In the non-LAM group, the percentage of Th2 cells before HAIC and after HAIC was significantly higher than in the control group. However, the percentage of Th2 cells in the LAM group after HAIC was not different from that in the control group, although it was significantly higher in the LAM group than in the control group before chemotherapy. Conclusions: These results indicate that lamivudine therapy may prolong the survival of B-LC patients receiving HAIC for aHCC by reducing HBV

  15. Safety and efficacy of sorafenib in patients with advanced hepatocellular carcinoma and Child-Pugh A or B cirrhosis

    PubMed Central

    FEDERICO, ALESSANDRO; ORDITURA, MICHELE; COTTICELLI, GAETANO; DE SIO, ILARIO; ROMANO, MARCO; GRAVINA, ANTONIETTA GERARDA; DALLIO, MARCELLO; FABOZZI, ALESSIO; CIARDIELLO, FORTUNATO; LOGUERCIO, CARMELA; DE VITA, FERDINANDO

    2015-01-01

    Sorafenib confers a survival benefit for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) A liver cirrhosis. At present, limited data exists with regard to the safety and efficacy of sorafenib in treating CP-B HCC patients. The present study describes the use of sorafenib in patients with HCC and CP-A or -B cirrhosis. Clinical data was obtained from patients with HCC who were treated with sorafenib at the Department of Clinical and Experimental Medicine, Second University of Naples (Naples, Italy) and were analyzed retrospectively in terms of tumor response, tolerance and survival. The treatment outcomes were analyzed according to the respective CP status. The adverse events (AEs) were graded using the Common Terminology Criteria for Adverse Events, version 3.0, and the tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.2. In total, 26 patients received sorafenib at 400 mg twice daily. The median age was 69 years (range, 58–81 years) and the ratio of males to females was 18:8. Overall, 15 patients were infected with the hepatitis C virus (HCV), eight with HBV and three were co-infected with HCV/HBV. In total, 20 (77%) patients presented with an underlying CP-A (CP-A5 and CP-A6) cirrhosis and six (23%) with CP-B (CP-B7). Previous treatments included surgery (n=4), transarterial chemoembolization (n=5) and percutaneous ethanol injection or radiofrequency interstitial thermal ablation (n=12). A partial response was observed in three patients (12%), a stable disease lasting at least 12 weeks in 13 patients (50%) and a progression of disease in 10 patients (38%). The median overall survival (OS) time was 7.4 months [95% confidence interval (CI), 3.2–11.6) and the median progression-free survival (PFS) time was 3.7 months (95% CI, 1.9–5.5). The median OS and PFS times differed between patients with CP-A and CP-B, with a trend (P=0.06) toward a worse outcome in those with CP-B, although this

  16. Selective Mastectomy in the Management of Locally Advanced Breast Cancer

    SciTech Connect

    Ahern, Verity . E-mail: verity.ahern@swahs.healthnsw.gov.au; Boyages, John; Gebski, Val M. Stat; Moon, Dominic; Wilcken, Nicholas

    2007-07-15

    Purpose: To evaluate local control for patients with locally advanced noninflammatory breast cancer (LABC) managed by selective mastectomy. Methods and Materials: Between 1979 and 1996, 176 patients with LABC were prospectively managed by chemotherapy (CT)-irradiation (RT)-CT without routine mastectomy. All surviving patients were followed for a minimum of 5 years. Results: A total of 132 patients (75%) had a T4 tumor and 22 (12.5%) supraclavicular nodal disease. The clinical complete response rate was 91% (160/176), which included 13 patients who underwent mastectomy and 2 an iridium wire implant. The first site of failure was local for 43 patients (breast {+-} axilla for 38); 27 of these patients underwent salvage mastectomy and 11 did not for an overall mastectomy rate of 23% (40/176). If all 176 patients had undergone routine mastectomy (136 extra mastectomies), 11 additional patients may have avoided an unsalvageable first local relapse. The others would have either have not had a local relapse or would have suffered local relapse after distant disease. No tumor or treatment related factor was found to predict local disease at death. Median disease-free and overall survival for all patients was 26 and 52 months, respectively. Conclusions: Selective mastectomy in LABC may not jeopardize local control or survival.

  17. Locally Advanced Gastroesophageal Junction Tumor: A Treatment Dilemma

    PubMed Central

    Ashraf, Noman; Hoffe, Sarah

    2015-01-01

    Over the last several decades, the incidence of adenocarcinoma of the gastroesophageal junction (GEJ) has been increasing in developed countries. Although complete surgical resection remains the cornerstone of treatment for resectable disease, long-term outcomes are poor and recurrence rates are high with surgery alone in patients presenting with locally advanced disease. Multimodal therapy has been shown to improve survival; however, the optimal therapeutic approach remains controversial, and practices vary across the world. Preoperative chemoradiotherapy is generally used in the U.S., whereas perioperative chemotherapy without radiation is favored in most European countries. In this review, we discuss why the treatment of locally advanced GEJ tumors remains controversial, examine the evidence for various multimodal approaches, discuss their respective pros and cons, evaluate the role of radiation therapy, highlight some ongoing and planned clinical trials, and suggest areas that need further research. PMID:25561508

  18. Locally advanced gastroesophageal junction tumor: a treatment dilemma.

    PubMed

    Ashraf, Noman; Hoffe, Sarah; Kim, Richard

    2015-02-01

    Over the last several decades, the incidence of adenocarcinoma of the gastroesophageal junction (GEJ) has been increasing in developed countries. Although complete surgical resection remains the cornerstone of treatment for resectable disease, long-term outcomes are poor and recurrence rates are high with surgery alone in patients presenting with locally advanced disease. Multimodal therapy has been shown to improve survival; however, the optimal therapeutic approach remains controversial, and practices vary across the world. Preoperative chemoradiotherapy is generally used in the U.S., whereas perioperative chemotherapy without radiation is favored in most European countries. In this review, we discuss why the treatment of locally advanced GEJ tumors remains controversial, examine the evidence for various multimodal approaches, discuss their respective pros and cons, evaluate the role of radiation therapy, highlight some ongoing and planned clinical trials, and suggest areas that need further research. PMID:25561508

  19. Deinterlacing algorithm with an advanced non-local means filter

    NASA Astrophysics Data System (ADS)

    Wang, Jin; Jeon, Gwanggil; Jeong, Jechang

    2012-04-01

    The authors introduce an efficient intra-field deinterlacing algorithm using an advanced non-local means filter. The non-local means (NLM) method has received considerable attention due to its high performance and simplicity. The NLM method adaptively obtains the missing pixel by the weighted average of the gray values of all pixels within the image, and then automatically eliminates unrelated neighborhoods from the weighted average. However, spatial location distance is another important issue for the deinterlacing method. Therefore we introduce an advanced NLM (ANLM) filter while consider neighborhood similarity and patch distance. Moreover, the search region of the conventional NLM is the whole image, while, the ANLM can just utilize the limited search region and achieve good performance and high efficiency. When compared with existing deinterlacing algorithms, the proposed algorithm improves the peak signal-to-noise-ratio while maintaining high efficiency.

  20. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  1. P37: Locally advanced thymoma-robotic approach

    PubMed Central

    Asaf, Belal B.; Kumar, Arvind

    2015-01-01

    Background The conventional approach to locally advanced thymoma has been via a sternotomy. VATS and robotic thymectomies have been described but typically are reserved for patients with myasthenia gravis only or for small, encapsulated thymic tumors. There have been few reports of minimally invasive resection of locally advanced thymomas. Our objective is to present a case in which a large, locally advanced thymoma was resected en bloc with the pericardium employing robotic assisted thoracoscopic approach. Methods This case illustrates a case of an asymptomatic 29-year-old female found to have an 11 cm anterior mediastinal mass on CT scan. A right-sided, 4 port robotic approach was utilized with the camera port in the 5th intercostal space anterior axillary line and two accessory ports for robotic arm 1 and 2 in the 3rd intercostal space anterior axillary line and 8th intercostal space anterior axillary line. A 5 mm port was used between the camera and 2nd robotic arm for assistance. On exploration the mass was found to be adherent to the pericardium that was resected en bloc via anterior pericardiectomy. Her post-operative course was uncomplicated, and she was discharged home on postoperative day 1. Results Final pathology revealed an 11 cm × 7.5 cm × 3.0 cm WHO class B2 thymoma invading the pericardium, TNM stage T3N0M0, with negative margins. The patient was subsequently sent to receive 5,040 cGy of adjuvant radiation, and follow-up CT scan 6 months postoperatively showed no evidence of disease. Conclusions Very little data exist demonstrating the efficacy of resecting locally advanced thymomas utilising the minimally invasive approach. Our case demonstrates that a robotic assisted thoracoscopic approach is feasible for performing thymectomy for locally advanced thymomas. This may help limit the morbidity of a trans-sternal approach while achieving comparable oncologic results. However, further studies are needed to evaluate its efficacy and long term

  2. Radiological Features of Hepatocellular Carcinoma

    PubMed Central

    Shah, Samir; Shukla, Akash; Paunipagar, Bhawan

    2014-01-01

    Present article is a review of radiological features of hepatocellular carcinoma on various imaging modalities. With the advancement in imaging techniques, biopsy is rarely needed for diagnosis of hepatocellular carcinoma (HCC), unlike other malignancies. Imaging is useful not only for diagnosis but also for surveillance, therapy and assessing response to treatment. The classical and the atypical radiological features of HCC have been described. PMID:25755613

  3. Advances in local ablation of malignant liver lesions

    PubMed Central

    Eisele, Robert M

    2016-01-01

    Local ablation of liver tumors matured during the recent years and is now proven to be an effective tool in the treatment of malignant liver lesions. Advances focus on the improvement of local tumor control by technical innovations, individual selection of imaging modalities, more accurate needle placement and the free choice of access to the liver. Considering data found in the current literature for conventional local ablative treatment strategies, virtually no single technology is able to demonstrate an unequivocal superiority. Hints at better performance of microwave compared to radiofrequency ablation regarding local tumor control, duration of the procedure and potentially achievable larger size of ablation areas favour the comparably more recent treatment modality; image fusion enables more patients to undergo ultrasound guided local ablation; magnetic resonance guidance may improve primary success rates in selected patients; navigation and robotics accelerate the needle placement and reduces deviation of needle positions; laparoscopic thermoablation results in larger ablation areas and therefore hypothetically better local tumor control under acceptable complication rates, but seems to be limited to patients with no, mild or moderate adhesions following earlier surgical procedures. Apart from that, most techniques appear technically feasible, albeit demanding. Which technology will in the long run become accepted, is subject to future work. PMID:27099433

  4. Advances in local ablation of malignant liver lesions.

    PubMed

    Eisele, Robert M

    2016-04-21

    Local ablation of liver tumors matured during the recent years and is now proven to be an effective tool in the treatment of malignant liver lesions. Advances focus on the improvement of local tumor control by technical innovations, individual selection of imaging modalities, more accurate needle placement and the free choice of access to the liver. Considering data found in the current literature for conventional local ablative treatment strategies, virtually no single technology is able to demonstrate an unequivocal superiority. Hints at better performance of microwave compared to radiofrequency ablation regarding local tumor control, duration of the procedure and potentially achievable larger size of ablation areas favour the comparably more recent treatment modality; image fusion enables more patients to undergo ultrasound guided local ablation; magnetic resonance guidance may improve primary success rates in selected patients; navigation and robotics accelerate the needle placement and reduces deviation of needle positions; laparoscopic thermoablation results in larger ablation areas and therefore hypothetically better local tumor control under acceptable complication rates, but seems to be limited to patients with no, mild or moderate adhesions following earlier surgical procedures. Apart from that, most techniques appear technically feasible, albeit demanding. Which technology will in the long run become accepted, is subject to future work. PMID:27099433

  5. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Mahadevan, Anand; Jain, Sanjay; Goldstein, Michael; Miksad, Rebecca; Pleskow, Douglas; Sawhney, Mandeep; Brennan, Darren M.D.; Callery, Mark; Vollmer, Charles

    2010-11-01

    Purpose: Patients with nonmetastatic locally advanced unresectable pancreatic cancer have a dismal prognosis. Conventional concurrent chemoradiotherapy requires 6 weeks of daily treatment and can be arduous. We explored the safety and effectiveness of a 3-day course of hypofractionated stereotactic body radiotherapy (SBRT) followed by gemcitabine in this population. Patients and Methods: A total of 36 patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with {>=}12 months of follow-up were included. They received three fractions of 8, 10, or 12 Gy (total dose, 24-36 Gy) of SBRT according to the tumor location in relation to the stomach and duodenum, using fiducial-based respiratory motion tracking on a robotic radiosurgery system. The patients were then offered gemcitabine for 6 months or until tolerance or disease progression. Results: With an overall median follow-up of 24 months (range, 12-33), the local control rate was 78%, the median overall survival time was 14.3 months, the median carbohydrate antigen 19-9-determined progression-free survival time was 7.9 months, and the median computed tomography-determined progression-free survival time was 9.6 months. Of the 36 patients, 28 (78%) eventually developed distant metastases. Six patients (17%) were free of progression at the last follow-up visit (range, 13-30 months) as determined by normalized tumor markers with stable computed tomography findings. Nine Grade 2 (25%) and five Grade 3 (14%) toxicities attributable to SBRT occurred. Conclusion: Hypofractionated SBRT can be delivered quickly and effectively in patients with nonmetastatic, locally advanced, unresectable pancreatic cancer with acceptable side effects and minimal interference with gemcitabine chemotherapy.

  6. Preoperative treatment with radiochemotherapy for locally advanced gastroesophageal junction cancer and unresectable locally advanced gastric cancer

    PubMed Central

    Ratosa, Ivica; Oblak, Irena; Anderluh, Franc; Velenik, Vaneja; But-Hadzic, Jasna; Ermenc, Ajra Secerov; Jeromen, Ana

    2015-01-01

    Background. To purpose of the study was to analyze the results of preoperative radiochemotherapy in patients with unresectable gastric or locoregionally advanced gastroesophageal junction (GEJ) cancer treated at a single institution. Patients and methods. Between 1/2004 and 6/2012, 90 patients with locoregionally advanced GEJ or unresectable gastric cancer were treated with preoperative radiochemotherapy at the Institute of Oncology Ljubljana. Planned treatment schedule consisted of induction chemotherapy with 5-fluorouracil and cisplatin, followed by concomitant radiochemotherapy four weeks later. Three-dimensional conformal external beam radiotherapy was delivered by dual energy (6 and 15 MV) linear accelerator in 25 daily fractions of 1.8 Gy in 5 weeks with two additional cycles of chemotherapy repeated every 28 days. Surgery was performed 4–6 weeks after completing radiochemotherapy. Following the surgery, multidisciplinary advisory team reassessed patients for the need of adjuvant chemotherapy. The primary endpoints were histopathological R0 resection rate and pathological response rate. The secondary endpoints were toxicity of preoperative radiochemotherapy and survival. Results. Treatment with preoperative radiochemotherapy was completed according to the protocol in 84 of 90 patients (93.3%). Twenty patients (22.2%) did not undergo the surgery because of the disease progression, serious comorbidity, poor performance status or still unresectable tumour. In 13 patients (14.4%) only exploration was performed because the tumour was assessed as unresectable or diffuse peritoneal carcinomatosis was established. Fifty-seven patients (63.4%) underwent surgery with the aim of complete removal of the tumour. Radical resection was achieved in 50 (55.6%) patients and the remaining seven (7.8%) patients underwent non-radical surgery (R1 in five and R2 in two patients). In this group of patients (n = 57), pathological complete response of tumour was achieved in five

  7. [Concurrent proton therapy and chemotherapy for locally advanced cancers].

    PubMed

    Ishikawa, Hitoshi; Fukumitsu, Nobuyoshi; Ohnishi, Kayoko; Mizumoto, Masashi; Murofushi, Keiko; Numajiri, Haruko; Aihara, Teruhito; Okumura, Toshiyuki; Sakurai, Hideyuki

    2015-02-01

    Charged particles such as protons and carbon-ions offer advantageous physical properties to radiation therapy (RT) for the treatment of various cancers when compared with photons, because they exhibit a spread-out Bragg peak, and may be utilized to achieve a desirable dose distribution to the target volume by using specified beam modulation. Interestingly, the cytocidal effect of protons is almost equal to that of photons, because both protons and photons are considered low-linear energy transfer radiations. Hence, proton beam therapy (PBT) is an attractive RT option, especially in the treatment of locally advanced cancers, as irradiation doses can be safely escalated while sparing the surrounding normal tissues, and because PBT may be concurrently combined with chemotherapy for treating such cancers. Recent advances in PBT techniques including a spot scanning method, as well as an increase in the number of particle therapy institutes are anticipated to yield favorable results through future multi-institutional prospective studies. The University of Tsukuba has carried out several studies to validate the effectiveness of PBT for many types of cancers since 1983. Here, we present our findings on the clinical outcomes of PBT for esophageal cancer, non-small cell lung cancer, intrahepatic biliary tract cancer, pancreas cancer, and bladder cancer; future aspects of PBT concurrently combined with chemotherapy for treating locally advanced cancers are also discussed. PMID:25743133

  8. Hepatocellular carcinoma: A comprehensive review

    PubMed Central

    Waller, Lisa P; Deshpande, Vrushak; Pyrsopoulos, Nikolaos

    2015-01-01

    Hepatocellular carcinoma (HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals with chronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival. PMID:26609342

  9. [A Case of Locally Advanced Gastric Cancer after Neoadjuvant Chemotherapy].

    PubMed

    Okamoto, Tatsuya; Tanaka, Keita; Yonemitsu, Kimihiro; Munechika, Taro; Nomi, Masako; Maeno, Hiroshi; Nagao, Shuji; Kawamoto, Shunji; Sasaguri, Takakazu; Sueishi, Katsuo

    2015-11-01

    A 60s male was admitted to our hospital because of appetite loss and nausea. After examination, he was diagnosed with type 3 advanced gastric cancer in the antrum. Abdominal computed tomography showed gastric cancer invasion to the left liver lobe. We initiated neoadjuvant chemotherapy using S-1 plus CDDP after laparoscopic gastrojejunostomy. S-1 was orally administered for 3 weeks followed by a 2-week drug-free period. CDDP was administered intravenously on day 8 of each course. After 5 courses of chemotherapy, the gastric cancer was reduced in size. We therefore performed total gastrectomy with D2-affiliated left liver resection. S-1 plus CDDP is expected to improve outcomes in unresectable or locally advanced gastric cancer. PMID:26805257

  10. Outcome of nonsurgical treatment for locally advanced thymic tumors

    PubMed Central

    Wang, Chang-Lu; Gao, Lan-Ting; Lv, Chang-Xing; Zhu, Lei

    2016-01-01

    Background Surgical resection remains the mainstay of treatment for patients with early-staged thymic tumors, while chemotherapy is most commonly used in stage IV cases. As for locally advanced thymic tumors, especially those unsuitable for surgery, the optimal therapy is still controversial. Thus, we conducted this retrospective study by comparing three nonsurgical treatment modalities to find some clues. Methods Three treatment modalities were used in 42 patients from October 2000 to December 2010, including radiotherapy (RT) alone, sequential chemoradiation (SCRT) and concurrent chemoradiation (CCRT). Objective response rate (ORR), overall survival (OS) and toxicity of the three regimens were compared accordingly. Results The ORR in all 42 patients was 61.9%, and 5-year OS was 46%. The ORR of RT, SCRT and CCRT were 43.8%, 50% and 87.5%, respectively (RT vs. SCRT, P=0.692; RT vs. CCRT, P=0.009; SCRT vs. CCRT, P=0.051). The 5-year OS of RT, SCRT and CCRT were 30%, 50% and 61.9%, respectively. (RT vs. SCRT, P=0.230; RT vs. CCRT, P=0.011; SCRT vs. CCRT, P=0.282). Eleven patients developed neutropenia of grade 3–4, with 7 in CCRT group and 4 in SCRT, respectively. Nine patients experienced esophagitis of grade 3 with 2 in RT, 3 in SCRT and 4 in CCRT. There were also two cases of grade 3 radiation induced pneumonitis in CCRT group. No life-threatening side effects were noted. Conclusions When used to treat locally advanced thymic tumors unsuitable for surgery, CCRT performed more favorably than RT alone or SCRT in both tumor response and long time survival, but probably with the increasing risk of pulmonary damage. CCRT may offer the best chance of disease control in the management of locally advanced disease. PMID:27114838

  11. Bilateral Blindness Following Chemoradiation for Locally Advanced Oropharyngeal Carcinoma

    PubMed Central

    Zeng, K. Liang; Kuruvilla, Sara; Sanatani, Michael

    2015-01-01

    Wernicke's encephalopathy is a life-threatening neurologic complication of thiamine deficiency. Though the presentation of symptoms can vary widely, the classical triad is founded on ophthalmoplegia, alteration of mental status, and gait disturbance. We describe a case of Wernicke's encephalopathy in an oncology patient shortly after concurrent 5-fluorouracil, carboplatin, and radiotherapy for locally advanced oropharyngeal cancer, presenting as complete bilateral blindness, ataxia, nystagmus, and confusion. Thiamine was given based on clinical suspicion and rapid improvement of clinical findings occurred. An MRI performed later supported the diagnosis of Wernicke's encephalopathy. A multifactorial etiology of thiamine deficiency from nutritional deficits and neurotoxic effects of chemotherapy are hypothesized. PMID:26623207

  12. [Certain aspects of neoadjuvant therapy of locally advanced breast cancer].

    PubMed

    Voznyĭ, E K; Gurov, S N; Dobrovol'skaia, N Iu

    2001-01-01

    The paper presents the results of a complex investigation of patients with locally-advanced breast cancer who received neoadjuvant chemotherapy or chemoradiation at initial stage. The clinical and pathomorphological effects, nature of neoadjuvant therapy and number of courses were followed up for 5- and 10-year periods. A direct correlation was found between number of courses for chemotherapy-sensitive patients, on the one hand, and greater effect, more intensive medicinal pathomorphism and longer recurrence-free survival, particularly, at later stages, on the other. PMID:11826490

  13. Hepatocellular adenoma: An update

    PubMed Central

    Vijay, Adarsh; Elaffandi, Ahmed; Khalaf, Hatem

    2015-01-01

    Hepatocellular adenomas (HCA) are rare benign liver tumors. Recent technological advancements have helped in the early identification of such lesions. However, precise diagnosis of hepatocellular incidentalomas remains challenging. Studies at the molecular level have provided new insights into the genetics and pathophysiology of these lesions. These in turn have raised questions over their existing management modalities. However, the rarity of the tumor still restricts the quality of evidence available for current recommendations and guidelines. This article provides a comprehensive review on the etiology, molecular biology, patho-physiology, clinical manifestations, and complications associated with HCA. It also elaborates on the genetic advancements, existing diagnostic tools and current guidelines for management for such lesions. PMID:26557953

  14. A Review of Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer

    PubMed Central

    Li, Yi; Wang, Ji; Ma, Xiaowei; Tan, Li; Yan, Yanli; Xue, Chaofan; Hui, Beina; Liu, Rui; Ma, Hailin; Ren, Juan

    2016-01-01

    Neoadjuvant chemoradiotherapy has become the standard treatment for locally advanced rectal cancer. Neoadjuvant chemoradiotherapy not only can reduce tumor size and recurrence, but also increase the tumor resection rate and anus retention rate with very slight side effect. Comparing with preoperative chemotherapy, preoperative chemoradiotherapy can further reduce the local recurrence rate and downstage. Middle and low rectal cancers can benefit more from neoadjuvant chemradiotherapy than high rectal cancer. It needs to refine the selection of appropriate patients and irradiation modes for neoadjuvant chemoradiotherapy. Different therapeutic reactions to neoadjuvant chemoradiotherapy affect the type of surgical techniques, hence calling for the need of much attention. Furthermore, many problems such as accurate staging before surgery, selection of suitable neoadjuvant chemoradiotherapy method, and sensitivity prediction to preoperative radiotherapy need to be well settled. PMID:27489505

  15. Intraoperative and external beam irradiation for locally advanced colorectal cancer.

    PubMed Central

    Gunderson, L L; Martin, J K; Bèart, R W; Nagorney, D M; Fieck, J M; Wieand, H S; Martinez, A; O'Connell, M J; Martenson, J A; McIlrath, D C

    1988-01-01

    In view of poor local control rates obtained with standard treatment, intraoperative radiation (IORT) using electrons was combined with external beam irradiation and surgical resection, with or without 5-fluorouracil (5FU), in 51 patients with locally advanced colorectal cancer (recurrent, 36 patients; primary, 15 patients). Patients received 4500-5500 cGy (rad) of fractionated, multiple field external beam irradiation and an IORT dose of 1000-2000 cGy. Thirty of 51 patients (59%) are alive and 22 patients (43%) are free of disease. In 44 patients at risk greater than or equal to 1 year, local progression within the IORT field has occurred in 1 of 44 (2%) and within the external beam field in 8 of 44 (18%). All local failures have occurred in patients with recurrence or with gross residual after partial resection, and the risk was less in patients who received 5FU during external irradiation (1 of 11, 9% vs. 6 of 31, 19%). The incidence of distant metastases is high in patients with recurrence, but subsequent peritoneal failures are infrequent. Acute and chronic tolerance have been acceptable, but peripheral nerve appears to be a dose-limiting structure. Randomized trials are needed to determine whether potential gains with IORT are real. PMID:3337561

  16. Experience with fast neutron therapy for locally advanced sarcomas

    SciTech Connect

    Salinas, R.; Hussey, D.H.; Fletcher, G.H.; Lindberg, R.D.; Martin, R.G.; Peters, L.J.; Sinkovics, J.G.

    1980-03-01

    Between October 1972 and April 1978, 34 patients with locally advanced sarcomas were treated with fast neutrons using the Texas A and M variable energy cyclotron. The clinical material included 29 patients with soft tissue sarcomas, 4 with chondrosarcomas, and one with an osteosarcoma. The best results were achieved for patients with soft tissue sarcomas; 69% (20/29) had local control of their tumor. Only one of 4 patients with chondrosarcomas was classified as having local tumor control, and one patient with osteosarcoma had persistent disease. With most fractionation schedules, local tumor control was superior for patients who received doses greater than 6500 rad/sub eq/ (2100 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons). The incidence of major complications was notably increased when maximum radiation doses of 7500 rad/sub eq/ or greater were administered (2400 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons). In patients who underwent subsequent surgery, healing was satisfactory if the maximum radiation dose was limited to 4500 to 5500 rad/sub eq/(1450 to 1775 rad/sub n..gamma../ with 50 MeV/sub d ..-->.. Be/ neutrons).

  17. Proton beam therapy for locally advanced lung cancer: A review

    PubMed Central

    Schild, Steven E; Rule, William G; Ashman, Jonathan B; Vora, Sujay A; Keole, Sameer; Anand, Aman; Liu, Wei; Bues, Martin

    2014-01-01

    Protons interact with human tissue differently than do photons and these differences can be exploited in an attempt to improve the care of lung cancer patients. This review examines proton beam therapy (PBT) as a component of a combined modality program for locally advanced lung cancers. It was specifically written for the non-radiation oncologist who desires greater understanding of this newer treatment modality. This review describes and compares photon (X-ray) radiotherapy (XRT) to PBT. The physical differences of these beams are described and the clinical literature is reviewed. Protons can be used to create treatment plans delivering significantly lower doses of radiation to the adjacent organs at risk (lungs, esophagus, and bone marrow) than photons. Clinically, PBT combined with chemotherapy has resulted in low rates of toxicity compared to XRT. Early results suggest a possible improvement in survival. The clinical results of proton therapy in lung cancer patients reveal relatively low rates of toxicity and possible survival benefits. One randomized study is being performed and another is planned to clarify the clinical differences in patient outcome for PBT compared to XRT. Along with the development of better systemic therapy, newer forms of radiotherapy such as PBT should positively impact the care of lung cancer patients. This review provides the reader with the current status of this new technology in treating locally advanced lung cancer. PMID:25302161

  18. Expression of P53 and HSP70 in Chronic Hepatitis, Liver Cirrhosis, and Early and Advanced Hepatocellular Carcinoma Tissues and Their Diagnostic Value in Hepatocellular Carcinoma: An Immunohistochemical Study

    PubMed Central

    Wang, Zhi; Gou, Wenbin; Liu, Ming; Sang, Wei; Chu, Hui; Zhang, Wei

    2015-01-01

    Background Tumor protein (P53) and heat shock protein 70 (HSP70) play key roles in chronic liver diseases. This study aimed to characterize P53 and HSP70 expression in chronic hepatitis (CH), liver cirrhosis (LC), early and advanced HCC, and to analyze their diagnostic value in hepatocellular carcinoma (HCC). Material/Methods Immunohistochemical staining was conducted to evaluate the expression of P53 and HSP70 in 200 human liver tissue specimens, with advanced HCC (n=80), early HCC (n=30), CH (n=30), LC (n=30), and Controls (n=30). Results P53 expression levels were lower in LC than those of HCC, but remained on par with those of CH and Controls. HSP70 expression levels were higher in HCC than those of LC, CH, and Controls. The sensitivity and specificity for HCC diagnosis were: 50.9% and 98.9% for P53, and 78.2 and 77.8% for HSP70, respectively. The sensitivity and specificity of different combinations were: 95.5% and 85.5% with either P53 or HSP70 being positive, and 33.6% and 98.9% if both were positive. Among the differentiation stages marked low, intermediate, and high in HCC, the P53 positive rate was higher in the low than in the intermediate, which was higher than that in the high. HSP70 positive rate was higher in the low and the intermediate than in the high, but no obvious changes were found between the low and the intermediate. Conclusions P53 and HSP70 could be potential biomarkers for HCC diagnosis, and proper combinations of these 2 markers could improve diagnostic accuracy. PMID:26494212

  19. Biomarkers for Hepatocellular Carcinoma

    PubMed Central

    Behne, Tara; Copur, M. Sitki

    2012-01-01

    The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains challenging. Increased understanding of cancer biology and technological advances have enabled identification of a multitude of pathological, genetic, and molecular events that drive hepatocarcinogenesis leading to discovery of numerous potential biomarkers in this disease. They are currently being aggressively evaluated to establish their value in early diagnosis, optimization of therapy, reducing the emergence of new tumors, and preventing the recurrence after surgical resection or liver transplantation. These markers not only help in prediction of prognosis or recurrence but may also assist in deciding appropriate modality of therapy and may represent novel potential targets for therapeutic interventions. In this paper, a summary of most relevant available data from published papers reporting various tissue and serum biomarkers involved in hepatocellular carcinoma was presented. PMID:22655201

  20. Biomarkers for hepatocellular carcinoma.

    PubMed

    Behne, Tara; Copur, M Sitki

    2012-01-01

    The hepatocellular carcinoma (HCC) is one of the most common malignant tumors and carries a poor survival rate. The management of patients at risk for developing HCC remains challenging. Increased understanding of cancer biology and technological advances have enabled identification of a multitude of pathological, genetic, and molecular events that drive hepatocarcinogenesis leading to discovery of numerous potential biomarkers in this disease. They are currently being aggressively evaluated to establish their value in early diagnosis, optimization of therapy, reducing the emergence of new tumors, and preventing the recurrence after surgical resection or liver transplantation. These markers not only help in prediction of prognosis or recurrence but may also assist in deciding appropriate modality of therapy and may represent novel potential targets for therapeutic interventions. In this paper, a summary of most relevant available data from published papers reporting various tissue and serum biomarkers involved in hepatocellular carcinoma was presented. PMID:22655201

  1. Postmastectomy radiotherapy for locally advanced breast cancer receiving neoadjuvant chemotherapy.

    PubMed

    Meattini, Icro; Cecchini, Sara; Di Cataldo, Vanessa; Saieva, Calogero; Francolini, Giulio; Scotti, Vieri; Bonomo, Pierluigi; Mangoni, Monica; Greto, Daniela; Nori, Jacopo; Orzalesi, Lorenzo; Casella, Donato; Simoncini, Roberta; Fambrini, Massimiliano; Bianchi, Simonetta; Livi, Lorenzo

    2014-01-01

    Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (range 2-16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7-12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥ 4 positive nodes (HR 5.0, 1.51-16.52; P = 0.035), extracapsular extension (HR 2.18, 1.37-3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57, 0.36-0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P = 0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy. PMID:25045694

  2. Chemotherapy in locally advanced head and neck squamous cell carcinoma.

    PubMed

    Gyawali, Bishal; Shimokata, Tomoya; Honda, Kazunori; Ando, Yuichi

    2016-03-01

    Chemotherapy, in combination with a local treatment, has a role in nearly all the settings of locally advanced head and neck squamous cell carcinoma (LAHNSCC) treatment: as definitive, adjuvant or induction therapy. However, despite many years of trials, controversies still exist regarding the best approach to using chemotherapy in the multi-modal treatment of LAHNSCC. Opinions are divided on sequential versus concurrent use of chemotherapy and radiotherapy for unresectable LAHNSCC. More debate exists on whether the addition of induction chemotherapy to concomitant chemoradiotherapy is clinically meaningful. After the approval of cetuximab in combination with radiotherapy for this disease, making treatment choices have become further complicated. Although new data from trials are arriving every year, the results have been inconclusive. In this review, we provide the readers with the latest information on various strategies of using chemotherapy and cetuximab that will help to make an evidence-based decision in the treatment of LAHNSCC, including the approach to larynx preservation. We conclude that with the available information, concurrent chemoradiotherapy should be preferred over induction chemotherapy, except in the setting of larynx preservation. Furthermore, given the paucity of positive data and severe financial toxicity associated with cetuximab, concurrent chemoradiotherapy should be the preferred choice over cetuximab-radiotherapy. Future trials in head and neck cancer should be properly planned to address these controversies and provide clear solutions. PMID:26924194

  3. Locally Advanced Breast Cancer: Autologous Versus Implant-based Reconstruction

    PubMed Central

    Prousskaia, Elena; Chow, Whitney; Angelaki, Anna; Cirwan, Cleona; Hamed, Hisham; Farhadi, Jian

    2016-01-01

    Background: Recent papers and guidelines agree that patients with locally advanced breast cancer (LABC) should be offered breast reconstruction. Yet, the type of reconstruction in this group of patients is still a point of controversy. Methods: One hundred fourteen patients, treated for LABC from 2007 to 2013, were divided into 3 groups based on the reconstructive option: no reconstruction (NR), implant-based/expander-based reconstruction (IBR), and autologous tissue reconstruction (ATR). We analyzed demographics and compared delay in adjuvant therapy, length of hospitalization, surgical complications, failure of reconstruction, local recurrence, and disease-free survival. Results: Twenty-six patients had NR, 38 had IBR, and 50 had ATR. No significant difference was found in the percentage of patients who had their adjuvant treatment delayed [16% (NR) vs 22% (IBR) vs 14% (ATR)]. Mean length of hospitalization for the NR, IBR, and ATR groups was 2.7, 6, and 7.5 days, respectively. Complication rates requiring readmission were 36% (NR), 42% (IBR), and 32% (ATR). In the IBR group, 37% of implants were removed because of complications. Failure of reconstruction was 37% and 0% for the IBR and ATR groups, respectively. Local recurrence rates in the NR and Reconstruction (groups IBR and ATR combined) groups were 7% and 2%, respectively. Mean survival times in patients were 18 (NR), 10.3 (IBR), and 12.2 (ATR) months. Conclusions: No significant difference was found in the hospital stay length, adjuvant treatment delay, and complication rates between IBR and ATR. High rates of failed reconstruction suggest that the use of implants should be considered very carefully in patients with LABC. PMID:27014551

  4. A block matching-based registration algorithm for localization of locally advanced lung tumors

    PubMed Central

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-01-01

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm3), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%; p < 0.001). Left

  5. A block matching-based registration algorithm for localization of locally advanced lung tumors

    SciTech Connect

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2014-04-15

    Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

  6. [Neoadjuvant radiochemotherapy in the treatment of locally advanced rectal tumors].

    PubMed

    Rápolti, Edit; Szigeti, András; Farkas, Róbert; Bellyei, Szabolcs; Boronkai, Arpád; Papp, András; Gömöri, Eva; Horváth, Ors Péter; Mangel, László

    2009-12-01

    We investigated the response rate and side effects of simultaneous, neoadjuvant radiochemotherapy (RCT) in locally advanced rectal cancer. Between 2005 and 2007, we treated 112 patients in stage II-III rectal carcinoma at the Institute of Oncotherapy, University of Pécs. For staging abdomino-pelvic CT (112) and transrectal US (49) or pelvic MR (10), or PET-CT (1) was performed. Radiation therapy was delivered with 3D CRT-based technique using belly-board with 18 MV photon energy, while patients in prone position. A total dose of 45 Gy (single dose 1.8 Gy) was delivered to the tumor and the pelvic lymph nodes. 5-FU and Ca-folinate was administered concomitantly in the 1st and 5th week of radiotherapy. Four weeks after delivering neoadjuvant RCT the patients' control CT was evaluated according to RECIST criteria. RCT was followed by surgery in 6-9 weeks. We graded the histology using the Mandard regression score system. Side effects were registered using CTCAE v 3.0. Grade 1, 2 or 3 acute gastrointestinal toxicity occurred in 12%, grade 3 hematological toxicity in 9.5% of the patients. The response rate determined by using control CT was 64.85%. According to the Mandard regression score, TRG1 occurred in 15%, TRG2 in 30.4%, TRG3 in 28%, TRG4 in 24% and TRG5 in 2.6% of the cases. Radical surgery was performed in 89 cases, 72 with R0 resection. By assessing the histological samples we found downstaging in 46% of the T and 34.5% of the N stage. We have no information on increased postoperative complications. We followed 86 patients after neoadjuvant therapy. Until March 2009 there was no progression in 48 of our patients. In 13 cases local relapse occurred, and in 25 cases the disease progressed because of distant metastasis, although local control was maintained. 10 patients had local relapse and distant metastases. 17 patients passed away. As a conclusion, neoadjuvant RCT of Stage II-III patients is an effective and well tolerated treatment, allowing for high R0

  7. Prospects for Observing and Localizing Gravitational-Wave Transients with Advanced LIGO and Advanced Virgo

    NASA Astrophysics Data System (ADS)

    Abbott, B. P.; Abbott, R.; Abbott, T. D.; Abernathy, M. R.; Acernese, F.; Ackley, K.; Adams, C.; Adams, T.; Addesso, P.; Adhikari, R. X.; Adya, V. B.; Affeldt, C.; Agathos, M.; Agatsuma, K.; Aggarwal, N.; Aguiar, O. D.; Ain, A.; Ajith, P.; Allen, B.; Allocca, A.; Altin, P. A.; Amariutei, D. V.; Anderson, S. B.; Anderson, W. G.; Arai, K.; Araya, M. C.; Arceneaux, C. C.; Areeda, J. S.; Arnaud, N.; Arun, K. G.; Ashton, G.; Ast, M.; Aston, S. M.; Astone, P.; Aufmuth, P.; Aulbert, C.; Babak, S.; Baker, P. T.; Baldaccini, F.; Ballardin, G.; Ballmer, S. W.; Barayoga, J. C.; Barclay, S. E.; Barish, B. C.; Barker, D.; Barone, F.; Barr, B.; Barsotti, L.; Barsuglia, M.; Barta, D.; Bartlett, J.; Bartos, I.; Bassiri, R.; Basti, A.; Batch, J. C.; Baune, C.; Bavigadda, V.; Bazzan, M.; Behnke, B.; Bejger, M.; Belczynski, C.; Bell, A. S.; Bell, C. J.; Berger, B. K.; Bergman, J.; Bergmann, G.; Berry, C. P. L.; Bersanetti, D.; Bertolini, A.; Betzwieser, J.; Bhagwat, S.; Bhandare, R.; Bilenko, I. A.; Billingsley, G.; Birch, J.; Birney, R.; Biscans, S.; Bisht, A.; Bitossi, M.; Biwer, C.; Bizouard, M. A.; Blackburn, J. K.; Blair, C. D.; Blair, D.; Blair, R. M.; Bloemen, S.; Bock, O.; Bodiya, T. P.; Boer, M.; Bogaert, G.; Bogan, C.; Bohe, A.; Bojtos, P.; Bond, C.; Bondu, F.; Bonnand, R.; Bork, R.; Boschi, V.; Bose, S.; Bozzi, A.; Bradaschia, C.; Brady, P. R.; Braginsky, V. B.; Branchesi, M.; Brau, J. E.; Briant, T.; Brillet, A.; Brinkmann, M.; Brisson, V.; Brockill, P.; Brooks, A. F.; Brown, D. A.; Brown, D. D.; Brown, N. M.; Buchanan, C. C.; Buikema, A.; Bulik, T.; Bulten, H. J.; Buonanno, A.; Buskulic, D.; Buy, C.; Byer, R. L.; Cadonati, L.; Cagnoli, G.; Cahillane, C.; Calderón Bustillo, J.; Callister, T.; Calloni, E.; Camp, J. B.; Cannon, K. C.; Cao, J.; Capano, C. D.; Capocasa, E.; Carbognani, F.; Caride, S.; Casanueva Diaz, J.; Casentini, C.; Caudill, S.; Cavaglià, M.; Cavalier, F.; Cavalieri, R.; Cella, G.; Cepeda, C.; Cerboni Baiardi, L.; Cerretani, G.; Cesarini, E.; Chakraborty, R.; Chalermsongsak, T.; Chamberlin, S. J.; Chan, M.; Chao, S.; Charlton, P.; Chassande-Mottin, E.; Chen, H. Y.; Chen, Y.; Cheng, C.; Chincarini, A.; Chiummo, A.; Cho, H. S.; Cho, M.; Chow, J. H.; Christensen, N.; Chu, Q.; Chua, S.; Chung, S.; Ciani, G.; Clara, F.; Clark, J. A.; Cleva, F.; Coccia, E.; Cohadon, P.-F.; Colla, A.; Collette, C. G.; Constancio, M.; Conte, A.; Conti, L.; Cook, D.; Corbitt, T. R.; Cornish, N.; Corsi, A.; Cortese, S.; Costa, C. A.; Coughlin, M. W.; Coughlin, S. B.; Coulon, J.-P.; Countryman, S. T.; Couvares, P.; Coward, D. M.; Cowart, M. J.; Coyne, D. C.; Coyne, R.; Craig, K.; Creighton, J. D. E.; Cripe, J.; Crowder, S. G.; Cumming, A.; Cunningham, L.; Cuoco, E.; Dal Canton, T.; Danilishin, S. L.; D'Antonio, S.; Danzmann, K.; Darman, N. S.; Dattilo, V.; Dave, I.; Daveloza, H. P.; Davier, M.; Davies, G. S.; Daw, E. J.; Day, R.; DeBra, D.; Debreczeni, G.; Degallaix, J.; De Laurentis, M.; Deléglise, S.; Del Pozzo, W.; Denker, T.; Dent, T.; Dereli, H.; Dergachev, V.; DeRosa, R.; De Rosa, R.; DeSalvo, R.; Dhurandhar, S.; Díaz, M. C.; Di Fiore, L.; Di Giovanni, M.; Di Lieto, A.; Di Palma, I.; Di Virgilio, A.; Dojcinoski, G.; Dolique, V.; Donovan, F.; Dooley, K. L.; Doravari, S.; Douglas, R.; Downes, T. P.; Drago, M.; Drever, R. W. P.; Driggers, J. C.; Du, Z.; Ducrot, M.; Dwyer, S. E.; Edo, T. B.; Edwards, M. C.; Effler, A.; Eggenstein, H.-B.; Ehrens, P.; Eichholz, J. M.; Eikenberry, S. S.; Engels, W.; Essick, R. C.; Etzel, T.; Evans, M.; Evans, T. M.; Everett, R.; Factourovich, M.; Fafone, V.; Fair, H.; Fairhurst, S.; Fan, X.; Fang, Q.; Farinon, S.; Farr, B.; Farr, W. M.; Favata, M.; Fays, M.; Fehrmann, H.; Fejer, M. M.; Ferrante, I.; Ferreira, E. C.; Ferrini, F.; Fidecaro, F.; Fiori, I.; Fisher, R. P.; Flaminio, R.; Fletcher, M.; Fournier, J.-D.; Franco, S.; Frasca, S.; Frasconi, F.; Frei, Z.; Freise, A.; Frey, R.; Fricke, T. T.; Fritschel, P.; Frolov, V. V.; Fulda, P.; Fyffe, M.; Gabbard, H. A. G.; Gair, J. R.; Gammaitoni, L.; Gaonkar, S. G.; Garufi, F.; Gatto, A.; Gaur, G.; Gehrels, N.; Gemme, G.; Gendre, B.; Genin, E.; Gennai, A.; George, J.; Gergely, L.; Germain, V.; Ghosh, A.; Ghosh, S.; Giaime, J. A.; Giardina, K. D.; Giazotto, A.; Gill, K.; Glaefke, A.; Goetz, E.; Goetz, R.; Gondan, L.; González, G.; Gonzalez Castro, J. M.; Gopakumar, A.; Gordon, N. A.; Gorodetsky, M. L.; Gossan, S. E.; Gosselin, M.; Gouaty, R.; Graef, C.; Graff, P. B.; Granata, M.; Grant, A.; Gras, S.; Gray, C.; Greco, G.; Green, A. C.; Groot, P.; Grote, H.; Grunewald, S.; Guidi, G. M.; Guo, X.; Gupta, A.; Gupta, M. K.; Gushwa, K. E.; Gustafson, E. K.; Gustafson, R.; Hacker, J. J.; Hall, B. R.; Hall, E. D.; Hammond, G.; Haney, M.; Hanke, M. M.; Hanks, J.; Hanna, C.; Hannam, M. D.; Hanson, J.; Hardwick, T.; Harms, J.; Harry, G. M.; Harry, I. W.; Hart, M. J.

    2016-02-01

    We present a possible observing scenario for the Advanced LIGO and Advanced Virgo gravitational-wave detectors over the next decade, with the intention of providing information to the astronomy community to facilitate planning for multi-messenger astronomy with gravitational waves. We determine the expected sensitivity of the network to transient gravitational-wave signals, and study the capability of the network to determine the sky location of the source. We report our findings for gravitational-wave transients, with particular focus on gravitational-wave signals from the inspiral of binary neutron-star systems, which are considered the most promising for multi-messenger astronomy. The ability to localize the sources of the detected signals depends on the geographical distribution of the detectors and their relative sensitivity, and 90% credible regions can be as large as thousands of square degrees when only two sensitive detectors are operational. Determining the sky position of a significant fraction of detected signals to areas of 5 deg^2 to 20 deg^2 will require at least three detectors of sensitivity within a factor of ~2 of each other and with a broad frequency bandwidth. Should the third LIGO detector be relocated to India as expected, a significant fraction of gravitational-wave signals will be localized to a few square degrees by gravitational-wave observations alone.

  8. Postmastectomy Radiotherapy for Locally Advanced Breast Cancer Receiving Neoadjuvant Chemotherapy

    PubMed Central

    Meattini, Icro; Di Cataldo, Vanessa; Saieva, Calogero; Francolini, Giulio; Scotti, Vieri; Bonomo, Pierluigi; Mangoni, Monica; Greto, Daniela; Nori, Jacopo; Orzalesi, Lorenzo; Casella, Donato; Simoncini, Roberta; Fambrini, Massimiliano; Bianchi, Simonetta; Livi, Lorenzo

    2014-01-01

    Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a single-center series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated with NAC and mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At a median follow-up period of 7.7 years (range 2–16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7–12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were ≥4 positive nodes (HR 5.0, 1.51–16.52; P = 0.035), extracapsular extension (HR 2.18, 1.37–3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57, 0.36–0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P = 0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy. PMID:25045694

  9. Metastatic Hepatocellular Carcinoma Responsive to Pembrolizumab

    PubMed Central

    Truong, Phu; Kallail, K. James

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs with chronic liver disease. Surgical resection is the mainstay of therapy for localized disease whereas therapeutic options for advanced disease are limited. The innovative blockade of immune checkpoints with targeted immunotherapies, such as monoclonal antibodies against programmed death receptor 1 (PD-1), have shown promise in the treatment of solid malignancies. The PD-1 inhibiting antibodies, nivolumab and pembrolizumab prolonged overall survival in randomized trials in metastatic melanoma and advanced non-small cell lung cancer. This is a report of a 75-year-old male patient with metastatic HCC who was initially treated with the standard of therapy sorafenib. After failure of sorafenib therapy, pembrolizumab was started. There was a dramatic response to pembrolizumab with decrease in tumor size and drop in alfa fetoprotein. To the best of our knowledge, this is the first case report of metastatic HCC responsive to pembrolizumab after failure of sorafenib. PMID:27433410

  10. Phase I study of tivantinib in Japanese patients with advanced hepatocellular carcinoma: Distinctive pharmacokinetic profiles from other solid tumors.

    PubMed

    Okusaka, Takuji; Aramaki, Takeshi; Inaba, Yoshitaka; Nakamura, Shinichiro; Morimoto, Manabu; Moriguchi, Michihisa; Sato, Takashi; Ikawa, Yuta; Ikeda, Masafumi; Furuse, Junji

    2015-05-01

    A c-Met inhibitor tivantinib is a candidate anticancer agent for patients with hepatocellular carcinoma (HCC), and CYP2C19 is the key metabolic enzyme for tivantinib. Previous Japanese phase I studies in patients with solid tumors (except HCC) recommend 360 mg twice daily (BID) and 240 mg BID for CYP2C19 extensive metabolizers (EM) and poor metabolizers (PM), respectively. In this study, Japanese patients with HCC in whom sorafenib treatment has failed were enrolled to evaluate the safety, tolerability and pharmacokinetics of oral tivantinib as a single agent. The dose was escalated separately in EM and PM, from 120 mg BID to 240 mg BID, in both capsule and tablet formulations. A total of 28 patients (EM: 21, PM: 7) received tivantinib. At a dose of 120 mg BID, dose-limiting toxicities (DLT) did not develop in 12 EM (capsule: 6, tablet: 6) and 7 PM (capsule: 4, tablet: 3) during the DLT-observation period (for 29 days after first dosing). At this dose, the pharmacokinetic profiles of tivantinib (AUC0-12 and Cmax ) did not remarkably differ between EM and PM. When treated with 240 mg BID, 5 of 9 EM (capsule: 4 of 6, tablet: 1 of 3) developed neutropenia-related DLT accompanying plasma tivantinib concentration higher than expected from the previous studies. Consequently, PM did not receive 240 mg BID. In conclusion, 120 mg BID of tivantinib is recommended among Japanese patients with HCC regardless of CYP2C19 phenotype. PMID:25711511

  11. Hypofractionated ablative radiotherapy for locally advanced pancreatic cancer

    PubMed Central

    Crane, Christopher H.

    2016-01-01

    The role of radiation in locally advanced unresectable pancreatic cancer (LAPC) is controversial. Randomized trials evaluating standard doses of chemoradiation have not shown a significant benefit from the use of consolidative radiation. Results from non-randomized studies of 3–5-fraction stereotactic body radiotherapy (SBRT) have been similar to standard chemoradiation, but with less toxicity and a shorter treatment time. Doses of SBRT have been reduced to subablative levels for the sake of tolerability. The benefit of both options is unclear. In contrast, ablative doses can be delivered using an SBRT technique in 15–28 fractions. The keys to the delivery of ablative doses are computed tomography (CT) image guidance and respiratory gating. Higher doses have resulted in encouraging long-term survival results. In this review, we present a comprehensive solution to achieving ablative doses for selected patients with pancreatic tumors by using a combination of classical, modern and novel concepts of radiotherapy: fractionation, CT image guidance, respiratory gating, intentional dose heterogeneity, and simultaneous integrated protection. PMID:27029741

  12. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Portal Vein Thrombosis: Impact of Early Response to 4 Weeks of Treatment

    PubMed Central

    Lin, Chen-Chun; Hung, Chien-Fu; Chen, Wei-Ting; Lin, Shi-Ming

    2015-01-01

    Aim The aim of the study was to investigate the impact of early response (ER) to hepatic arterial infusion chemotherapy (HAIC) on outcomes of patients with advanced hepatocellular carcinoma (HCC) complicated with major portal vein tumor thrombosis (PVTT). Methods Thirty-nine patients receiving HAIC with low-dose cisplatin, 5-fluorouracil (5FU), and leucovorin were enrolled. One course of HAIC consisted of 5 days of treatment and 2 days rest per week for 4 consecutive weeks. ER was categorized as complete response, partial response, or minor response and was determined by World Health Organization criteria with dynamic computed tomography findings performed within 1 week after the first course of HAIC. Results Thirteen (33%) patients achieved an ER. Twelve (92.3%) of these 13 ER patients achieved a higher overall response than all but one (3.8%) of the 26 non-early responders (NERs) (p<0.001). ER was the exclusive independent favorable factor for survival (p=0.003). Downstaging of tumors was noted in 76.9% of ERs, and these patients could proceed to locoregional therapies. ER patients subsequently had a higher 1-year survival (76.9% vs. 3.8%, p<0.001) and 6-month progression-free survival (PFS) (84.6% vs. 15.4%, p<0.001) than those for NERs. Only 8% of patients experienced grade 3 or higher toxicity during the first 4-week course of HAIC. Conclusions HAIC can yield a satisfactory ER for advanced HCC with PVTT. Moreover, achievement of ER after HAIC in advanced HCC with PVTT is strongly associated with better overall survival and PFS. PMID:26734578

  13. Evaluation of sorafenib treatment and hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: a comparative study using the propensity score matching method

    PubMed Central

    Fukubayashi, Kotaro; Tanaka, Motohiko; Izumi, Kazuhiro; Watanabe, Takehisa; Fujie, Satomi; Kawasaki, Takeshi; Yoshimaru, Yoko; Tateyama, Masakuni; Setoyama, Hiroko; Naoe, Hideaki; Kikuchi, Ken; Sasaki, Yutaka

    2015-01-01

    While sorafenib (SFN) is the established worldwide standard therapeutic agent for advanced hepatocellular carcinoma (HCC), hepatic arterial infusion chemotherapy (HAIC) is also considered a favorable treatment for some advanced HCCs. This study aimed to evaluate each treatment and provide an optimal therapeutic choice for advanced HCCs. We analyzed 72 patients treated with SFN and 128 patients receiving HAIC. Both treatment groups were analyzed for prognostic and disease progression factors, and matched pair analysis was performed using the propensity score matching method. The preferable status of intrahepatic lesions, that is, no lesions or only a single (<3 cm) intrahepetic lesion, was positively associated with good prognosis and negatively associated with disease progression in the SFN group. Maximum tumor size (>5 cm) and low albumin (≤3.4 g/dL) were poor prognostic and disease progression factors in the HAIC group. Analysis of 53 patients selected from each of the SFN and HAIC groups based on the propensity score matching method showed no significant differences in survival or disease progression between the two matched subgroups. On the other hand, progression-free survival (PFS) in the HAIC-matched subgroup was significantly longer than in the SFN-matched subgroup, particularly in patients with portal vein invasion (PVI) and/or without extrahepatic spread (EHS). The treatment efficacy of HAIC is similar to that of SFN regarding survival and disease progression. Longer PFS might be expected for HAIC compared with SFN, particularly in patients with PVI and/or without EHS. PMID:26044168

  14. Efficacy of combination treatment modalities for intermediate and advanced hepatocellular carcinoma: intra-arterial therapies, sorafenib and novel small molecules

    PubMed Central

    Gutierrez, Julio A.; Gish, Robert G.

    2015-01-01

    Hepatocellular carcinoma (HCC) is a growing epidemic with a high mortality rate and clear need for improved therapies. In patients with Barcelona-Clinic Liver Cancer (BCLC) B and C, treatment with transarterial chemoembolization (TACE) has been the gold standard in therapy as it delays progression; however, recurrence proves common. In the US, transarterial bead embolization (TABE) has uniformly replaced TACE. With this limited armamentarium, there is need for a shift to novel strategies combining different modalities to further improve patient outcomes. Historically, HCC drug discovery concentrated on common features of HCC including its highly vascular nature and dependence on growth factors (GFs). The multikinase inhibitor sorafenib acts on angiogenesis via modulation of vascular endothelial GF expression and was the first step toward systemic targeted therapy against HCC. Sorafenib has provided clinicians with a tool to modestly improve survival by 2–6 months or longer. Despite the progress in survival provided by TACE, TABE and sorafenib independently, rigorous combination clinical trials do not consistently show significant improvement over TACE/TABE monotherapy. Other novel small molecules targeting angiogenesis such as brivanib, linifanib and everolimus have failed or are in development. Anti-HCV treatment became more feasible with the novel direct-acting antiviral agents; with the much higher and more durable treatment responses that they provide, the risk of HCC progression may be reduced. The most effective strategies in developing combination therapies are hampered by the complexities of FDA testing along with intellectual property and economic issues. To achieve significant progress, more basic science studies are necessary to help understand which novel molecules demonstrate the greatest synergy. Individual patient genomic profiling and biomarkers may help guide therapy and improve the clinician’s ability to tailor treatment and to know when it

  15. Presentation of hepatocellular antigens

    PubMed Central

    Grakoui, Arash; Crispe, Ian Nicholas

    2016-01-01

    The liver is an organ in which antigen-specific T-cell responses manifest a bias toward immune tolerance. This is clearly seen in the rejection of allogeneic liver transplants, and multiple other phenomena suggest that this effect is more general. These include tolerance toward antigens introduced via the portal vein, immune failure to several hepatotropic viruses, the lack of natural liver-stage immunity to malaria parasites, and the frequent metastasis of cancers to the liver. Here we review the mechanisms by which T cells engage with hepatocellular antigens, the context in which such encounters occur, and the mechanisms that act to suppress a full T-cell response. While many mechanisms play a role, we will argue that two important processes are the constraints on the cross-presentation of hepatocellular antigens, and the induction of negative feedback inhibition driven by interferons. The constant exposure of the liver to microbial products from the intestine may drive innate immunity, rendering the local environment unfavorable for specific T-cell responses through this mechanism. Nevertheless, tolerance toward hepatocellular antigens is not monolithic and under specific circumstances allows both effective immunity and immunopathology. PMID:26924525

  16. Clinical Trial Simulations From a Model‐Based Meta‐Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy

    PubMed Central

    Chen, Y; Pithavala, YK; Nickens, DJ; Valota, O; Amantea, MA

    2016-01-01

    A mixed effect model describing median overall survival (mOS) in patients with advanced hepatocellular carcinoma (aHCC) treated with antiangiogenic therapy (AAT) was developed from literature data. Data were extracted from 59 studies, representing 4,813 patients. The final model included estimates of mOS after AAT (8.5 months) or placebo (7.1 months) administration. The mOS increased 21% when the AAT was sorafenib (SOR) or 42% when locoregional therapy was coadministered. The mOS decreased when patients received prior systemic therapy (↓7%) or concomitant chemotherapy (↓4%) or the percentage of patients with hepatitis B increased (↓∼0.4%/%). Clinical trial simulations of a phase II comparative trial predicted an mOS ratio (placebo:AAT) of 0.687 or 0.831, with a 65% or 22% probability of demonstrating superiority, for SOR or other AATs, respectively. Additionally, the 95% confidence interval (CI) of the simulated median mOS ratio for non‐SOR AATs was similar to the 95% CI of the hazard ratio (HR) observed in the trial. PMID:27299940

  17. Clinical Trial Simulations From a Model-Based Meta-Analysis of Studies in Patients With Advanced Hepatocellular Carcinoma Receiving Antiangiogenic Therapy.

    PubMed

    Zierhut, M L; Chen, Y; Pithavala, Y K; Nickens, D J; Valota, O; Amantea, M A

    2016-05-01

    A mixed effect model describing median overall survival (mOS) in patients with advanced hepatocellular carcinoma (aHCC) treated with antiangiogenic therapy (AAT) was developed from literature data. Data were extracted from 59 studies, representing 4,813 patients. The final model included estimates of mOS after AAT (8.5 months) or placebo (7.1 months) administration. The mOS increased 21% when the AAT was sorafenib (SOR) or 42% when locoregional therapy was coadministered. The mOS decreased when patients received prior systemic therapy (↓7%) or concomitant chemotherapy (↓4%) or the percentage of patients with hepatitis B increased (↓∼0.4%/%). Clinical trial simulations of a phase II comparative trial predicted an mOS ratio (placebo:AAT) of 0.687 or 0.831, with a 65% or 22% probability of demonstrating superiority, for SOR or other AATs, respectively. Additionally, the 95% confidence interval (CI) of the simulated median mOS ratio for non-SOR AATs was similar to the 95% CI of the hazard ratio (HR) observed in the trial. PMID:27299940

  18. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

    PubMed Central

    Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  19. The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization

    PubMed Central

    Liu, Lei; Zhao, Yan; Jia, Jia; Chen, Hui; Bai, Wei; Yang, Man; Yin, Zhanxin; He, Chuangye; Zhang, Lei; Guo, Wengang; Niu, Jing; Yuan, Jie; Cai, Hongwei; Xia, Jielai; Fan, Daiming; Han, Guohong

    2016-01-01

    This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2–66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24–3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15–2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy. PMID:26831408

  20. The Prognostic Value of Alpha-Fetoprotein Response for Advanced-Stage Hepatocellular Carcinoma Treated with Sorafenib Combined with Transarterial Chemoembolization.

    PubMed

    Liu, Lei; Zhao, Yan; Jia, Jia; Chen, Hui; Bai, Wei; Yang, Man; Yin, Zhanxin; He, Chuangye; Zhang, Lei; Guo, Wengang; Niu, Jing; Yuan, Jie; Cai, Hongwei; Xia, Jielai; Fan, Daiming; Han, Guohong

    2016-01-01

    This retrospective cohort study aimed to evaluate the prognostic value of the alpha-fetoprotein (AFP) response in advanced-stage hepatocellular carcinoma (HCC) patients treated with sorafenib combined with transarterial chemoembolization. From May 2008 to July 2012, 118 HCC patients with baseline AFP levels >20 ng/ml treated with combination therapy were enrolled. A receiver operating characteristic curve was used to generate a cutoff point for AFP changes for predicting survival. The AFP response was defined as an AFP decrease rate [ΔAFP(%)] greater than the cutoff point. The ΔAFP(%) was defined as the percentage of changes between the baseline and the nadir values within 2 months after therapy. The median follow-up time was 8.8 months (range 1.2-66.9). A level of 46% was chosen as the threshold value for ΔAFP (sensitivity = 53.7%, specificity = 83.3%). The median overall survival was significantly longer in the AFP response group than in the AFP non-response group (12.8 vs. 6.4 months, P = 0.001). Multivariate analysis showed that ECOG ≥ 1 (HR = 1.95; 95% CI 1.24-3.1, P = 0.004) and AFP nonresponse (HR = 1.71; 95% CI 1.15-2.55, P = 0.009) were associated with increased risk of death. In conclusion, AFP response could predict the survival of patients with advanced-stage HCC at an early time point after combination therapy. PMID:26831408

  1. Changes in plasma vascular endothelial growth factor at 8 weeks after sorafenib administration as predictors of survival for advanced hepatocellular carcinoma

    PubMed Central

    Tsuchiya, Kaoru; Asahina, Yasuhiro; Matsuda, Shuya; Muraoka, Masaru; Nakata, Toru; Suzuki, Yuichiro; Tamaki, Nobuharu; Yasui, Yutaka; Suzuki, Shoko; Hosokawa, Takanori; Nishimura, Takashi; Ueda, Ken; Kuzuya, Teiji; Nakanishi, Hiroyuki; Itakura, Jun; Takahashi, Yuka; Kurosaki, Masayuki; Enomoto, Nobuyuki; Izumi, Namiki

    2014-01-01

    Background A new predictive biomarker for determining prognosis in patients with hepatocellular carcinoma (HCC) who receive sorafenib is required, because achieving a reduction in tumor size with sorafenib is rare, even in patients who have a favorable prognosis. Vascular endothelial growth factor (VEGF) receptor is a sorafenib target. In the current study, the authors examined changes in plasma VEGF concentrations during sorafenib treatment and determined the clinical significance of VEGF as a prognostic indicator in patients with HCC. Methods Plasma VEGF concentrations were serially measured in 63 patients with advanced HCC before and during sorafenib treatment. A plasma VEGF concentration that decreased >5% from the pretreatment level at 8 weeks was defined as a “VEGF decrease.” An objective tumor response was determined using modified Response Evaluation Criteria in Solid Tumors 1 month after the initiation of therapy and every 3 months thereafter. Results Patients who had a VEGF decrease at week 8 (n = 14) had a longer median survival than those who did not have a VEGF decrease (n = 49; 30.9 months vs 14.4 months; P = .038). All patients who had a VEGF decrease survived for >6 months, and the patients who had both a VEGF decrease and an α-fetoprotein response (n = 6) survived during the observation period (median, 19.7 months; range, 6.5-31.0 months). In univariate analyses, a VEGF decrease, radiologic findings classified as progressive disease, and major vascular invasion were associated significantly with 1-year survival; and, in multivariate analysis, a VEGF decrease was identified as an independent factor associated significantly with survival. Conclusions A plasma VEGF concentration decrease at 8 weeks after starting sorafenib treatment may predict favorable overall survival in patients with advanced HCC. PMID:24122122

  2. Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

    PubMed

    Hong, Ying-Fen; Chen, Zhan-Hong; Ma, Xiao-Kun; Li, Xing; Wu, Dong-Hao; Chen, Jie; Dong, Min; Wei, Li; Wang, Tian-Tian; Ruan, Dan-Yun; Lin, Ze-Xiao; Wen, Jing-Yun; Lin, Qu; Jia, Chang-Chang; Wu, Xiang-Yuan

    2016-04-01

    Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P < 0.05). When predicting 6-month survival, AUCs of MELD-AS and MELD-NA are significantly higher than those of the other models (P < 0.05). Cutoff point of MELD-AS is 23.11 with 40.5 % sensitivity and 93.8 % specificity at 1 month, 9.5 with 76.9 % sensitivity and 59.5 % specificity at 3 months, and 18.5 with 27.0 % sensitivity and 89.1 % specificity at 6 months. MELD-based scores of death group are significantly higher than those of survivors within 1 and 3 months (P < 0.001). Independent prognostic factors identified by multivariate analysis included persistent ascites, serum sodium, and thrombosis. MELD-AS is the best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients

  3. Hepatocellular carcinoma: From diagnosis to treatment.

    PubMed

    Grandhi, Miral Sadaria; Kim, Amy K; Ronnekleiv-Kelly, Sean M; Kamel, Ihab R; Ghasebeh, Mounes A; Pawlik, Timothy M

    2016-06-01

    Primary liver cancer is the sixth most common cancer overall and the second most common cause of cancer mortality worldwide. Hepatocellular carcinoma accounts for up to 90% of all primary hepatic malignancies and represents a major international health problem. While surgical resection and transplantation are the cornerstone of therapy in early-stage hepatocellular carcinoma, locoregional therapy and sorafenib are beneficial in those with more advanced disease or those who are not surgical candidates. At times, the integration of both surgical and locoregional therapy may be necessary. Hence, hepatocellular carcinoma requires a multidisciplinary approach to determine the most appropriate treatment as well as the timing of various treatments for optimal outcomes. PMID:27312032

  4. p53 mutations and overexpression in locally advanced breast cancers.

    PubMed Central

    Faille, A.; De Cremoux, P.; Extra, J. M.; Linares, G.; Espie, M.; Bourstyn, E.; De Rocquancourt, A.; Giacchetti, S.; Marty, M.; Calvo, F.

    1994-01-01

    Alterations in the p53 gene were analysed in 39 patients with locally advanced breast cancers (LABCs) (stage III-IV) with inflammatory signs in most cases (UICC stage T4d = 32 patients) by molecular and immunohistochemical (IHC) approaches. All patients were included in the same therapy protocol. Using polymerase chain reaction (PCR) and a single-strand conformational polymorphism migration technique (SSCP), the presence of mutations in exons 2-11, covering the entire coding sequence of the p53 gene, was evaluated. Using the mouse specific anti-human p53 monoclonal antibody (PAb 1801), we also looked for overexpression of the p53 protein in tissue sections. In 16 cases shifted bands were reproducibly identified by PCR-SSCP, and all but one (localised to exon 10) were in exons 5-8, the usual mutational hotspots. Fifteen of these 16 samples were sequenced and 14 of the suspected mutations (36%) were confirmed. Most of them (12) were single nucleotide substitutions, and transitions were more frequent (eight cases) than transversions (four cases). Fourteen of the tumour samples were positively stained with the monoclonal antibody PAb 1801, 11 with nuclear staining only, two with mixed cytoplasmic and nuclear staining and one with cytoplasmic staining only. Staining patterns were very heterogeneous in terms of the percentage of positive cells (10-75%) and their distribution in the tissue section (isolated foci or dispersed cells). In 11 of the 14 mutated cases a positive immunostaining was observed. The presence of a p53 mutation was significantly associated with larger tumour diameter (chi 2 = 7.490, P = 0.0062) and the presence of clinical metastases (stage IV) (chi 2 = 10.113, P = 0.0015). A non-statistically significant trend of association was observed between p53 mutation, negative oestrogen receptors and lower response rate to therapy. Our results in this group of patients and the heterogeneity of the staining of tumour cells in tissue sections suggest that p53

  5. Techniques and Outcome of Surgery for Locally Advanced and Local Recurrent Rectal Cancer.

    PubMed

    Renehan, A G

    2016-02-01

    Locally advanced primary rectal cancer is variably defined, but generally refers to T3 and T4 tumours. Radical surgery is the mainstay of treatment for these tumours but there is a high-risk for local recurrence. National Institute for Health and Care Excellence (2011) guidelines recommend that patients with these tumours be considered for preoperative chemoradiotherapy and this is the starting point for any discussion, as it is standard care. However, there are many refinements of this pathway and these are the subject of this overview. In surgical terms, there are two broad settings: (i) patients with tumours contained within the mesorectal envelope, or in the lower rectum, limited to invading the sphincter muscles (namely some T2 and most T3 tumours); and (ii) patients with tumours directly invading or adherent to pelvic organs or structures, mainly T4 tumours - here referred to as primary rectal cancer beyond total mesorectal excision (PRC-bTME). Major surgical resection using the principles of TME is the mainstay of treatment for the former. Where anal sphincter sacrifice is indicated for low rectal cancers, variations of abdominoperineal resection - referred to as tailored excision - including the extralevator abdominoperineal excision (ELAPE), are required. There is debate whether or not plastic reconstruction or mesh repair is required after these surgical procedures. To achieve cure in PRC-bTME tumours, most patients require extended multivisceral exenterative surgery, carried out within specialist multidisciplinary centres. The surgical principles governing the treatment of recurrent rectal cancer (RRC) parallel those for PRC-bTME, but typically only half of these patients are suitable for this type of major surgery. Peri-operative morbidity and mortality are considerable after surgery for PRC-bTME and RRC, but unacceptable levels of variation in clinical practice and outcome exist globally. To address this, there are now major efforts to standardise

  6. Prospective Study of Transcatheter Arterial Chemoembolization (TACE) with Ginsenoside Rg3 versus TACE Alone for the Treatment of Patients with Advanced Hepatocellular Carcinoma.

    PubMed

    Zhou, Bo; Yan, Zhiping; Liu, Rong; Shi, Peng; Qian, Sheng; Qu, Xudong; Zhu, Liang; Zhang, Wei; Wang, Jianhua

    2016-08-01

    Purpose To conduct a single-center, open-label, randomized, controlled trial to compare the effectiveness and safety of (a) ginsenoside Rg3 combined with transcatheter arterial chemoembolization (TACE) and (b) TACE alone in patients with advanced hepatocellular carcinoma (HCC). Materials and Methods This trial was approved by the Fudan University Zhongshan Hospital ethics committee and was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC-11001643). After informed consent was obtained, 228 patients with advanced HCC (Barcelona Clinic Liver Cancer stage C) were randomly assigned to receive an Rg3 capsule and undergo TACE (n = 152; mean age ± standard deviation, 52.4 years ± 11.8; 84.2% men) or undergo TACE alone (n = 76; mean age, 52.4 years ± 10.4; 82.9% men). TACE was performed by using iodized oil with epirubicin and gelatin sponge after oxaliplatin and 5-fluorouracil were infused. The primary end point was overall survival. Secondary end points included time to progression, time to untreatable progression, disease control rate, and safety. Data were compared with the log-rank test, and survival curves were generated with the Kaplan-Meier method. Results Median overall survival was 13.2 months (95% confidence interval [CI]: 11.15, 15.26) in the TACE with Rg3 group and 10.1 months (95% CI: 9.14, 11.06) in the control group (hazard ratio, 0.63 [95% CI: 0.46, 0.85]; P = .002). Median time to progression (4.3 vs 3.2 months, respectively; P = .151) and median time to untreatable progression (8.3 vs 7.3 months, respectively; P = .063) were similar in the two groups. Disease control rate was 69.7% in the TACE with Rg3 group versus 51.3% in the control group (P = .012). Constipation and epistaxis were more frequent in the Rg3 with TACE group (P < .05). Importantly, Rg3 alleviated some TACE-related adverse syndromes and blood anomalies. Conclusion In patients with advanced HCC and adequate liver function, the combination of TACE and ginsenoside Rg3 may

  7. Influence of Tumor Thrombus Location on the Outcome of External-beam Radiation Therapy in Advanced Hepatocellular Carcinoma With Macrovascular Invasion

    SciTech Connect

    Hou Jiazhou; Zeng Zhaochong; Zhang Jianying; Fan Jia; Zhou Jian; Zeng Mengsu

    2012-10-01

    Purpose: The present study evaluates the influence of portal vein (PV) vs. inferior vena cava (IVC) tumor thrombosis sites on the effectiveness of external-beam radiation therapy (EBRT) in advanced hepatocellular carcinoma (HCC) with macrovascular invasion. Methods and Materials: We retrospectively reviewed 181 HCC patients with PV and/or IVC tumor thrombi who were referred for EBRT at our institution between 2000 and 2009. EBRT was designed to focus on the tumor thrombi with or without primary intrahepatic tumors to deliver a median total conventional dose of 50 Gy (range, 30-60 Gy). Predictors of survival were identified using univariate and multivariate analyses. Results: The median survival was 10.2, 7.4, 17.4, and 8.5 months for patients with PV branch, PV trunk, IVC, and PV plus IVC tumor thrombosis, respectively. Unfavorable pretreatment predictors were associated by multivariate analysis with lower albumin and higher {alpha}-fetoprotein levels, poorer Child-Pugh liver function classification, multiple intrahepatic foci, lymph node metastases, thrombus location, less chance to receive post-EBRT transarterial chemoembolization (TACE) and the two-dimensional EBRT technique. In comparison to patients with PV tumor thrombosis, patients with IVC thrombi had a higher occurrence of solitary intrahepatic lesions (p = 0.027), well-controlled intrahepatic tumors (p < 0.001), and a better response to EBRT (p < 0.001), and they were more likely to receive post-EBRT TACE (p = 0.033). Conclusions: In HCC, patients with IVC thrombus treated with EBRT had a better response rate and longer survival than those with PV thrombus.

  8. Hepatocellular carcinoma.

    PubMed

    Buendia, Marie-Annick; Neuveut, Christine

    2015-02-01

    The hepatitis B virus (HBV) is a widespread human pathogen that causes liver inflammation, cirrhosis, and hepatocellular carcinoma (HCC). Recent sequencing technologies have refined our knowledge of the genomic landscape and pathogenesis of HCC, but the mechanisms by which HBV exerts its oncogenic role remain controversial. In a prevailing view, inflammation, liver damage, and regeneration may foster the accumulation of genetic and epigenetic defects leading to cancer onset. However, a more direct and specific contribution of the virus is supported by clinical and biological observations. Among genetically heterogeneous HCCs, HBV-related tumors display high genomic instability, which may be attributed to the ability of HBV to integrate its DNA into the host cell genome, provoking chromosomal alterations and insertional mutagenesis of cancer genes. The viral transactivator HBx may also participate in transformation by deregulating diverse cellular machineries. A better understanding of the complex mechanisms linking HBV to HCC will improve prevention and treatment strategies. PMID:25646384

  9. Treatment of Locally Advanced Pancreatic Cancer: The Role of Radiation Therapy

    SciTech Connect

    Johung, Kimberly; Saif, Muhammad Wasif; Chang, Bryan W.

    2012-02-01

    Pancreatic cancer remains associated with an extremely poor prognosis. Surgical resection can be curative, but the majority of patients present with locally advanced or metastatic disease. Treatment for patients with locally advanced disease is controversial. Therapeutic options include systemic therapy alone, concurrent chemoradiation, or induction chemotherapy followed by chemoradiation. We review the evidence to date regarding the treatment of locally advanced pancreatic cancer (LAPC), as well as evolving strategies including the emerging role of targeted therapies. We propose that if radiation is used for patients with LAPC, it should be delivered with concurrent chemotherapy and following a period of induction chemotherapy.

  10. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. Hepatocellular ...

  11. Advanced Algorithms for Local Routing Strategy on Complex Networks.

    PubMed

    Lin, Benchuan; Chen, Bokui; Gao, Yachun; Tse, Chi K; Dong, Chuanfei; Miao, Lixin; Wang, Binghong

    2016-01-01

    Despite the significant improvement on network performance provided by global routing strategies, their applications are still limited to small-scale networks, due to the need for acquiring global information of the network which grows and changes rapidly with time. Local routing strategies, however, need much less local information, though their transmission efficiency and network capacity are much lower than that of global routing strategies. In view of this, three algorithms are proposed and a thorough investigation is conducted in this paper. These algorithms include a node duplication avoidance algorithm, a next-nearest-neighbor algorithm and a restrictive queue length algorithm. After applying them to typical local routing strategies, the critical generation rate of information packets Rc increases by over ten-fold and the average transmission time 〈T〉 decreases by 70-90 percent, both of which are key physical quantities to assess the efficiency of routing strategies on complex networks. More importantly, in comparison with global routing strategies, the improved local routing strategies can yield better network performance under certain circumstances. This is a revolutionary leap for communication networks, because local routing strategy enjoys great superiority over global routing strategy not only in terms of the reduction of computational expense, but also in terms of the flexibility of implementation, especially for large-scale networks. PMID:27434502

  12. Advanced Algorithms for Local Routing Strategy on Complex Networks

    PubMed Central

    Lin, Benchuan; Chen, Bokui; Gao, Yachun; Tse, Chi K.; Dong, Chuanfei; Miao, Lixin; Wang, Binghong

    2016-01-01

    Despite the significant improvement on network performance provided by global routing strategies, their applications are still limited to small-scale networks, due to the need for acquiring global information of the network which grows and changes rapidly with time. Local routing strategies, however, need much less local information, though their transmission efficiency and network capacity are much lower than that of global routing strategies. In view of this, three algorithms are proposed and a thorough investigation is conducted in this paper. These algorithms include a node duplication avoidance algorithm, a next-nearest-neighbor algorithm and a restrictive queue length algorithm. After applying them to typical local routing strategies, the critical generation rate of information packets Rc increases by over ten-fold and the average transmission time 〈T〉 decreases by 70–90 percent, both of which are key physical quantities to assess the efficiency of routing strategies on complex networks. More importantly, in comparison with global routing strategies, the improved local routing strategies can yield better network performance under certain circumstances. This is a revolutionary leap for communication networks, because local routing strategy enjoys great superiority over global routing strategy not only in terms of the reduction of computational expense, but also in terms of the flexibility of implementation, especially for large-scale networks. PMID:27434502

  13. Advanced techniques and armamentarium for dental local anesthesia.

    PubMed

    Clark, Taylor M; Yagiela, John A

    2010-10-01

    Computer-controlled local anesthetic delivery (C-CLAD) devices and systems for intraosseous (IO) injection are important additions to the dental anesthesia armamentarium. C-CLAD using slow infusion rates can significantly reduce the discomfort of local anesthetic infusion, especially in palatal tissues, and facilitate palatal approaches to pulpal nerve block that find special use in cosmetic dentistry, periodontal therapy, and pediatric dentistry. Anesthesia of single teeth can be obtained using either C-CLAD intraligamentary injections or IO injections. Supplementary IO anesthesia is particularly suited for providing effective pain control of teeth diagnosed with irreversible pulpitis. PMID:20831937

  14. Survey of Inmates of Local Jails, 1972. Advance Report.

    ERIC Educational Resources Information Center

    Law Enforcement Assistance Administration (Dept. of Justice), Washington, DC.

    This report contains the major findings from the Survey of Inmates of Local Jails, which was conducted in the summer of 1972 for the Law Enforcement Assistance Administration by the U. S. Bureau of the Census. This first nationwide attempt to assess the socioeconomic characteristics of the country's jail population was a followup to the National…

  15. Treatment of Hepatocellular Carcinoma: A Systematic Review

    PubMed Central

    Lin, Shibo; Hoffmann, Katrin; Schemmer, Peter

    2012-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies, with an increasing incidence. With advances in surgical techniques and instrumentation and the development of molecular-target drugs, a number of potentially curative treatments have become available. Management of HCC patients depends on the stage of their tumor. Liver resection remains the first choice for very early-stage HCC, but it is being challenged by local ablative therapy. For early-stage HCC that meet the Milan criteria, liver transplantation still offers a better outcome; however, local ablative therapy can be a substitute when transplantation is not feasible. Local ablation is also used as a bridging therapy toward liver transplantation. HCC recurrence is the main obstacle to successful treatment, and there is currently no effective means of preventing or treating HCC recurrence. Transarterial therapy is considered suitable for intermediate-stage HCC, while sorafenib is recommended for advanced-stage HCC. This stage-based approach to therapy not only provides acceptable outcomes but also improves the quality of life of HCC patients. Because of the complexity of HCC, therapeutic approaches must be adapted according to the characteristics of each individual patient. This review discusses the current standards and trends in the treatment of HCC. PMID:24159579

  16. [Hepatocellular carcinoma].

    PubMed

    Colombo, Massimo; Sangiovanni, Angelo

    2016-07-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer death and the first in patients with compensated cirrhosis. Chronic infection with hepatitis B and C, alcohol, smoking, exposure to aflatoxin and metabolic syndrome, associated with diabetes and obesity are the main etiological factors. Regardless of etiology, patients with cirrhosis stand as the category at higher risk of developing HCC, and indeed are the target of surveillance programs aimed to the early diagnosis of HCC, the only chance to reduce HCC-related mortality. This notwithstanding, International Scientific Societies have issued recommendations for the management of HCC, a significant number of patients are treated outside guidelines, due to several reasons. Among queries still unsolved, the impact of biological characterization of HCC, along with the biological profiling of patients at risk of developing HCC represent main challenges for the future. Treatment personalization and multimodal treatment being further challenges. This chapter summarizes the recommendations for surveillance, diagnosis and treatment of HCC and focus on future directions. PMID:27571469

  17. Advances in dental local anesthesia techniques and devices: An update

    PubMed Central

    Saxena, Payal; Gupta, Saurabh K.; Newaskar, Vilas; Chandra, Anil

    2013-01-01

    Although local anesthesia remains the backbone of pain control in dentistry, researches are going to seek new and better means of managing the pain. Most of the researches are focused on improvement in the area of anesthetic agents, delivery devices and technique involved. Newer technologies have been developed that can assist the dentist in providing enhanced pain relief with reduced injection pain and fewer adverse effects. This overview will enlighten the practicing dentists regarding newer devices and methods of rendering pain control comparing these with the earlier used ones on the basis of research and clinical studies available. PMID:24163548

  18. Fibrolamellar Hepatocellular Carcinoma: Mechanistic Distinction From Adult Hepatocellular Carcinoma.

    PubMed

    Riggle, Kevin M; Turnham, Rigney; Scott, John D; Yeung, Raymond S; Riehle, Kimberly J

    2016-07-01

    Fibrolamellar hepatocellular carcinoma (FL-HCC) has historically been classified as a rare subtype of HCC. However, unlike "classic" HCC, it occurs in children and young adults without underlying liver disease. The recent discovery of a deletion mutation in all FL-HCCs represented a major advancement in understanding the pathogenesis of this disease. This deletion results in the fusion of the genes encoding a heat shock protein (DNAJB1) and the catalytic subunit of protein kinase A (PKA, PRKACA), and overexpression of PRKACA and enhanced cAMP-dependent PKA activity. This review summarizes recent advancements in FL-HCC pathogenesis and characteristics of the HSP40-PKA C protein. PMID:26990031

  19. Processing advances for localization of beaked whales using time difference of arrival.

    PubMed

    Baggenstoss, Paul M

    2013-06-01

    This paper is concerned with the localization of clicking Blainville's beaked whales (Mesoplodon densirostris) using an array of widely spaced bottom-mounted hydrophones. A set of signal and data processing advances are presented that together make reliable tracking a possibility. These advances include a species-specific detector, elimination of spurious time-difference-of-arrival (TDOA) estimates, improved tracking of TDOA estimates, positive association of TDOA estimates using different hydrophone pairs, and joint localization of multiple whales. A key innovation in three of these advances is the principle of click-matching. The methods are demonstrated using real data. PMID:23742359

  20. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma

    PubMed Central

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-01-01

    Abstract Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches. A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and “en bloc” removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy. The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery. Patients with advanced stage tumors of

  1. Application of advanced reliability methods to local strain fatigue analysis

    NASA Technical Reports Server (NTRS)

    Wu, T. T.; Wirsching, P. H.

    1983-01-01

    When design factors are considered as random variables and the failure condition cannot be expressed by a closed form algebraic inequality, computations of risk (or probability of failure) might become extremely difficult or very inefficient. This study suggests using a simple, and easily constructed, second degree polynomial to approximate the complicated limit state in the neighborhood of the design point; a computer analysis relates the design variables at selected points. Then a fast probability integration technique (i.e., the Rackwitz-Fiessler algorithm) can be used to estimate risk. The capability of the proposed method is demonstrated in an example of a low cycle fatigue problem for which a computer analysis is required to perform local strain analysis to relate the design variables. A comparison of the performance of this method is made with a far more costly Monte Carlo solution. Agreement of the proposed method with Monte Carlo is considered to be good.

  2. Surgery for Locally Advanced T4 Rectal Cancer: Strategies and Techniques.

    PubMed

    Helewa, Ramzi M; Park, Jason

    2016-06-01

    Locally advanced T4 rectal cancer represents a complex clinical condition that requires a well thought-out treatment plan and expertise from multiple specialists. Paramount in the management of patients with locally advanced rectal cancer are accurate preoperative staging, appropriate application of neoadjuvant and adjuvant treatments, and, above all, the provision of high-quality, complete surgical resection in potentially curable cases. Despite the advanced nature of this disease, extended and multivisceral resections with clear margins have been shown to result in good oncological outcomes and offer patients a real chance of cure. In this article, we describe the assessment, classification, and multimodality treatment of primary locally advanced T4 rectal cancer, with a focus on surgical planning, approaches, and outcomes. PMID:27247535

  3. Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer.

    PubMed

    Gollins, S; Sebag-Montefiore, D

    2016-02-01

    Improved surgical technique plus selective preoperative radiotherapy have decreased rectal cancer pelvic local recurrence from, historically, 25% down to about 5-10%. However, this improvement has not reduced distant metastatic relapse, which is the main cause of death and a key issue in rectal cancer management. The current standard is local pelvic treatment (surgery ± preoperative radiotherapy) followed by adjuvant chemotherapy, depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline magnetic resonance imaging, downstaging long-course preoperative chemoradiation (LCPCRT) is generally used. However, for non-CRM-threatened disease, varying approaches are currently adopted in the UK, including straight to surgery, short-course preoperative radiotherapy and LCPCRT. Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating preoperative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full-dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse. Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy-based schedules. Although several measures of neoadjuvant treatment response assessment based on imaging or pathology are promising predictive biomarkers for long-term survival, none has been validated in prospective phase III studies. The phase III setting will enable this, also providing translational opportunities to examine molecular predictors of response and survival. PMID:26645661

  4. Wall conditioning and leak localization in the advanced toroidal facility

    SciTech Connect

    Langley, R.A.; Glowienka, J.C.; Mioduszewski, P.K.; Murakami, M.; Rayburn, T.F.; Simpkins, J.E.; Schwenterly, S.W.; Yarber, J.L.

    1989-01-01

    The Advanced Toroidal Facility (ATF) vacuum vessel and its internal components have been conditioned for plasma operation by baking, discharge cleaning with hydrogen and helium, and gettering with chromium and titanium. The plasma-facing surface of ATF consists mainly of stainless steel with some graphite; the outgassing area is dominated by the graphite because of its open porosity. Since this situation is somewhat different from that in other fusion plasma experiments, in which a single material dominates both the outgassing area and the plasma-facing area, different cleaning and conditioning techniques are required. The situation was aggravated by air leaks in the vacuum vessel, presumably resulting from baking and from vibration during plasma operation. The results of the various cleaning and conditioning techniques used are presented and compared on the basis of residual gas analysis and plasma performance. A technique for detecting leaks from the inside of the vacuum vessel is described; this technique was developed because access to the outside of the vessel is severely restricted by external components. 10 refs., 6 figs., 2 tabs.

  5. Hepatocellular carcinoma.

    PubMed

    Edwards, J T; Macdonald, G A

    2000-05-01

    The incidence of hepatocellular carcinoma (HCC) appears to be declining in Taiwan and potentially in other high-prevalence areas as a consequence of vaccination for hepatitis B virus (HBV). However, there is evidence that the incidence of HCC is increasing in North America and Europe. This appears to be related to the increasing prevalence and duration of hepatitis C virus (HCV) infection in these countries. There is also growing evidence to support an increase in the risk of HCC in patients with HCV who are coinfected with occult HBV (patients who have lost HBV surface antigen but still have detectable HBV DNA either in blood or liver). Occult HBV infection in patients with HCV may be more common than previously thought, and HCC that occurs in this setting appears to have a worse prognosis. There is continuing interest in the effect of interferon therapy on the incidence of HCC in patients with HCV. Several studies from Japan have shown a benefit in patients without cirrhosis, although there are a number of potentially confounding variables that may partly explain these results. Prospective randomized studies are needed to investigate this important question. The molecular biology of HCC and the events of malignant transformation in the liver continue to be areas of intense study. Recently, there has been considerable interest in telomeres, the repeat units on the ends of chromosomes, and the enzyme that maintains these, telomerase. Telomeres shorten with each cell division and can be used to determine the number of divisions a cell has undergone. Eventually they reach a critical length, with further loss resulting in cellular senescence. Telomerase restores telomere length and may help malignant cells escape senescence. Nearly all HCCs have telomerase activity and assessments of telomeres and telomerase may be clinically useful. PMID:17023886

  6. Selection Criteria for the Radical Treatment of Locally Advanced Rectal Cancer

    PubMed Central

    Davies, Mansel Leigh; Harris, Dean; Davies, Mark; Lucas, Malcolm; Drew, Peter; Beynon, John

    2011-01-01

    There are over 14,000 newly diagnosed rectal cancers per year in the United Kingdom of which between 50 and 64 percent are locally advanced (T3/T4) at presentation. Pelvic exenterative surgery was first described by Brunschwig in 1948 for advanced cervical cancer, but early series reported high morbidity and mortality. This approach was later applied to advanced primary rectal carcinomas with contemporary series reporting 5-year survival rates between 32 and 66 percent and to recurrent rectal carcinoma with survival rates of 22–42%. The Swansea Pelvic Oncology Group was established in 1999 and is involved in the assessment and management of advanced pelvic malignancies referred both regionally and UK wide. This paper will set out the selection, assessment, preparation, surgery, and outcomes from pelvic exenterative surgery for locally advanced primary rectal carcinomas. PMID:22312517

  7. Feasibility of intensity-modulated and image-guided radiotherapy for locally advanced esophageal cancer

    PubMed Central

    2014-01-01

    Background In this study the feasibility of intensity-modulated radiotherapy (IMRT) and tomotherapy-based image-guided radiotherapy (IGRT) for locally advanced esophageal cancer was assessed. Methods A retrospective study of ten patients with locally advanced esophageal cancer who underwent concurrent chemotherapy with IMRT (1) and IGRT (9) was conducted. The gross tumor volume was treated to a median dose of 70 Gy (62.4-75 Gy). Results At a median follow-up of 14 months (1-39 months), three patients developed local failures, six patients developed distant metastases, and complications occurred in two patients (1 tracheoesophageal fistula, 1 esophageal stricture requiring repeated dilatations). No patients developed grade 3-4 pneumonitis or cardiac complications. Conclusions IMRT and IGRT may be effective for the treatment of locally advanced esophageal cancer with acceptable complications. PMID:24742268

  8. [A case of an elderly patient having advanced hepatocellular carcinoma with tumor thrombus in the inferior vena cava treated with chemo-radio-therapy--intraarterial infusion of weekly high dose 5-FU (WHF)].

    PubMed

    Yabuuchi, Shinichi; Katayose, Yu; Rikiyama, Toshiki; Oikawa, Masaya; Yamamoto, Kuniharu; Onogawa, Toru; Hayashi, Hiroki; Muto, Mitsuhisa; Unno, Michiaki

    2006-11-01

    The patient was an 81-year-old man, diagnosed with advanced huge hepatocellular carcinoma (HCC) with tumor thrombus extending into the inferior vena cava (Vv3), for which resection was judged impossible. The radio therapy (51 Gy) for tumor thrombus was carried out, and he received a weekly hepatic arterial infusion therapy (weekly high-dose 5-fluorouracil (5-FU)) for these legions. After 8 cycles, the CT scan revealed a minor response of the tumor (SD), and,the tumor marker reduced. After 10 months, these legions had markedly regressed (PR), the tumor thrombus in the inferior vena cava was not detectable. There were no severe side effects. Ten months since the start of chemo-radio therapy, the positron emission tomography (PET) revealed a metastatic tumor of the femoral bone in recurrence. In conclusion, some elderly patients of advanced HCC with tumor thrombus may obtain a long term survival through this treatment. PMID:17212102

  9. Novel therapy for locally advanced triple-negative breast cancer

    PubMed Central

    YAMADA, ATSUKO; OSADA, SHINJI; TANAHASHI, TOSHIYUKI; MATSUI, SATOSHI; SASAKI, YOSHIYUKI; TANAKA, YOSHIHIRO; OKUMURA, NAOKI; MATSUHASHI, NOBUHISA; TAKAHASHI, TAKAO; YAMAGUCHI, KAZUYA; YOSHIDA, KAZUHIRO

    2015-01-01

    To evaluate a novel therapy for triple-negative breast cancer (TNBC), the biological responses to vitamin K3 (VK3) should be considered with the understanding of the features of breast cancer. In human breast cancer cell lines, the effects of VK3 on cell growth inhibition and the cellular signaling pathway were determined by MTT assay and western blotting. In the in vivo study, a subcutaneous tumor model of breast cancer was created, VK3 was injected into the subcutaneous tumors, and tumor size was measured. The IC50 of VK3 for breast cancer cells was calculated to be 11.3–25.1 μM. VK3 induced phosphorylation of whole tyrosine and epidermal growth factor receptor. VK3 mediated phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH2-terminal kinase (JNK) for 30 min. ERK but not JNK phosphorylation was maintained for at least 6 h. In contrast, another antioxidant agent, catalase, showed no effect on either ERK phosphorylation or growth inhibition. On built-up tumors under the skin of mice, local treatment with VK3 was effective in a time- and dose-dependent manner, and the experiments for total tumor volume also showed a dose-dependent effect of VK3. The expression of phosphorylated ERK was clearly detected at 10.9 times the control in tumor tissue, whereas ethanol itself showed no effect. In conclusion, ERK plays a critical role in VK3-induced growth inhibition, and it will be the focus of next steps in the development of molecular therapy for TNBC. PMID:26252842

  10. Radiotherapy for the management of locally advanced squamous cell carcinoma of the head and neck

    PubMed Central

    Ko, Christine; Citrin, Deborah

    2008-01-01

    Background Squamous cell carcinomas of the head and neck (SCCHN) affect approximately 35,000 people in the United States yearly. Although survival has improved with advances in therapy, patients with advanced stages of SCCHN continue to have a poor prognosis. An understanding of rationale for treatment selection, newer developments in therapy, and treatment toxicity is critical. Methods Standard methods of treating locally advanced SCCHN are reviewed. Advances in medical and radiotherapeutic management are discussed and the toxicities of therapy are described. Results Post-operative chemoradiation is used in patients with high risk characteristics. Induction chemotherapy and altered fractionation radiation treatment have been evaluated as alternatives to definitive chemo-radiotherapy. Targeted agents such as cetuximab may prove to increase survival with minimal increase in toxicity profile. Technological improvements such as the use of intensity modulated radiation treatment (IMRT) have proven to decrease some debilitating side effects from radiation treatment. Conclusions Locally advanced SCCHN continues to present a therapeutic challenge. Survival, local control, and quality of life are all goals of treatment. The optimal method of treating locally advanced SCCHN is the subject of ongoing research. Long term side effects can be minimized with the use of newer technologies and with careful treatment planning. PMID:19036056

  11. Stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer

    PubMed Central

    Su, Ting-Shi; Liang, Ping; Lu, Huan-Zhen; Liang, Jian-Ning; Liu, Jian-Min; Zhou, Ying; Gao, Ying-Chuan; Tang, Min-Yang

    2015-01-01

    AIM: To evaluate the efficacy and toxicity of stereotactic body radiotherapy using CyberKnife for locally advanced unresectable and metastatic pancreatic cancer. METHODS: From June 2010 to May 2014, 25 patients with locally advanced unresectable and metastatic pancreatic cancer underwent stereotactic body radiotherapy. Nine patients presented with unresectable locally advanced disease and 16 had metastatic disease. Primary end-points of this study were overall survival, relief of abdominal pain, and toxicity. RESULTS: Fourteen patients were treated with a total dose of 30-36 Gy in three fractions and the remainder with 40-48 Gy in four fractions. Median follow-up was 11 mo (range: 2-25 mo). The median survival duration calculated from the time of stereotactic body radiotherapy for the entire group, the locally advanced group, and the metastatic group was 9.0 mo, 13.5 mo, and 8.5 mo, respectively. Overall survival was 37% and 18% at one and two years, respectively. Abdominal pain relief was achieved within 2 wk of completing radiotherapy in the patients who received successful palliation (13 of 20 patients had significant pain). Five patients (20%) had grade 1 nausea, and one (4%) had grade 2 nausea. No acute grade 3+ toxicity was seen. CONCLUSION: Stereotactic body radiotherapy using the CyberKnife system is a promising, noninvasive, palliative treatment with acceptable toxicity for locally advanced unresectable and metastatic pancreatic cancer. PMID:26185389

  12. Dabrafenib Alone and in Combination With Trametinib Before Surgery in Treating Patients With Locally or Regionally Advanced Melanoma That Can Be Removed By Surgery

    ClinicalTrials.gov

    2013-03-29

    Recurrent Melanoma; Stage IIB Melanoma (Locally Advanced); Stage IIC Melanoma (Locally Advanced); Stage IIIA Melanoma; Stage IIIB Melanoma; Stage IIIC Melanoma; Stage IV Melanoma (Limited, Resectable)

  13. Advances and limits of using population genetics to understand local adaptation.

    PubMed

    Tiffin, Peter; Ross-Ibarra, Jeffrey

    2014-12-01

    Local adaptation shapes species diversity, can be a stepping stone to ecological speciation, and can facilitate species range expansion. Population genetic analyses, which complement organismal approaches in advancing our understanding of local adaptation, have become widespread in recent years. We focus here on using population genetics to address some key questions in local adaptation: what traits are involved? What environmental variables are the most important? Does local adaptation target the same genes in related species? Do loci responsible for local adaptation exhibit trade-offs across environments? After discussing these questions we highlight important limitations to population genetic analyses including challenges with obtaining high-quality data, deciding which loci are targets of selection, and limits to identifying the genetic basis of local adaptation. PMID:25454508

  14. Current status and perspectives of immune-based therapies for hepatocellular carcinoma

    PubMed Central

    Aerts, Maridi; Benteyn, Daphné; Van Vlierberghe, Hans; Thielemans, Kris; Reynaert, Hendrik

    2016-01-01

    Hepatocellular carcinoma (HCC) is a frequent cancer with a high mortality. For early stage cancer there are potentially curative treatments including local ablation, resection and liver transplantation. However, for more advanced stage disease, there is no optimal treatment available. Even in the case of a “curative” treatment, recurrence or development of a new cancer in the precancerous liver is common. Thus, there is an urgent need for novel and effective (adjuvant) therapies to treat HCC and to prevent recurrence after local treatment in patients with HCC. The unique immune response in the liver favors tolerance, which remains a genuine challenge for conventional immunotherapy in patients with HCC. However, even in this “immunotolerant” organ, spontaneous immune responses against tumor antigens have been detected, although they are insufficient to achieve significant tumor death. Local ablation therapy leads to immunogenic tumor cell death by inducing the release of massive amounts of antigens, which enhances spontaneous immune response. New immune therapies such as dendritic cell vaccination and immune checkpoint inhibition are under investigation. Immunotherapy for cancer has made huge progress in the last few years and clinical trials examining the use of immunotherapy to treat hepatocellular carcinoma have shown some success. In this review, we discuss the current status of and offer some perspectives on immunotherapy for hepatocellular carcinoma, which could change disease progression in the near future. PMID:26755874

  15. Treatment of hepatocellular carcinoma: beyond international guidelines.

    PubMed

    Sangiovanni, Angelo; Colombo, Massimo

    2016-01-01

    Treatment of hepatocellular carcinoma (HCC) is guided by the tumour stage. The Barcelona clinical liver cancer (BCLC) score endorsed by the European Society of the Liver EASL divides patients into five prognostic categories, each with a distinct treatment indication. Hepatic resection, orthotopic liver transplantation and percutaneous local ablation are strongly indicated in accurately selected patients with very early (BCLC 0) and early stage (BCLC A) tumours providing a survival rate of between 50 and 75% at year five. In patients with a large tumour burden such as those with intermediate stage BCLC B, repeated treatments with transarterial chemoembolization (TACE) are advocated with clinical benefits (from 16 to 22 months). Survival may also improve in patients who are in poor condition or who do not respond to TACE and those with an advanced HCC (BCLC C), following oral therapy with the multikinase inhibitor, sorafenib. However, most recommendations are based on uncontrolled studies and expert opinions rather than well-designed controlled trials, and up to one-third of patients do not fit recommendations because of advanced age, the presence of significant comorbidities or a strategic location of the nodule. For these patients, treatment of HCC beyond guidelines is often advocated. PMID:26725909

  16. Parenteral Nutrition for Patients Treated for Locally Advanced Inoperable Tumors of the Head and Neck

    ClinicalTrials.gov

    2016-08-10

    Squamous Cell Carcinoma of the Hypopharynx Stage III; Squamous Cell Carcinoma of the Hypopharynx Stage IV; Laryngeal Squamous Cell Carcinoma Stage III; Laryngeal Squamous Cell Carcinoma Stage IV; Oropharyngeal Squamous Cell Carcinoma Stage III; Oropharyngeal Squamous Cell Carcinoma Stage IV; Squamous Cell Carcinoma of the Oral Cavity Stage III; Squamous Cell Carcinoma of the Oral Cavity Stage IV; Locally Advanced Malignant Neoplasm

  17. Quantification of dynamic contrast-enhanced ultrasound in HCC: prediction of response to a new combination therapy of sorafenib and panobinostat in advanced hepatocellular carcinoma.

    PubMed

    Knieling, Ferdinand; Waldner, Maximilian J; Goertz, Ruediger S; Strobel, Deike

    2012-01-01

    Here, we report the case of a patient, who showed an antitumour response to a new combination therapy of sorafenib and the histon deacetylase inhibitor panobinostat (LBH-589). D-CEUS (Dynamic contrast-enhanced ultrasonography) was able to predict response to the new therapy regime and may be an interesting tool in the early evaluation of response to therapy. It might be especially useful to differentiate between responders and non-responders of new-targeted pharmaceuticals like multikinase inhibitors in hepatocellular carcinomas. PMID:23257272

  18. Locally Advanced Lung Cancer: An Optimal Setting for Vaccines and Other Immunotherapies

    PubMed Central

    Iyengar, Puneeth; Gerber, David E.

    2013-01-01

    Lung cancer has traditionally been considered relatively resistant to immunotherapies. However, recent advances in the understanding of tumor-associated antigens, anti-tumor immune responses, and tumor immunosuppression mechanisms have resulted in a number of promising immunomodulatory therapies such as vaccines and checkpoint inhibitors. Locally advanced non-small cell lung cancer (NSCLC) is an optimal setting for these treatments because standard therapies such as surgery, radiation, and chemotherapy may enhance anti-tumor immune effects by debulking the tumor, increasing tumor antigen presentation, and promoting T-cell response and trafficking. Clinical trials incorporating immunomodulatory agents into combined modality therapy of locally advanced NSCLC have shown promising results. Future challenges include identifying biomarkers to predict those patients most likely to benefit from this approach, radiographic assessment of treatment effects, the timing and dosing of combined modality treatment including immunotherapies, and avoidance of potentially overlapping toxicities. PMID:23708072

  19. Oncogenic viruses and hepatocellular carcinoma.

    PubMed

    Ben Ari, Ziv; Weitzman, Ella; Safran, Michal

    2015-05-01

    About 80% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections especially in the setting of established cirrhosis or advanced fibrosis, making HCC prevention a major goal of antiviral therapy. HCC tumors are highly complex and heterogeneous resulting from the aberrant function of multiple molecular pathways. The roles of HCV or HBV in promoting HCC development are still either directly or indirectly are still speculative, but the evidence for both effects is compelling. In patients with chronic hepatitis viral infection, cirrhosis is not a prerequisite for tumorigenesis. PMID:25921667

  20. Yttrium-90 microsphere radioembolization for hepatocellular carcinoma.

    PubMed

    Edeline, Julien; Gilabert, Marine; Garin, Etienne; Boucher, Eveline; Raoul, Jean-Luc

    2015-03-01

    Yttrium-90 (Y90) radioembolization is an emerging strategy to treat liver malignancies, and clinical data supporting its use have accumulated in recent years. Y90-radioembolization has shown clinical effectiveness in intermediate and advanced hepatocellular carcinoma, with a favorable safety profile. Retrospective data show similar levels of effectiveness to transarterial chemoembolization in intermediate hepatocellular carcinoma, with some evidence of better tolerance. While phase 3 studies comparing Y90-radioembolization to chemoembolization in intermediate hepatocellular carcinoma would be difficult to conduct, studies comparing or combining Y90-radioembolization with sorafenib are under way. Questions also remain about the most suitable modalities for defining the dose to administer. Phase 3 studies are under way to clarify the place of Y90-radioembolization in the algorithm of HCC treatment. PMID:26020026

  1. Liver-Directed Radiotherapy for Hepatocellular Carcinoma

    PubMed Central

    Keane, Florence K.; Wo, Jennifer Y.; Zhu, Andrew X.; Hong, Theodore S.

    2016-01-01

    Background The incidence of hepatocellular carcinoma (HCC) continues to increase world-wide. Many patients present with advanced disease with extensive local tumor or vascular invasion and are not candidates for traditionally curative therapies such as orthotopic liver transplantation (OLT) or resection. Radiotherapy (RT) was historically limited by its inability to deliver a tumoricidal dose; however, modern RT techniques have prompted renewed interest in the use of liver-directed RT to treat patients with primary hepatic malignancies. Summary The aim of this review was to discuss the use of external beam RT in the treatment of HCC, with particular focus on the use of stereotactic body radiotherapy (SBRT). We review the intricacies of SBRT treatment planning and delivery. Liver-directed RT involves accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. We also summarize the published data on liver-directed RT, and demonstrate that it is associated with excellent local control and survival rates, particularly in patients who are not candidates for OLT or resection. Key Messages Modern liver-directed RT is safe and effective for the treatment of HCC, particularly in patients who are not candidates for OLT or resection. Liver-directed RT, including SBRT, depends on accurate target identification, precise and reproducible patient immobilization, and assessment of target and organ motion. Further prospective studies are needed to fully delineate the role of liver-directed RT in the treatment of HCC. PMID:27493895

  2. Management of locally advanced carcinoma of the breast by primary radiation therapy

    SciTech Connect

    Harris, J.R.; Sawicka, J.; Gelman, R.; Hellman, S.

    1983-03-01

    A retrospective review of 137 patients with locally advanced breast cancer, but without distant metastases, who were treated with radical radiation therapy is presented. Ninety percent of patients had an initial complete response to their radiation therapy. The 5 year rates of local tumor control, survival free of distant failure, and overall survival were 54% 28% and 30%, respectively. Multivariate analysis revealed that the following features were associated with improved local tumor control: clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. Improved freedom from distant relapse was seen in patients with small primaries and non-inflammatory carcinoma, as well as clinically negative axillary nodes, excisional biopsy, radiation dose greater than 6000 rad, and the use of adjuvant systemic therapy. The results suggest that adequate levels of radiation therapy can provide local tumor control in a significant proportion of patients with locally advanced breast cancer and that adjuvant systemic therapy is useful in improving both local tumor control and freedom from distant relapse in these patients.

  3. Anterior-only Partial Sacrectomy for en bloc Resection of Locally Advanced Rectal Cancer

    PubMed Central

    Roldan, Hector; Perez-Orribo, Luis F.; Plata-Bello, Julio M.; Martin-Malagon, Antonio I.; Garcia-Marin, Victor M.

    2014-01-01

    Study Design Case report. Objective The usual procedure for partial sacrectomies in locally advanced rectal cancer combines a transabdominal and a posterior sacral route. The posterior approach is flawed with a high rate of complications, especially infections and wound-healing problems. Anterior-only approaches have indirectly been mentioned within long series of rectal cancer surgery. We describe a case of partial sacrectomy for en bloc resection of a locally advanced rectal cancer with invasion of the low sacrum through a combined transabdominal and perineal approach without any posterior incision. Methods Through a midline laparotomy, the tumor was dissected and the sacral osteotomy was performed. Once the sacrum was mobile, the muscular attachments to its posterior wall were cut through the perineal approach. This latter route was also used to remove the whole specimen. Results The postoperative period was uneventful in terms of infection and wound healing, but the patient developed right foot dorsiflexion paresis that completely disappeared in 1 month. Resection margins were negative. After a follow-up of 18 months, the patient has no local recurrence but presented lung and liver metastases. Conclusion In cases of rectal cancer involving the low sacrum, the combination of a transabdominal and a perineal route to carry out the partial sacrectomy is a feasible approach that avoids changes of surgical positioning and the morbidity related to posterior incisions. This strategy should be considered when deciding on undertaking partial sacrectomy in locally advanced rectal cancer. PMID:25396109

  4. Immunology of hepatocellular carcinoma

    PubMed Central

    Sachdeva, Meenakshi; Chawla, Yogesh K; Arora, Sunil K

    2015-01-01

    Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can be designed to combat the disease. A dysregulated immune system (including changes in the number and/or function of immune cells, cytokine levels, and the expression of inhibitory receptors or their ligands) plays a key role in the development of HCC. Alterations in either the innate or adaptive arm of the immune system and cross-talk between them make the immune system tolerant to tumors, leading to disease progression. In this review, we have discussed the status and roles of various immune effector cells (e.g., dendritic cells, natural killer cells, macrophages, and T cells), their cytokine profile, and the chemokine-receptor axis in promoting or impeding HCC. PMID:26301050

  5. Association between obesity and local control of advanced rectal cancer after combined surgery and radiotherapy

    PubMed Central

    Choi, Yunseon; Lee, Yun-Han; Park, Sung Kwang; Cho, Heunglae; Ahn, Ki Jung

    2016-01-01

    Purpose: The association between metabolism and cancer has been recently emphasized. This study aimed to find the prognostic significance of obesity in advanced stage rectal cancer patients treated with surgery and radiotherapy (RT). Materials and Methods: We retrospectively reviewed the medical records of 111 patients who were treated with combined surgery and RT for clinical stage 2–3 (T3 or N+) rectal cancer between 2008 and 2014. The prognostic significance of obesity (body mass index [BMI] ≥25 kg/m2) in local control was evaluated. Results: The median follow-up was 31.2 months (range, 4.1 to 85.7 months). Twenty-five patients (22.5%) were classified as obese. Treatment failure occurred in 33 patients (29.7%), including local failures in 13 patients (11.7%), regional lymph node failures in 5, and distant metastases in 24. The 3-year local control, recurrence-free survival, and overall survival rates were 88.7%, 73.6%, and 87.7%, respectively. Obesity (n = 25) significantly reduced the local control rate (p = 0.045; 3-year local control, 76.2%), especially in women (n = 37, p = 0.021). Segregation of local control was best achieved by BMI of 25.6 kg/m2 as a cutoff value. Conclusion: Obese rectal cancer patients showed poor local control after combined surgery and RT. More effective local treatment strategies for obese patients are warranted. PMID:27306771

  6. Radiosensitization of Chemotherapy-Refractory, Locally Advanced or Locally Recurrent Breast Cancer With Trastuzumab: A Phase II Trial

    SciTech Connect

    Horton, Janet K.; Halle, Jan; Ferraro, Madlyn; Carey, Lisa; Moore, Dominic T.; Ollila, David; Sartor, Carolyn I.

    2010-03-15

    Purpose: Trastuzumab (Herceptin), an anti-human epidermal growth factor receptor 2 (HER2) antibody, has been shown to be an effective radiosensitizer in preclinical studies. The present Phase II trial evaluated trastuzumab plus radiotherapy in patients with HER2-positive, chemotherapy-refractory, locally advanced or locoregionally recurrent breast cancer. Methods and Materials: Eligible patients had measurable disease, normal cardiac function, and biopsy-confirmed residual HER2-positive disease. Patients received weekly trastuzumab (2 mg/kg intravenously), concurrent with radiotherapy (50 Gy) to the breast and regional lymph nodes for 5 weeks. If feasible, surgery followed radiotherapy. The primary endpoint was safety, and the secondary endpoint was efficacy (pathologic response and interval to symptomatic local progression). Results: Of the 19 patients enrolled, 7 were ineligible and received radiotherapy alone and 12 received therapy per protocol. Of these 12 patients, 11 had a Stage T4 diagnosis. Grade 3 toxicities included skin (n = 2) and lymphopenia (n = 1). One patient experienced delayed wound healing after surgery. No patients developed symptomatic cardiac dysfunction. Of the 7 patients who had undergone mastectomy, 3 (43%) had a substantial pathologic response (complete response or microscopic residual disease), significantly more than a comparison cohort (2 of 38 or 5%, p = .02). The median interval to symptomatic local progression was not reached. The median overall survival was 39 months. Conclusion: This is the first prospective trial providing evidence for a radiosensitizing effect of trastuzumab in breast cancer. The combination of trastuzumab and radiotherapy was well tolerated.

  7. LOCALIZATION OF SHORT DURATION GRAVITATIONAL-WAVE TRANSIENTS WITH THE EARLY ADVANCED LIGO AND VIRGO DETECTORS

    SciTech Connect

    Essick, Reed; Vitale, Salvatore; Katsavounidis, Erik; Vedovato, Gabriele; Klimenko, Sergey

    2015-02-20

    The Laser Interferometer Gravitational wave Observatory (LIGO) and Virgo advanced ground-based gravitational-wave detectors will begin collecting science data in 2015. With first detections expected to follow, it is important to quantify how well generic gravitational-wave transients can be localized on the sky. This is crucial for correctly identifying electromagnetic counterparts as well as understanding gravitational-wave physics and source populations. We present a study of sky localization capabilities for two search and parameter estimation algorithms: coherent WaveBurst, a constrained likelihood algorithm operating in close to real-time, and LALInferenceBurst, a Markov chain Monte Carlo parameter estimation algorithm developed to recover generic transient signals with latency of a few hours. Furthermore, we focus on the first few years of the advanced detector era, when we expect to only have two (2015) and later three (2016) operational detectors, all below design sensitivity. These detector configurations can produce significantly different sky localizations, which we quantify in detail. We observe a clear improvement in localization of the average detected signal when progressing from two-detector to three-detector networks, as expected. Although localization depends on the waveform morphology, approximately 50% of detected signals would be imaged after observing 100-200 deg{sup 2} in 2015 and 60-110 deg{sup 2} in 2016, although knowledge of the waveform can reduce this to as little as 22 deg{sup 2}. This is the first comprehensive study on sky localization capabilities for generic transients of the early network of advanced LIGO and Virgo detectors, including the early LIGO-only two-detector configuration.

  8. Local institutional development and organizational change for advancing sustainable urban water futures.

    PubMed

    Brown, Rebekah R

    2008-02-01

    This paper presents the local institutional and organizational development insights from a five-year ongoing interdisciplinary research project focused on advancing the implementation of sustainable urban water management. While it is broadly acknowledged that the inertia associated with administrative systems is possibly the most significant obstacle to advancing sustainable urban water management, contemporary research still largely prioritizes investigations at the technological level. This research is explicitly concerned with critically informing the design of methodologies for mobilizing and overcoming the administrative inertia of traditional urban water management practice. The results of fourteen in-depth case studies of local government organizations across Metropolitan Sydney primarily reveal that (i) the political institutionalization of environmental concern and (ii) the commitment to local leadership and organizational learning are key corporate attributes for enabling sustainable management. A typology of five organizational development phases has been proposed as both a heuristic and capacity benchmarking tool for urban water strategists, policy makers, and decision makers that are focused on improving the level of local implementation of sustainable urban water management activity. While this investigation has focused on local government, these findings do provide guideposts for assessing the development needs of future capacity building programs across a range of different institutional contexts. PMID:18027015

  9. Local Institutional Development and Organizational Change for Advancing Sustainable Urban Water Futures

    NASA Astrophysics Data System (ADS)

    Brown, Rebekah R.

    2008-02-01

    This paper presents the local institutional and organizational development insights from a five-year ongoing interdisciplinary research project focused on advancing the implementation of sustainable urban water management. While it is broadly acknowledged that the inertia associated with administrative systems is possibly the most significant obstacle to advancing sustainable urban water management, contemporary research still largely prioritizes investigations at the technological level. This research is explicitly concerned with critically informing the design of methodologies for mobilizing and overcoming the administrative inertia of traditional urban water management practice. The results of fourteen in-depth case studies of local government organizations across Metropolitan Sydney primarily reveal that (i) the political institutionalization of environmental concern and (ii) the commitment to local leadership and organizational learning are key corporate attributes for enabling sustainable management. A typology of five organizational development phases has been proposed as both a heuristic and capacity benchmarking tool for urban water strategists, policy makers, and decision makers that are focused on improving the level of local implementation of sustainable urban water management activity. While this investigation has focused on local government, these findings do provide guideposts for assessing the development needs of future capacity building programs across a range of different institutional contexts.

  10. [Role of induction chemo- and radiotherapy in the treatment of locally advance breast cancer].

    PubMed

    Voznyĭ, E K; Kharchenko, V P; Pan'shin, G A; Gurov, S N; Dobrovol'skaia, N I; Galil-Ogly, G A; Khmelevskiĭ, E V; Alipchenko, L A; Bol'shakova, S A

    2000-01-01

    336 patients with locally-advanced breast cancer underwent neoadjuvant chemotherapy or chemoradiotherapy. Increase in T- and N-indices (change of stage after neoadjuvant chemotherapy) proved an important prognostic factor. Survival rates correlated with clinical effect and dropped as it diminished. This tendency was clear in both groups. There was no relationship between stage and overall and disease-free survival rates at early stages but later they declined as T- and N-indices decreased. PMID:11219950

  11. Chemoembolization for hepatocellular carcinoma.

    PubMed

    Lencioni, Riccardo

    2012-08-01

    Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with preserved liver function and asymptomatic, noninvasive multinodular hepatocellular carcinoma (HCC) confined to the liver. However, the survival benefit of conventional TACE-including the administration of an anticancer agent-in-oil emulsion followed by embolic agents-reported in randomized controlled trials and meta-analyses was described as modest. Various strategies to improve outcomes for this patient group have become the subject of much ongoing clinical research. The introduction of embolic, drug-eluting beads (DEB) for transarterial administration has been shown to significantly reduce liver toxicity and systemic drug exposure compared to conventional regimens. The addition of molecular targeted drugs to the therapeutic armamentarium for HCC has prompted the design of clinical trials aimed at investigating the synergies between TACE and systemic treatments. Combining TACE with agents with anti-angiogenic properties represents a promising strategy, because TACE is thought to cause local hypoxia, resulting in a temporary increase in levels of vascular endothelial growth factor. Recently, a large phase II randomized, double-blind, placebo-controlled trial (the SPACE study) has shown that the concurrent administration of DEB-TACE and sorafenib has a manageable safety profile and has suggested that time to progression and time to vascular invasion or extrahepatic spread may be improved with respect to DEB-TACE alone. These data support the further evaluation of molecular targeted, systemically active agents in combination with DEB-TACE in a phase III setting. PMID:22846867

  12. 6.3 MeV fast neutrons in the treatment of patients with locally advanced and locally recurrent breast cancer

    NASA Astrophysics Data System (ADS)

    Velikaya, V. V.; Musabaeva, L. I.; Lisin, V. A.; Startseva, Zh. A.

    2016-08-01

    The study included 135 breast cancer patients (70 patients with locally recurrent breast cancer and 65 patients with locally advanced breast cancer with unfavorable prognostic factors) who received the neutron therapy alone or in combination with the photon therapy. The neutron therapy was shown to be effective in multimodality treatment of patients with locally advanced and locally recurrent breast cancer. The 8-year survival rate in patients without repeated breast cancer recurrence was 87.6 ± 8.7% after the neutron and neutron-photon therapy and 54.3 ± 9.2% after the electron beam therapy.

  13. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  14. Management of locally advanced and metastatic colon cancer in elderly patients

    PubMed Central

    Kurniali, Peter C; Hrinczenko, Borys; Al-Janadi, Anas

    2014-01-01

    Colon cancer is the second leading cause of cancer mortality in the United States with a median age at diagnosis of 69 years. Sixty percent are diagnosed over the age of 65 years and 36% are 75 years or older. At diagnosis, approximately 58% of patients will have locally advanced and metastatic disease, for which systemic chemotherapy has been shown to improve survival. Treatment of cancer in elderly patients is more challenging due to multiple factors, including disabling co-morbidities as well as a decline in organ function. Cancer treatment of elderly patients is often associated with more toxicities that may lead to frequent hospitalizations. In locally advanced disease, fewer older patients receive adjuvant chemotherapy despite survival benefit and similar toxicity when compared to their younger counterparts. A survival benefit is also observed in the palliative chemotherapy setting for elderly patients with metastatic disease. When treating elderly patients with colon cancer, one has to consider drug pharmacokinetics and pharmacodynamics. Since chronological age is a poor marker of a patient’s functional status, several methods of functional assessment including performance status and activities of daily living (ADL) or instrumental ADL, or even a comprehensive geriatric assessment, may be used. There is no ideal chemotherapy regimen that fits all elderly patients and so a regimen needs to be tailored for each individual. Important considerations when treating elderly patients include convenience and tolerability. This review will discuss approaches to the management of elderly patients with locally advanced and metastatic colon cancer. PMID:24616568

  15. Liver cancer - hepatocellular carcinoma

    MedlinePlus

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or older. ...

  16. [A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

    PubMed

    Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

    2014-01-01

    Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis. PMID:23092693

  17. [Combination Chemotherapy Using Sorafenib and Hepatic Arterial Infusion with a Fine-Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis--A Case Report].

    PubMed

    Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Murata, Akihiro; Sakae, Masayuki; Kurihara, Shigeaki; Tashima, Tetsuzo; Deguchi, Sota; Nakai, Takashi; Kawasaki, Yasuko; Kioka, Kiyohide

    2015-11-01

    Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor-shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call®). A 57-year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call® was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call® has been performed once for 6 weeks. After performing HAIC with IA-call® 5 times, the serum levels of HCC tumor markers AFP and PIVKA-Ⅱdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease. PMID:26805203

  18. Advanced age decreases local calcium signaling in endothelium of mouse mesenteric arteries in vivo.

    PubMed

    Boerman, Erika M; Everhart, Jesse E; Segal, Steven S

    2016-05-01

    Aging is associated with vascular dysfunction that impairs tissue perfusion, physical activity, and the quality of life. Calcium signaling in endothelial cells (ECs) is integral to vasomotor control, exemplified by localized Ca(2+) signals within EC projections through holes in the internal elastic lamina (IEL). Within these microdomains, endothelium-derived hyperpolarization is integral to smooth muscle cell (SMC) relaxation via coupling through myoendothelial gap junctions. However, the effects of aging on local EC Ca(2+) signals (and thereby signaling between ECs and SMCs) remain unclear, and these events have not been investigated in vivo. Furthermore, it is unknown whether aging affects either the number or the size of IEL holes. In the present study, we tested the hypothesis that local EC Ca(2+) signaling is impaired with advanced age along with a reduction in IEL holes. In anesthetized mice expressing a Ca(2+)-sensitive fluorescent protein (GCaMP2) selectively in ECs, our findings illustrate that for mesenteric arteries controlling splanchnic blood flow the frequency of spontaneous local Ca(2+) signals in ECs was reduced by ∼85% in old (24-26 mo) vs. young (3-6 mo) animals. At the same time, the number (and total area) of holes per square millimeter of IEL was reduced by ∼40%. We suggest that diminished signaling between ECs and SMCs contributes to dysfunction of resistance arteries with advanced age.Listen to this article's corresponding podcast at http://ajpheart.podbean.com/e/aging-impairs-endothelial-ca2-signaling/. PMID:26945073

  19. [The impact of the VAC-treatment for locally advanced malignancy of the scalp].

    PubMed

    Schintler, M V; Prandl, E-C; Wittguber, G; Zink, B; Spendel, S; Hellbom, B; Scharnagl, E

    2004-05-01

    Locally advanced cutaneous malignancy of the scalp is a disease that requires an aggressive approach to resection and reconstruction. In cases where the pericranium is intact a split-thickness skin graft is a simple treatment, since direct closure often fails because due to the lack of elasticity of the scalp. If there is a loss of periosteum or a skull defect local or free flaps are necessary for sufficient coverage. Increasing geriatric and polymorbid patients with impaired wound healing require surgical treatment, considering pros and cons for general anaesthesia. A simple method of both, combining radicality of tumor resection with outer table bone and skin grafting as a two stage procedure, while minimizing perioperative risk using local anaesthesia and analgo-sedation, using the vacuum assisted closure device, is presented. PMID:15168314

  20. Hepatocellular carcinoma: clinical frontiers and perspectives

    PubMed Central

    Bruix, Jordi; Gores, Gregory J; Mazzaferro, Vincenzo

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death and is currently the main event leading to death in patients with cirrhosis. Evolving information suggests that the metabolic syndrome with non-alcoholic liver disease may be an important cause of HCC in addition to viral hepatitis and alcohol-induced liver disease. The molecular pathogenesis is extremely complex and heterogeneous. To date the molecular information has not impacted on treatment decisions. Periodic surveillance imaging of patients with cirrhosis is widely practiced, especially because diagnostic, radiographic criteria for early-stage HCC have been defined (including nodules between 1 and 2 cm) and effective treatment is available for tumours detected at an early stage. Worldwide the approach to resection versus transplantation varies depending upon local resources, expertise and donor availability. The criteria for transplantation are discussed, and the controversial areas highlighted with evidence-based recommendations provided. Several approaches are available for intermediate stage disease, including radiofrequency ablation, transarterial chemoembolisation and radioembolisation; the rationale for these therapies is buttressed by appropriate outcome-based studies. For advanced disease, systemic therapy with sorafenib remains the option best supported by current data. Thus, while several trials have failed to improve the benefits of established therapies, studies assessing the sequential or combined application of those already known to be beneficial are needed. Also, new concepts are provided in regards to selecting and stratifying patients for second-line studies, which may help explain the failure of prior studies. PMID:24531850

  1. Neoadjuvant Radiotherapy/Chemoradiotherapy in Locally Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Yalman, Deniz

    2015-01-01

    Locally advanced non-small cell lung cancer (NSCLC) consists of a heterogeneous group of patients, and the optimal treatment is still controversial. The current standard of care is concurrent chemoradiotherapy. The prognosis is still poor, with high rates of local and distant failure despite multimodality treatment. One of the efforts to improve outcomes in these patients is to use neoadjuvant treatment to improve resectability, and downstaging the nodal disease, which has a clear impact on prognosis. Radiotherapy as the sole neoadjuvant modality has been used historically without any survival benefit, but with increased toxicity. After the demonstrating a survival benefit by combining radiotherapy and chemotherapy, phase II studies were started to determine the neoadjuvant administration of these two modalities together. Although the results of these studies revealed a heterogeneous postinduction pathologic complete response, tumor and nodal down-staging can be achieved at the cost of a slightly higher morbidity and mortality. Subsequent phase III trials also failed to show a survival benefit to surgery, but indicated that there may be a subset of patients with locally advanced disease who can benefit from resection unless pneumonectomy is not provided. In order to increase the efficacy of radiotherapy, hyperfractionated-accelerated schedules have been used with promising complete pathologic response rates, which might improve prognosis. Recently, studies applying high radiotherapy doses in the neoadjuvant setting demonstrated the safety of resection after radiotherapy, with high nodal clearance rates and encouraging long-term survival results. In conclusion, neoadjuvant treatment of locally advanced NSCLC is one of the most challenging issues in the treatment of this disease, but it can be offered to appropriately selected patients, and should be done by a multidisciplinary team. Individual risk profiles, definite role of radiotherapy with optimal timing, and

  2. The role of palliative radiation therapy in symptomatic locally advanced gastric cancer

    SciTech Connect

    Tey, Jeremy . E-mail: Jeremy_Tey@mail.nhg.com.sg; Back, Michael F.; Shakespeare, Thomas P.; Mukherjee, Rahul K.; Lu, Jiade J.; Lee, Khai Mun; Wong, Lea Choung; Leong, Cheng Nang; Zhu Ming

    2007-02-01

    Purpose: To review the outcome of palliative radiotherapy (RT) alone in patients with symptomatic locally advanced or recurrent gastric cancer. Methods and Materials: Patients with symptomatic locally advanced or recurrent gastric cancer who were managed palliatively with RT at Cancer Institute, Singapore were retrospectively reviewed. Study end points included symptom response, median survival, and treatment toxicity (retrospectively scored using the Common Toxicity Criteria v3.0 [CTC]). Results: Between November 1999 and December 2004, 33 patients with locally advanced or recurrent gastric cancer were managed with palliative intent using RT alone. Median age was 76 years (range, 38-90 years). Twenty-one (64%) patients had known distant metastatic disease at time of treatment. Key index symptoms were bleeding (24 patients), obstruction (8 patients), and pain (8 patients). The majority of patients received 30 Gy/10 fractions (17 patients). Dose fractionation regimen ranged from an 8-Gy single fraction to 40 Gy in 16 fractions. Median survival was 145 days, actuarial 12-month survival 8%. A total of 54.3% of patients (13/24) with bleeding responded (median duration of response of 140 days), 25% of patients (2/8) with obstruction responded (median duration of response of 102 days), and 25% of patients (2/8) with pain responded (median duration of response of 105 days). No obvious dose-response was evident. One Grade 3 CTC equivalent toxicity was recorded. Conclusion: External beam RT alone is an effective and well tolerated modality in the local palliation of gastric cancer, with palliation lasting the majority of patients' lives.

  3. Interstitial high-dose-rate brachytherapy in locally advanced and recurrent vulvar cancer

    PubMed Central

    Białas, Brygida; Fijałkowski, Marek; Wojcieszek, Piotr; Szlag, Marta; Cholewka, Agnieszka; Ślęczka, Maciej; Kołosza, Zofia

    2016-01-01

    Purpose The aim of the study was to report our experience with high-dose-rate interstitial brachytherapy (HDR-ISBT) in locally advanced and recurrent vulvar cancer. Material and methods Between 2004 and 2014, fourteen women with locally advanced or recurrent vulvar cancer were treated using HDR-ISBT in our Centre. High-dose-rate interstitial brachytherapy was performed as a separate treatment or in combination with external beam radiotherapy (EBRT) (given prior to brachytherapy). Results Patients were divided into: group I (n = 6) with locally advanced tumors, stages III-IVA after an incisional biopsy only, and group II (n = 8) with recurrent vulvar cancer after previous radical surgery. In group I, median follow up was 12 months (range 7-18 months); 1-year overall survival (OS) was 83%. Transient arrest of cancer growth or tumor regression was noticed in all patients but 4/6 developed relapse. Median time to failure was 6.3 months (range 3-11 months). The 1-year progression-free survival (PFS) was 33%. In group II, median follow up was 28 months (range 13-90 months). The 1-year and 3-year OS was 100% and 80%, respectively. The arrest of cancer growth or tumor regression was achieved in all patients. In 4/8 patients neither clinical nor histological symptoms of relapse were observed but 4/8 women experienced relapse. Median time to failure was 31 months (range 13-76 months). The 1-year and 3-year PFS was 100% and 62.5%, respectively. Two patients (14.3%) in group II had severe late toxicity (G3). Conclusions High-dose-rate interstitial brachytherapy is a well-tolerated treatment option in selected patients with advanced or recurrent vulvar cancer. It is a safe and effective treatment modality for advanced and recurrent vulvar cancer, yielding good local control with acceptable late treatment related side effects. In our study, patients with recurrent vulvar cancer had better results in HDR-ISBT treatment, probably because of the smaller tumor volume. This

  4. Multimodality approach to surgical management of locally advanced epidermoid carcinoma of the anorectum

    SciTech Connect

    Wanebo, H.J.; Futrell, W.; Constable, W.

    1981-06-15

    Seven patients (five female, two male) had locally advanced epidermoid carcinoma of the anal canal. Three patients had recurrent or persistent disease previously treated and four had advanced primary cancer. Five patients had groin node metastasis. The treatment protocol consisted of chemotherapy with continuous 5-day infusion of 5-fluorouracil, 750 mg/m2, and mitomycin C, 15 mg/m2, by bolus injection and radiation 3000 rads. All patients received one or two cycles of chemotherapy pre-operatively and four (not previously irradiated) received radiation. Tumor regression greater than 50% occurred in five patients, minor regression (25-50%) occurred in one patient and one patient showed no regression (on chemotherapy alone). All patients had total resection of all gross tumor with microscopic clear margins and five had groin dissection. One patient had no residual cancer in specimen and one patient had a microscopic focus only. Four of five patients had residual nodal metastases at groin dissection. Currently three patients are free of disease at 24, 24, and 26 months. Two patients died with disease at 6 months and 34 months, and two patients died of other causes while still free of disease, at 4 and 5 months after resection. Multimodality therapy of locally advanced epidermoid cancer of anal canal can provide effective control and palliation of many of these tumors and, in some, possibly effect cure.

  5. Cediranib (AZD2171) in Patients with Advanced Hepatocellular Carcinoma: A Phase II North Central Cancer Treatment Group (NCCTG) Clinical Trial1

    PubMed Central

    Alberts, Steven R.; Fitch, Tom R.; Kim, George P.; Morlan, Bruce W.; Dakhil, Shaker R.; Gross, Howard M.; Nair, Suresh

    2011-01-01

    Objectives Vascular endothelial growth factor (VEGF) has been shown to be overexpressed in several studies of hepatocellular carcinoma (HCC). Cediranib is a potent inhibitor of VEGF signaling. We assessed the efficacy and toxicity of cediranib in patients with HCC. Methods Twenty-eight patients with unresectable or metastatic HCC were enrolled on this study. Patients received 45 mg of cediranib orally, once daily, for 28 day cycles. The primary objective of this Phase II study was to assess six-month survival. Secondary objectives were to assess tumor response, time-to-progression, and toxicity. Results All 28 patients were evaluable for efficacy outcomes. Twelve patients (42.9%) survived 6 months, 15 (53.6%) died within 6 months, and one (3.6%) was lost to follow-up before 6 months. The median overall survival was 5.8 months (95% CI: 3.4–7.3 months). No patients experienced confirmed response. The median time-to-progression was 2.8 months (95% CI: 2.3 – 4.4 months). Twenty-six patients (93%) experienced a grade 3+ adverse event (AE) with the most common AEs being fatigue (46%), anorexia (25%), hypertension (21%), and elevated alanine aminotransferase (ALT) (18%). Conclusions Due to toxicity, cediranib at this dose and schedule is not an effective treatment in patients with unresectable or metastatic HCC. PMID:21422991

  6. Induction Gemcitabine and Stereotactic Body Radiotherapy for Locally Advanced Nonmetastatic Pancreas Cancer

    SciTech Connect

    Mahadevan, Anand; Miksad, Rebecca; Goldstein, Michael; Sullivan, Ryan; Bullock, Andrea; Buchbinder, Elizabeth; Pleskow, Douglas; Sawhney, Mandeep; Kent, Tara; Vollmer, Charles; Callery, Mark

    2011-11-15

    Purpose: Stereotactic body radiotherapy (SBRT) has been used successfully to treat patients with locally advanced pancreas cancer. However, many patients develop metastatic disease soon after diagnosis and may receive little benefit from such therapy. We therefore retrospectively analyzed a planned strategy of initial chemotherapy with restaging and then treatment for those patients with no evidence of metastatic progression with SBRT. Methods and Materials: Forty-seven patients received gemcitabine (1,000 mg/m{sup 2} per week for 3 weeks then 1 week off) until tolerance, at least six cycles, or progression. Patients without metastases after two cycles were treated with SBRT (tolerance-based dose of 24-36 Gy in 3 fractions) between the third and fourth cycles without interrupting the chemotherapy cycles. Results: Eight of the 47 patients (17%) were found to have metastatic disease after two cycles of gemcitabine; the remaining 39 patients received SBRT. The median follow-up for survivors was 21 months (range, 6-36 months). The median overall survival for all patients who received SBRT was 20 months, and the median progression-free survival was 15 months. The local control rate was 85% (33 of 39 patients); and 54% of patients (21 of 39) developed metastases. Late Grade III toxicities such as GI bleeding and obstruction were observed in 9% (3/39) of patients. Conclusion: For patients with locally advanced pancreas cancer, this strategy uses local therapy for those who are most likely to benefit from it and spares those patients with early metastatic progression from treatment. SBRT delivers such local therapy safely with minimal interruption to systemic chemotherapy, thereby potentially improving the outcome in these patients.

  7. Gemcitabine Chemotherapy and Single-Fraction Stereotactic Body Radiotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Schellenberg, Devin; Goodman, Karyn A.; Lee, Florence; Chang, Stephanie; Kuo, Timothy; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Greco, Ralph; Yang, George P.; Koong, Albert C.

    2008-11-01

    Purpose: Fractionated radiotherapy and chemotherapy for locally advanced pancreatic cancer achieves only modest local control. This prospective trial evaluated the efficacy of a single fraction of 25 Gy stereotactic body radiotherapy (SBRT) delivered between Cycle 1 and 2 of gemcitabine chemotherapy. Methods and Materials: A total of 16 patients with locally advanced, nonmetastatic, pancreatic adenocarcinoma received gemcitabine with SBRT delivered 2 weeks after completion of the first cycle. Gemcitabine was resumed 2 weeks after SBRT and was continued until progression or dose-limiting toxicity. The gross tumor volume, with a 2-3-mm margin, was treated in a single 25-Gy fraction by Cyberknife. Patients were evaluated at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All 16 patients completed SBRT. A median of four cycles (range one to nine) of chemotherapy was delivered. Three patients (19%) developed local disease progression at 14, 16, and 21 months after SBRT. The median survival was 11.4 months, with 50% of patients alive at 1 year. Patients with normal carbohydrate antigen (CA)19-9 levels either at diagnosis or after Cyberknife SBRT had longer survival (p <0.01). Acute gastrointestinal toxicity was mild, with 2 cases of Grade 2 (13%) and 1 of Grade 3 (6%) toxicity. Late gastrointestinal toxicity was more common, with five ulcers (Grade 2), one duodenal stenosis (Grade 3), and one duodenal perforation (Grade 4). A trend toward increased duodenal volumes radiated was observed in those experiencing late effects (p = 0.13). Conclusion: SBRT with gemcitabine resulted in comparable survival to conventional chemoradiotherapy and good local control. However, the rate of duodenal ulcer development was significant.

  8. Application of Laparoscopic Extralevator Abdominoperineal Excision in Locally Advanced Low Rectal Cancer

    PubMed Central

    Wang, Yan-Lei; Dai, Yong; Jiang, Jin-Bo; Yuan, Hui-Yang; Hu, San-Yuan

    2015-01-01

    Background: When compared with conventional abdominoperineal resection (APR), extralevator abdominoperineal excision (ELAPE) has been demonstrated to reduce the risk of local recurrence for the treatment of locally advanced low rectal cancer. Combined with the laparoscopic technique, laparoscopic ELAPE (LELAPE) has the potential to reduce invasion and hasten postoperative recovery. In this study, we aim to investigate the advantages of LELAPE in comparison with conventional APR. Methods: From October 2010 to February 2013, 23 patients with low rectal cancer (T3–4N0–2M0) underwent LELAPE; while during the same period, 25 patients were treated with conventional APR. The patient characteristics, intraoperative data, postoperative complications, and follow-up results were retrospectively compared and analyzed. Results: The basic patient characteristics were similar; but the total operative time for the LELAPE was longer than that of the conventional APR group (P = 0.014). However, the operative time for the perineal portion was comparable between the two groups (P = 0.328). The LELAPE group had less intraoperative blood loss (P = 0.022), a lower bowel perforation rate (P = 0.023), and a positive circumferential margin (P = 0.028). Moreover, the patients, who received the LELAPE, had a lower postoperative Visual Analog Scale, quicker recovery of bowel function (P = 0.001), and a shorter hospital stay (P = 0.047). However, patients in the LELAPE group suffered more chronic perineal pain (P = 0.002), which may be related to the coccygectomy (P = 0.033). Although the metastasis rate and mortality rate were similar between the two groups, the local recurrence rate of the LELAPE group was statistically improved (P = 0.047). Conclusions: When compared with conventional APR, LELAPE has the potential to reduce the risk of local recurrence, and decreases operative invasion for the treatment of locally advanced low rectal cancer. PMID:25963355

  9. Chemoembolization and Radioembolization for Hepatocellular Carcinoma

    PubMed Central

    Salem, Riad; Lewandowski, Robert J.

    2013-01-01

    Hepatocellular carcinoma (HCC) continues to represent a major worldwide problem. While treatments such as resection, transplantation and ablation may provide a chance for cure, these options are often precluded because of advanced disease presentation. Palliative treatments include transarterial embolization and systemic therapies. This review will summarize the state of the science for embolic therapies in HCC (conventional and drug-eluting chemoembolization, radioembolization), as well as discuss related topics including HCC staging, assessment of response and ongoing clinical trials. PMID:23357493

  10. Paclitaxel and cisplatin with concurrent radiotherapy followed by surgery in locally advanced thymic carcinoma.

    PubMed

    Fukuda, Minoru; Obase, Yasushi; Miyashita, Naoyuki; Kobashi, Yoshihiro; Mohri, Keiji; Ueno, Shiro; Hayama, Makio; Shimizu, Katsuhiko; Nishimura, Hironori; Nakata, Masao; Oka, Mikio

    2007-01-01

    Thymic carcinoma is a rare neoplasm with a poor prognosis. We report the clinical course of a patient who received complete surgical resection after effective induction treatment. A 72-year-old woman with advanced thymic carcinoma (squamous cell carcinoma, stage IVb) was considered as nonresectable due to invasion of neighboring organs and mediastinal lymph node metastasis. Two cycles of chemotherapy, consisting of paclitaxel (180 mg/m2) plus cisplatin (80 mg/m2), combined with thoracic radiotherapy (total 54 Gy) were performed concurrently and complete radical resection could then be performed. She is currently alive and ambulatory and has remained disease-free for two years. This multimodal treatment may be a good treatment option for locally advanced thymic carcinoma. PMID:17595782

  11. Percutaneous irreversible electroporation of locally advanced pancreatic carcinoma using the dorsal approach: a case report.

    PubMed

    Scheffer, Hester J; Melenhorst, Marleen C A M; Vogel, Jantien A; van Tilborg, Aukje A J M; Nielsen, Karin; Kazemier, Geert; Meijerink, Martijn R

    2015-06-01

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively. PMID:25288173

  12. Results of fast neutron teletherapy for locally advanced head and neck tumors

    SciTech Connect

    Battermann, J.J.; Breur, K.

    1981-08-01

    An analysis is given of the results of fast neutron therapy for locally advanced tumors of the head and neck region. All patients were treated five times per week with a 14 MeV d + T neutron beam and received dosages of about 19 Gy/sub nadvanced tumors were treated in this pilot study, the survival time is rather short for most patients. Only 8 patients are alive at the time of writing. The results of treatment for inoperable malignancies of the major salivary glands are very promising, as initial complete regression was achieved in over 90% (12/13).

  13. Percutaneous Irreversible Electroporation of Locally Advanced Pancreatic Carcinoma Using the Dorsal Approach: A Case Report

    SciTech Connect

    Scheffer, Hester J. Melenhorst, Marleen C. A. M.; Vogel, Jantien A.; Tilborg, Aukje A. J. M. van; Nielsen, Karin Kazemier, Geert; Meijerink, Martijn R.

    2015-06-15

    Irreversible electroporation (IRE) is a novel image-guided ablation technique that is increasingly used to treat locally advanced pancreatic carcinoma (LAPC). We describe a 67-year-old male patient with a 5 cm stage III pancreatic tumor who was referred for IRE. Because the ventral approach for electrode placement was considered dangerous due to vicinity of the tumor to collateral vessels and duodenum, the dorsal approach was chosen. Under CT-guidance, six electrodes were advanced in the tumor, approaching paravertebrally alongside the aorta and inferior vena cava. Ablation was performed without complications. This case describes that when ventral electrode placement for pancreatic IRE is impaired, the dorsal approach could be considered alternatively.

  14. Disparities in the Use of Radiation Therapy in Patients With Local-Regionally Advanced Breast Cancer

    SciTech Connect

    Martinez, Steve R.; Beal, Shannon H.; Chen, Steven L.; Canter, Robert J.; Khatri, Vijay P.; Chen, Allen; Bold, Richard J.

    2010-11-01

    Background: Radiation therapy (RT) is indicated for the treatment of local-regionally advanced breast cancer (BCa). Hypothesis: We hypothesized that black and Hispanic patients with local-regionally advanced BCa would receive lower rates of RT than their white counterparts. Methods: The Surveillance Epidemiology and End Results database was used to identify white, black, Hispanic, and Asian patients with invasive BCa and {>=}10 metastatic lymph nodes diagnosed between 1988 and 2005. Univariate and multivariate logistic regression evaluated the relationship of race/ethnicity with use of RT. Multivariate models stratified for those undergoing mastectomy or lumpectomy. Results: Entry criteria were met by 12,653 patients. Approximately half of the patients did not receive RT. Most patients were white (72%); the remainder were Hispanic (10.4%), black (10.3%), and Asian (7.3%). On univariate analysis, Hispanics (odd ratio [OR] 0.89; 95% confidence interval [CI], 0.79-1.00) and blacks (OR 0.79; 95% CI, 0.70-0.89) were less likely to receive RT than whites. On multivariate analysis, blacks (OR 0.76; 95% CI, 0.67-0.86) and Hispanics (OR 0.80; 95% CI, 0.70-0.90) were less likely than whites to receive RT. Disparities persisted for blacks (OR 0.74; 95% CI, 0.64-0.85) and Hispanics (OR 0.77; 95% CI, 0.67-0.89) who received mastectomy, but not for those who received lumpectomy. Conclusions: Many patients with local-regionally advanced BCa do not receive RT. Blacks and Hispanics were less likely than whites to receive RT. This disparity was noted predominately in patients who received mastectomy. Future efforts at improving rates of RT are warranted. Efforts at eliminating racial/ethnic disparities should focus on black and Hispanic candidates for postmastectomy RT.

  15. Effectiveness of Androgen-Deprivation Therapy and Radiotherapy for Older Men With Locally Advanced Prostate Cancer

    PubMed Central

    Bekelman, Justin E.; Mitra, Nandita; Handorf, Elizabeth A.; Uzzo, Robert G.; Hahn, Stephen A.; Polsky, Daniel; Armstrong, Katrina

    2015-01-01

    Purpose We examined whether the survival advantage of androgen-deprivation therapy with radiotherapy (ADT plus RT) relative to ADT alone for men with locally advanced prostate cancer reported in two randomized trials holds in real-world clinical practice and extended the evidence to patients poorly represented in the trials. Methods We conducted nonrandomized effectiveness studies of ADT plus RT versus ADT in three groups of patients diagnosed between 1995 and 2007 and observed through 2009 in the SEER-Medicare data set: (1) the randomized clinical trial (RCT) cohort, which included men age 65 to 75 years and was most consistent with participants in the randomized trials; (2) the elderly cohort, which included men age > 75 years with locally advanced prostate cancer; and (3) the screen-detected cohort, which included men age ≥ 65 years with screen-detected high-risk prostate cancer. We evaluated cause-specific and all-cause mortality using propensity score, instrumental variable (IV), and sensitivity analyses. Results In the RCT cohort, ADT plus RT was associated with reduced cause-specific and all-cause mortality relative to ADT alone (cause-specific propensity score–adjusted hazard ratio [HR], 0.43; 95% CI, 0.37 to 0.49; all-cause propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). Effectiveness estimates for the RCT cohort were not significantly different from those from randomized trials (P > .1). In the elderly and screen-detected cohorts, ADT plus RT was also associated with reduced cause-specific and all-cause mortality. IV analyses produced estimates similar to those from propensity score–adjusted methods. Conclusion Older men with locally advanced or screen-detected high-risk prostate cancer who receive ADT alone risk decrements in cause-specific and overall survival. PMID:25559808

  16. Efficacy and Factors Affecting Outcome of Gemcitabine Concurrent Chemoradiotherapy in Patients With Locally Advanced Pancreatic Cancer

    SciTech Connect

    Huang, P.-I.; Chao, Yee; Li, C.-P.; Lee, R.-C.; Chi, K.-H.; Shiau, C.-Y.; Wang, L.-W.; Yen, S.-H.

    2009-01-01

    Purpose: To evaluate the efficacy and prognostic factors of gemcitabine (GEM) concurrent chemoradiotherapy (CCRT) in patients with locally advanced pancreatic cancer. Methods and Materials: Between January 2002 and December 2005, 55 patients with locally advanced pancreatic cancer treated with GEM (400 mg/m{sup 2}/wk) concurrently with radiotherapy (median dose, 50.4 Gy; range, 26-61.2) at Taipei Veterans General Hospital were enrolled. GEM (1,000 mg/m{sup 2}) was continued after CCRT as maintenance therapy once weekly for 3 weeks and repeated every 4 weeks. The response, survival, toxicity, and prognostic factors were evaluated. Results: With a median follow-up of 10.8 months, the 1- and 2-year survival rate was 52% and 19%, respectively. The median overall survival (OS) and median time to progression (TTP) was 12.4 and 5.9 months, respectively. The response rate was 42% (2 complete responses and 21 partial responses). The major Grade 3-4 toxicities were neutropenia (22%) and anorexia (19%). The median OS and TTP was 15.8 and 9.5 months in the GEM CCRT responders compared with 7.5 and 3.5 months in the nonresponders, respectively (both p < 0.001). The responders had a better Karnofsky performance status (KPS) (86 {+-} 2 vs. 77 {+-} 2, p = 0.002) and had received a greater GEM dose intensity (347 {+-} 13 mg/m{sup 2}/wk vs. 296 {+-} 15 mg/m{sup 2}/wk, p = 0.02) than the nonresponders. KPS and serum carbohydrate antigen 19-9 were the most significant prognostic factors of OS and TTP. Conclusion: The results of our study have shown that GEM CCRT is effective and tolerable for patients with locally advanced pancreatic cancer. The KPS and GEM dose correlated with response. Also, the KPS and CA 19-9 level were the most important factors affecting OS and TTP.

  17. Neoadjuvant chemoradiotherapy followed by surgery in locally advanced squamous cell carcinoma of the vulva

    PubMed Central

    GAUDINEAU, A.; WEITBRUCH, D.; QUETIN, P.; HEYMANN, S.; PETIT, T.; VOLKMAR, P.; BODIN, F.; VELTEN, M.; RODIER, J.F.

    2012-01-01

    Alternative therapies have been sought to alleviate mutilation and morbidity associated with surgery for vulvar neoplasms. Our prime objective was to assess tumor absence in pathological vulvar and nodal specimens following neoadjuvant chemoradiotherapy in locally advanced vulvar neoplasms. Data were retrospectively collected from January 2001 to May 2009 from 22 patients treated with neoadjuvant therapy for locally advanced squamous cell carcinoma of the vulva. Neoadjuvant treatment consisted of inguino-pelvic radiotherapy (50 Gy) in association with chemotherapy when possible. Surgery occurred at intervals of between 5 to 8 weeks. The median age of patients at diagnosis was 74.1 years. All patients were primarily treated with radiotherapy and 15 received a concomitant chemotherapy. Additionally, all patients underwent radical vulvectomy and bilateral inguino-femoral lymphadenectomy. Tumor absence in the vulvar and nodal pathological specimens was achieved for 6 (27%) patients, while absence in the vulvar pathological specimens was only achieved for 10 (45.4%) patients. Postoperative follow-up revealed breakdown of groin wounds, vulvar wounds and chronic lymphedema in 3 (14.3%), 7 (31.8%) and 14 cases (63.6%), respectively. Within a median follow-up time of 2.3 years [interquartile range (IQR), 0.6–4.6], 12 (54.6%) patients experienced complete remission and 6 cases succumbed to metastatic evolution within a median of 2.2 years (IQR, 0.6–4.6), with 1 case also experiencing perineal recurrence. Median survival time, estimated using the Kaplan-Meier method, was 5.1 years (IQR, 1.0–6.8). We suggest that neoadjuvant chemoradiotherapy may represent a reliable and promising strategy in locally advanced squamous cell carcinoma of the vulva. PMID:23205089

  18. Review of the economic evaluations of hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Androgen deprivation therapy (ADT) is used as first-line therapy for locally advanced or metastatic prostate cancer aiming to reduce testosterone to castrate levels. The authors present an overview of the existing cost-effectiveness studies of ADT in prostate cancer. Cost-effectiveness of ADT was reviewed using a systematic search of the peer-reviewed literature, as well as research abstracts presented at various scientific and industry meetings. Most cost-effectiveness analyses of ADT reported results within the accepted societal threshold of US$50,000 cost/quality-adjusted life year needed to adopt new technology. PMID:23570436

  19. Combination chemotherapy followed by surgery or radiotherapy in patients with locally advanced cervical cancer.

    PubMed

    Kirsten, F; Atkinson, K H; Coppleson, J V; Elliott, P M; Green, D; Houghton, R; Murray, J C; Russell, P; Solomon, H J; Friedlander, M

    1987-06-01

    Forty-seven patients with locally advanced cervical cancer at high risk of relapse received three cycles of chemotherapy with PVB (cisplatin, vinblastine and bleomycin) before definitive local treatment with either radical surgery or radiotherapy. Thirty-one of the 47 patients (66%) responded to initial chemotherapy, and 11 of them have relapsed compared with 13 of the 16 non-responders. Median time to recurrence was 31 weeks for PVB non-responders but has not yet been reached for PVB responders. After a median follow-up of 128 weeks, 14 of the 31 responders (45%) are alive and disease free compared with 3 of the 16 non-responders (19%). There was a positive correlation between response to chemotherapy and subsequent response to radiotherapy. PVB was in general well tolerated although one death is probably attributable to chemotherapy. A randomized study comparing radiotherapy alone with initial PVB chemotherapy followed by radiotherapy is in progress. PMID:2441736

  20. [R0 Resection of Locally Advanced Pancreatic Cancer after Combination Chemotherapy with Gemcitabine and S-1].

    PubMed

    Kametaka, Hisashi; Makino, Hironobu; Fukada, Tadaomi; Seike, Kazuhiro; Koyama, Takashi; Hasegawa, Akio

    2015-11-01

    A 68-year-old female was referred to our institution in October 2014 for additional therapy for cancer of the head of the pancreas. Utilizing a computed tomography scan, he was initially diagnosed with locally advanced unresectable cancer because of massive invasion to the superior mesenteric artery (SMA). Combination chemotherapy consisting of gemcitabine and S-1 was administrated for 10 months. Since the tumor was remarkably reduced after chemotherapy, pancreaticoduodenectomy combined with portal vein resection was performed. Since the histopathological findings indicated few residual cancer tissues, our chemotherapy was considered dramatically effective. The postoperative course was uneventful and the patient remains well and without any recurrences 14 months after the surgery. We therefore report a case of locally unresectable pancreatic cancer, which achieved R0 resection after combination chemotherapy with gemcitabine and S-1. PMID:26805123

  1. Measurement of sorafenib plasma concentration by high-performance liquid chromatography in patients with advanced hepatocellular carcinoma: is it useful the application in clinical practice? A pilot study.

    PubMed

    Fucile, Carmen; Marenco, Simona; Bazzica, Marco; Zuccoli, Maria Laura; Lantieri, Francesca; Robbiano, Luigi; Marini, Valeria; Di Gion, Paola; Pieri, Giulia; Stura, Paola; Martelli, Antonietta; Savarino, Vincenzo; Mattioli, Francesca; Picciotto, Antonino

    2015-01-01

    Pharmacokinetics and dose-finding studies on sorafenib were conducted on heterogeneous groups of patients with solid tumors. Portal hypertension, gut motility impairment and altered bile enterohepatic circulation may explain different sorafenib toxicological profile in cirrhotic patients. This study evaluated sorafenib plasma concentration in a homogeneous group of cirrhotic patients with hepatocellular carcinoma (HCC). Sorafenib concentrations were determined by liquid chromatography in 12 consecutive patients. Data have been evaluated by the generalized estimating equations method (p value statistical level was set at α = 0.05). (1) There were not significant differences between sorafenib concentrations in patients who tolerate the full dose versus patients with reduced dose due to toxicity; (2) the average sorafenib concentrations measured 3 h after the morning dosing were lower than those measured 12 h after the evening dosing (p = 0.005); (3) sorafenib concentrations decrease overtime (p < 10(-4)); (4) it has been found an association between the development of severe adverse reactions and sorafenib concentrations (p < 10(-5)). The relationship between dose and concentration of sorafenib in HCC patients is poor and not clinically predictable, confirming the variability both in the maximum tolerated dose and in plasma concentrations. Several factors may influence the pharmacokinetics in patients with liver disease. This may explain the inter-patient variability of concentrations and the lack of differences in concentration at different dosages. It could be interesting to extend the series of HCC patients to enhance information on the kinetics of the drug; furthermore, to establish a threshold of plasma sorafenib concentrations to predict severe adverse reactions would be clinically useful. PMID:25429830

  2. Impact of more detailed categorization of shrinkage or progression ratio at initial imaging response after sorafenib treatment in advanced hepatocellular carcinoma patients

    PubMed Central

    Wada, Yoshiyuki; Takami, Yuko; Tateishi, Masaki; Ryu, Tomoki; Mikagi, Kazuhiro; Saitsu, Hideki

    2015-01-01

    Background Sorafenib therapy improves survival in unresectable hepatocellular carcinoma (HCC) patients without an objective response. The present study investigated whether the initial imaging response might be a prognostic indicator after administration of sorafenib therapy in HCC patients. Patients and methods This retrospective study reviewed unresectable HCC patients undergoing sorafenib therapy. Patients evaluated without complete response, partial response (PR), or progressive disease (PD) at the initial imaging response evaluation by modified Response Evaluation Criteria in Solid Tumors were divided into three groups according to more detailed categorization of the shrinkage/progression ratio in initial imaging response. A comparison of progression-free and overall survival among these groups was performed. Results Of the 43 non-PR non-PD patients with target lesions, ten (23.3%) exhibited mild response (MR; −30% to −5%), 14 (32.6%) exhibited no change (NC; −5% to +5%), and 19 (44.2%) exhibited mild-PD (MPD; +5% to +20%). There was no statistical difference in progression-free or overall survival between MR and NC patients. The median progression-free survivals in NC+MR and mild-PD patients were 15.0 and 5.3 months, respectively (P<0.01), and the median survival times were 31.9 and 17.1 months, respectively (P<0.001). In multivariate analysis, etiology (hepatitis C virus) and initial imaging response (MR+NC) was identified as an independently good prognostic factor. Conclusion More detailed categorization of shrinkage or progression at the initial imaging response evaluation may be a useful marker for predicting sorafenib treatment outcomes in HCC patients. If the initial imaging response is not progression but stability, sorafenib may have a survival benefit. PMID:26586953

  3. Edge localized mode characteristics during edge localized mode mitigation by supersonic molecular beam injection in Korea Superconducting Tokamak Advanced Research

    SciTech Connect

    Lee, H. Y.; Hong, J. H.; Jang, J. H.; Park, J. S.; Choe, Wonho; Hahn, S. H.; Bak, J. G.; Lee, J. H.; Ko, W. H.; Lee, K. D.; Lee, S. H.; Lee, H. H.; Juhn, J.-W.; Kim, H. S.; Yoon, S. W.; Han, H.; Ghim, Y.-C.

    2015-12-15

    It has been reported that supersonic molecular beam injection (SMBI) is an effective means of edge localized mode (ELM) mitigation. This paper newly reports the changes in the ELM, plasma profiles, and fluctuation characteristics during ELM mitigation by SMBI in Korea Superconducting Tokamak Advanced Research. During the mitigated ELM phase, the ELM frequency increased by a factor of 2–3 and the ELM size, which was estimated from the D{sub α} amplitude, the fractional changes in the plasma-stored energy and the line-averaged electron density, and divertor heat flux during an ELM burst, decreased by a factor of 0.34–0.43. Reductions in the electron and ion temperatures rather than in the electron density were observed during the mitigated ELM phase. In the natural ELM phase, frequency chirping of the plasma fluctuations was observed before the ELM bursts; however, the ELM bursts occurred without changes in the plasma fluctuation frequency in the mitigated ELM phase.

  4. Pathologic response to neoadjuvant treatment in locally advanced rectal cancer and impact on outcome

    PubMed Central

    Davis, Sidney; Mohebbi, Mohammadreza; Sugamaran, Bhuvana; Porter, Ian W.; Bell, Stephen; Warrier, Satish K.; Wale, Roger

    2016-01-01

    Background Downstaging and pathologic complete response (pCR) after chemoradiotherapy (CRT) may improve progression-free survival and overall survival (OS) after curative therapy of locally advanced adenocarcinoma of rectum. The purpose of this study is to evaluate the pathologic response subsequent to neoadjuvant chemoradiation in locally advanced rectal adenocarcinoma and any impact of response on oncological outcome [disease-free survival (DFS), OS]. Methods A total of 127 patients with histologically-proven rectal adenocarcinoma, locally advanced, were treated with preoperative radiotherapy and concurrent 5-fluorouracil (5 FU), and followed by curative surgery. Pathologic response to neoadjuvant treatment was evaluated by comparing pathologic TN (tumour and nodal) staging (yp) with pre-treatment clinical staging. DFS and OS were compared in patients with: pCR, partial pathologic response and no response to neoadjuvant therapy. Results 14.96% (19 patients) had a pCR, 58.27% [74] showed downstaging and 26.77% [34] had no change in staging. At follow-up (range, 4–9 years, median 6 years 2 months or 74 months), 17.32% [22] showed recurrence: 15.74% [20] distant metastasis, 1.57% [2] pelvic failure. 10.5% [2] of the patients with pCR showed distant metastasis, none showed local recurrence. In the downstaged group, nine developed distant failure and two had local recurrence (14.86%). Distant failure was seen in 26.47% [9] of those with no response to neoadjuvant treatment. DFS and OS rates for all groups were 82.67% and 88.97% respectively. Patients with pCR showed 89.47% DFS and 94.7% OS. In partial responders, DFS was 85.1% and OS was 90.5%. In non-responders, DFS and OS were 73.5% and 82.3% respectively. Patients with pCR had a significantly greater probability of DFS and OS than non-responders. Rectal cancer-related death was 11.02% [14]: one patient (5.26%) with pCR, 9.47% [7] in the downstaged group and 17.64% [6] of non-responders. Conclusions The majority

  5. Prognostic factors for hepatocellular carcinoma recurrence

    PubMed Central

    Colecchia, Antonio; Schiumerini, Ramona; Cucchetti, Alessandro; Cescon, Matteo; Taddia, Martina; Marasco, Giovanni; Festi, Davide

    2014-01-01

    The recurrence of hepatocellular carcinoma, the sixth most common neoplasm and the third leading cause of cancer-related mortality worldwide, represents an important clinical problem, since it may occur after both surgical and medical treatment. The recurrence rate involves 2 phases: an early phase and a late phase. The early phase usually occurs within 2 years after resection; it is mainly related to local invasion and intrahepatic metastases and, therefore, to the intrinsic biology of the tumor. On the other hand, the late phase occurs more than 2 years after surgery and is mainly related to de novo tumor formation as a consequence of the carcinogenic cirrhotic environment. Since recent studies have reported that early and late recurrences may have different risk factors, it is clinically important to recognize these factors in the individual patient as soon as possible. The aim of this review was, therefore, to identify predicting factors for the recurrence of hepatocellular carcinoma, by means of invasive and non-invasive methods, according to the different therapeutic strategies available. In particular the role of emerging techniques (e.g., transient elastography) and biological features of hepatocellular carcinoma in predicting recurrence have been discussed. In particular, invasive methods were differentiated from non-invasive ones for research purposes, taking into consideration the emerging role of the genetic signature of hepatocellular carcinoma in order to better allocate treatment strategies and surveillance follow-up in patients with this type of tumor. PMID:24876717

  6. [A Case of Locally Advanced Rectal Cancer Curatively Resected Following Chemoradiotherapy].

    PubMed

    Kawahara, Yohei; Terada, Itsuro; Terai, Shiro; Yamamoto, Seiichi; Kaji, Masahide; Maeda, Kiichi; Shimizu, Koichi

    2015-11-01

    A man in his 70s was referred to our hospital with anorexia, weight loss, and constipation. After examination by computed tomography (CT), magnetic resonance imaging (MRI), and colonoscopy, he was diagnosed as having a locally advanced rectal cancer with abscess formation. Because CT and MRI indicated that the tumor had invaded the seminal vesicle, prostate, and sacrum, we diagnosed it as an unresectable tumor. We treated the abscesses around the tumor by sigmoid colostomy with administration of antibiotics. After control of the infection, the patient received systemic chemotherapy with capecitabine/oxaliplatin (XELOX) plus bevacizumab (BV). After the 5th courses of XELOX plus BV, the primary tumor showed a tendency to shrink, but invasion to the neighboring organs was still seen. Therefore, we treated him with chemoradiotherapy (CRT) using S-1. After completion of CRT with no significant adverse effects, the tumor invasion to the neighboring organs disappeared, and we performed a low anterior resection 9 weeks later. Pathological findings revealed that the tumor had shrunk remarkably and it was resected curatively, although a few tumor cells remained in the subserosal layer of the ulcerative scar caused by the CRT. His postoperative course was uneventful, and he underwent adjuvant chemotherapy with S-1 for 3 months after discharge. To date, no disease recurrence has been detected. We report a case of locally advanced rectal cancer, which was curatively resected following chemoradiotherapy, along with a short literature review. PMID:26805354

  7. Surgery is an essential component of multimodality therapy for patients with locally advanced esophageal adenocarcinoma

    PubMed Central

    Murphy, Caitlin C.; Correa, Arlene M.; Ajani, Jaffer A.; Komaki, Ritsuko U.; Welsh, James W.; Swisher, Stephen G.; Hofstetter, Wayne L.

    2016-01-01

    Background Experience with neoadjuvant chemoradiation (CXRT) has raised questions regarding the additional benefit of surgery after locally advanced esophageal adenocarcinoma patients achieve a clinical response to CXRT. We sought to quantify the value of surgery by comparing the overall (OS) and disease-free survival (DFS) of trimodality eligible patients treated with definitive CXRT versus CXRT followed by esophagectomy. Methods We identified 143 clinical stage III esophageal adenocarcinoma patients that were eligible for trimodality therapy. All patients successfully completed neoadjuvant CXRT and were considered appropriate candidates for resection. Patients that were medically inoperable were excluded. Cox regression models were used to identify significant predictors of survival. Results Among the 143 patients eligible for surgery after completing CXRT, 114 underwent resection and 29 did not. Poorly differentiated tumors (HR=2.041, 95% CI 1.235–3.373) and surgical resection (HR=0.504, 95% CI 0.283–0.899) were the only independent predictors of OS. Patients treated with surgery had a 50% and 54% risk reduction in overall and cancer-specific mortality, respectively. Median OS (41.2 months vs. 20.3 months, p=0.012) and DFS (21.5 months vs. 11.4 months, p=0.007) were significantly improved with the addition of surgery compared to definitive CXRT. Conclusions Surgery provides a significant survival benefit to trimodality-eligible esophageal adenocarcinoma patients with locally advanced disease. PMID:23715646

  8. Could preoperative short-course radiotherapy be the treatment of choice for localized advanced rectal carcinoma?

    PubMed

    Ciria, Juan Pablo; Eguiguren, Mikel; Cafiero, Sergio; Uranga, Intza; Diaz de Cerio, Ivan; Querejeta, Arrate; Urraca, Jose Maria; Minguez, Julian; Guimon, Elena; Puertolas, Jose Ramón

    2015-01-01

    Short-course preoperative radiotherapy (RT) is widely used in northern Europe for locally advanced resectable rectal cancer, but its role in the era of advanced imaging techniques is uncertain. Here, we reviewed articles and abstracts on SCRT published from 1974 through 2013 with the goal of identifying patients who might be best suited for short-course RT. We included relevant articles comparing surgery with or without preoperative radiation published before and after the advent of total mesorectal excision. We also analyzed two randomized trials directly comparing short-course RT with conventionally fractionated chemoradiation (the Polish Colorectal Study Group and the Trans-Tasman Radiation Oncology Group) that compared short-course RT with conventional chemoradiotherapy. We conclude from our review that short-course RT can be generally applied for operable rectal cancer and produces high rates of pelvic control with acceptable toxicity; it reduces local recurrence rates but does not increase overall survival. SCRT seems to be best used for tumors considered "low risk," i.e., those that are >5 cm from the anal margin, without circumferential margin involvement, and involvement of fewer than 4 lymph nodes. Whether sequential chemotherapy can further improve outcomes remains to be seen, as does the best time for surgery (immediately or 6-8 weeks after RT). We further recommend that selection of patients for short-course RT should be based on findings from magnetic resonance imaging or transrectal ultrasonography. PMID:25535578

  9. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma

    PubMed Central

    Borregales, Leonardo D.; Adibi, Mehrad; Thomas, Arun Z.; Wood, Christopher G.; Karam, Jose A.

    2015-01-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  10. Retrospective Analysis of Locally Advanced Noninflammatory Breast Cancer From Chennai, South India, 1990-1999

    SciTech Connect

    Shanta, Viswanathan Swaminathan, Rajaraman; Rama, Ranganathan M.Sc.; Radhika, Ramachandran M.S.

    2008-01-01

    Purpose: This was a retrospective observational study to elicit the outcome of the therapeutic strategy of concurrent neoadjuvant chemoradiotherapy protocol for locally advanced breast cancer. Methods and Materials: A large series of 1,117 consecutive cases of locally advanced breast cancer treated at the Cancer Institute (WIA), in Chennai, South India, between 1990 and 1999 and followed through 2004 formed the basis for this study. Disease-free survival was the main outcome, and nodal and tumor downstaging were the intermediate outcome measures studied. Results: Primary tumor downstaging was observed in 45% and nodal downstaging in 57.5%. The disease-free survival rate of nodal downstaged patients at 5, 10, and 15 years was 75%, 65%, and 58%, respectively. The corresponding rates for pre- and postoperative node-negative patients were 70%, 60%, and 59%. The best survival was seen among those who were tumor and node negative postoperatively. Nodal downstaging halved the risk of disease recurrence and death compared with node positivity, irrespective of tumor sterility. Conclusions: A randomized trial using cyclophosphamide, methotrexate, and 5-fluorouracil vs. an anthracycline-based regimen in the setting of concurrent chemoradiotherapy appears indicated. Additional preoperative chemotherapy to maximize nodal and tumor downstaging should be investigated. A change in postoperative chemotherapy according to nodal status could also be explored.

  11. Tumor Phosphatidylinositol-3-Kinase Signaling and Development of Metastatic Disease in Locally Advanced Rectal Cancer

    PubMed Central

    Ree, Anne Hansen; Kristensen, Annette Torgunrud; Saelen, Marie Grøn; de Wijn, Rik; Edvardsen, Hege; Jovanovic, Jovana; Abrahamsen, Torveig Weum; Dueland, Svein; Flatmark, Kjersti

    2012-01-01

    Background Recognizing EGFR as key orchestrator of the metastatic process in colorectal cancer, but also the substantial heterogeneity of responses to anti-EGFR therapy, we examined the pattern of composite tumor kinase activities governed by EGFR-mediated signaling that might be implicated in development of metastatic disease. Patients and Methods Point mutations in KRAS, BRAF, and PIK3CA and ERBB2 amplification were determined in primary tumors from 63 patients with locally advanced rectal cancer scheduled for radical treatment. Using peptide arrays with tyrosine kinase substrates, ex vivo phosphopeptide profiles were generated from the same baseline tumor samples and correlated to metastasis-free survival. Results Unsupervised clustering analysis of the resulting phosphorylation of 102 array substrates defined two tumor classes, both consisting of cases with and without KRAS/BRAF mutations. The smaller cluster group of patients, with tumors generating high ex vivo phosphorylation of phosphatidylinositol-3-kinase-related substrates, had a particularly aggressive disease course, with almost a half of patients developing metastatic disease within one year of follow-up. Conclusion High phosphatidylinositol-3-kinase-mediated signaling activity of the primary tumor, rather than KRAS/BRAF mutation status, was identified as a hallmark of poor metastasis-free survival in patients with locally advanced rectal cancer undergoing radical treatment of the pelvic cavity. PMID:23226389

  12. Neoadjuvant radiochemotherapy for locally advanced gastric cancer: Long-term results of a phase I trial

    SciTech Connect

    Allal, Abdelkarim S. . E-mail: abdelkarim.allal@hcuge.ch; Zwahlen, Daniel; Bruendler, Marie-Anne; Peyer, Raymond de; Morel, Philippe; Huber, Olivier; Roth, Arnaud D.

    2005-12-01

    Purpose: To assess the long-term results of radiation therapy (RT) when added preoperatively to systemic chemotherapy in patients with locally advanced gastric cancer. Methods and Materials: Patients presenting with T3-4 or N+ gastric cancer received two cycles of cisplatin 100 mg/m{sup 2} d1, 5FU 800 mg/m{sup 2} d1-4, and Leucovorin 60 mg twice daily d1-4; one cycle before and one concomitantly with hyperfractionated RT (median dose, 38.4; range, 31.2-45.6 Gy). All patients underwent a total or subtotal gastrectomy with D2 lymph node resection. Results: Nineteen patients were accrued and 18 completed the neoadjuvant therapeutic program. All patients were subsequently operated and no fatality occurred. At a mean follow-up of 8 years for the surviving patients, no severe late toxicity was observed. The 5-year locoregional control, disease-free, and overall survival were of 85%, 41%, and 35%, respectively. The peritoneum was the most frequent site of relapse. Among long terms survivors, no severe (Radiation Therapy Oncology Group Grade 3-4) late complication was reported. Conclusions: The present neoadjuvant treatment does not seem to increase the operative risk, nor the late side effects. The encouraging locoregional control rate suggests that the neoadjuvant approach should be considered for future trials in locally advanced gastric cancer. Also, the frequency of peritoneal recurrence stresses the need for a more efficient systemic or intraperitoneal treatment.

  13. Emerging therapies in the treatment of locally advanced squamous cell cancers of head and neck.

    PubMed

    Raza, Shahzad; Kornblum, Noah; Kancharla, Venkat P; Baig, Mahadi A; Singh, Amrit B; Kalavar, Madhumati

    2011-05-01

    Head and neck squamous cell cancers (HNSCCs) represent 4 to 5% of all solid malignancies. Despite improvements in diagnostic techniques, 60% of patients will present with locally advanced HNSCCs with a median survival of about 12 months and 5-year overall survival of approximately 10-40%. Recent clinical trials have altered the treatment landscape by refining existing forms of radiation, incorporation of IMRT, choice of chemotherapeutic agents, introduction of biological and targeted therapy, immunotherapy and gene therapy. Cetuximab, a monoclonal antibody directed against the human epidermal growth factor receptor (EGFR), has recently been approved in combination with RT in patients with locally advanced HNSCCs. Antiangiogenic therapies and tyrosine kinase inhibitors (gefitinib and erlotinib) have also shown promise in the clinical trials. Vandetanib, an antagonist of both vascular endothelial growth factor receptor (VEGFR) and the EGFR is currently being tested in phase II trial. New patents on hypoxia-inducible factor 1 alpha, mesenchymal-epithelial transition factor, insulin-like growth factor or the PI3K/AKT/mTOR pathway, farnesyl transferase inhibitors have shown promise in the management of HNSCCs. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains a fundamental challenge in the optimal selection of patients most likely to benefit from them. However, increase in efficacy comes at the cost of increased toxicity. The current review focuses on insight into recent patents and updates on the clinical trials using new investigational agents in the management for HNSCCs. PMID:21247406

  14. The role of neoadjuvant therapy in the management of locally advanced renal cell carcinoma.

    PubMed

    Borregales, Leonardo D; Adibi, Mehrad; Thomas, Arun Z; Wood, Christopher G; Karam, Jose A

    2016-04-01

    In the past decade, the armamentarium of targeted therapy agents for the treatment of metastatic renal cell carcinoma (RCC) has significantly increased. Improvements in response rates and survival, with more manageable side effects compared with interleukin 2/interferon immunotherapy, have been reported with the use of targeted therapy agents, including vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors (sunitinib, sorafenib, pazopanib, axitinib), mammalian target of rapamycin (mTOR) inhibitors (everolimus and temsirolimus) and VEGF receptor antibodies (bevacizumab). Current guidelines reflect these new therapeutic approaches with treatments based on risk category, histology and line of therapy in the metastatic setting. However, while radical nephrectomy remains the standard of care for locally advanced RCC, the migration and use of these agents from salvage to the neoadjuvant setting for large unresectable masses, high-level venous tumor thrombus involvement, and patients with imperative indications for nephron sparing has been increasingly described in the literature. Several trials have recently been published and some are still recruiting patients in the neoadjuvant setting. While the results of these trials will inform and guide the use of these agents in the neoadjuvant setting, there still remains a considerable lack of consensus in the literature regarding the effectiveness, safety and clinical utility of neoadjuvant therapy. The goal of this review is to shed light on the current body of evidence with regards to the use of neoadjuvant treatments in the setting of locally advanced RCC. PMID:27034725

  15. Preoperative indications for extended pancreatectomy for locally advanced pancreas cancer involving the portal vein.

    PubMed Central

    Ishikawa, O; Ohigashi, H; Imaoka, S; Furukawa, H; Sasaki, Y; Fujita, M; Kuroda, C; Iwanaga, T

    1992-01-01

    This retrospective study attempted to determine the indications for extended pancreatectomy for locally advanced carcinoma of the pancreas, in terms of postoperative prognosis. An extended pancreatectomy with portal vein or superior mesenteric vein (PV/SMV) resection and regional lymphadenectomy was performed in 35 of 50 consecutive cancers that extended into the retroperitoneal spaces and involved the PV or SMV. Among the many background factors in the 35 resected specimens, the degree of PV/SMV invasion by the cancer was most closely associated with prognosis, despite resection of all involved PV/SMV. This factor generally correlated with the preoperative findings on the portal phase of superior mesenteric arteriograph. In 17 selected patients in whom PV/SMV invasion had been angiographically both semicircular or less and 1.2 cm (1.4 cm on the film) or less in length, the 3-year survival rate was 59%. This survival rate was significantly higher than the 29% 3-year survival rate in all 35 patients (p less than 0.05). Conversely, among the 18 patients in whom invasion was angiographically either beyond semicircular or more than 1.2 cm (1.4 cm on the film) in length, there were no 1.5-year survivors, and this result was even worse than that of 15 nonresectable cases. Based on postoperative survival, the degrees of PV/SMV invasion on preoperative angiography (narrowing pattern and length) are good indicators for aggressive pancreatectomy for locally advanced pancreatic cancer. Images FIG. 2. PMID:1543394

  16. [Two Cases of Curative Resection of Locally Advanced Rectal Cancer after Preoperative Chemotherapy].

    PubMed

    Mitsuhashi, Noboru; Shimizu, Yoshiaki; Kuboki, Satoshi; Yoshitomi, Hideyuki; Kato, Atsushi; Ohtsuka, Masayuki; Shimizu, Hiroaki; Miyazaki, Masaru

    2015-11-01

    Reports of conversion in cases of locally advanced colorectal cancer have been increasing. Here, we present 2 cases in which curative resection of locally advanced rectal cancer accompanied by intestinal obstruction was achieved after establishing a stoma and administering chemotherapy. The first case was of a 46-year-old male patient diagnosed with upper rectal cancer and intestinal obstruction. Because of a high level of retroperitoneal invasion, after establishing a sigmoid colostomy, 13 courses of mFOLFOX6 plus Pmab were administered. Around 6 months after the initial surgery, low anterior resection for rectal cancer and surgery to close the stoma were performed. Fourteen days after curative resection, the patient was discharged from the hospital. The second case was of a 66-year-old male patient with a circumferential tumor extending from Rs to R, accompanied by right ureter infiltration and sub-intestinal obstruction. After establishing a sigmoid colostomy, 11 courses of mFOLFOX6 plus Pmab were administered. Five months after the initial surgery, anterior resection of the rectum and surgery to close the stoma were performed. Twenty days after curative resection, the patient was released from the hospital. No recurrences have been detected in either case. PMID:26805302

  17. Bevacizumab in the pre-operative treatment of locally advanced rectal cancer: A systematic review

    PubMed Central

    Fornaro, Lorenzo; Caparello, Chiara; Vivaldi, Caterina; Rotella, Virginia; Musettini, Gianna; Falcone, Alfredo; Baldini, Editta; Masi, Gianluca

    2014-01-01

    Despite advances in the management of patients with locally advanced, non-metastatic rectal adenocarcinoma (LARC), prognosis remains largely unsatisfactory due to a high rate of distant relapse. In fact, currently available neoadjuvant protocols, represented by fluoropyrimidine-based chemo-radiotherapy (CT-RT) or short-course RT, together with improved surgical techniques, have largely reduced the risk of local relapse, with limited impact on distant recurrence. Available results of phase III trials with additional cytotoxic agents combined with standard CT-RT are disappointing, as no significant reduction in the risk of recurrence has been demonstrated. In order to improve the control of micrometastatic disease, integrating targeted agents into neoadjuvant treatment protocols thus offers a rational approach. In particular, the antiangiogenic agent bevacizumab has demonstrated synergistic activity with both CT and RT in pre-clinical and clinical models, and thus may represent a suitable companion in the neoadjuvant treatment of LARC. Preliminary results of phase I-II clinical studies are promising and suggest potential clinical parameters and molecular predictive biomarkers useful for patient selection: treatment personalization is indeed the key in order to maximize the benefit while reducing the risk of more complex neoadjuvant treatment schedules. PMID:24876730

  18. Early transient radiation-induced brachial plexopathy in locally advanced head and neck cancer

    PubMed Central

    Etiz, Durmus

    2016-01-01

    Aim of the study Early transient brachial plexopathy following radiotherapy (RT) in patients with head and neck cancer may be underreported and associated with a dose-response. Our purpose was to determine the incidence of early transient radiation-ınduced brachial plexopathy (RIBP) in patients receiving primary RT (± chemotherapy) for locally advanced head and neck cancer (HNC). Material and methods Twenty-seven locally advanced HNC patients who have no finding of brachial plexopathy at the diagnosis were evaluated 3 times by a specifically developed 13-item questionnaire for determining early transient RIBP. The 54 brachial plexus in 27 patients were delineated and dose volume histograms were calculated. Results Median follow-up period was 28 (range: 15–40) months. The mean BP volume was 7.9 ±3.6 cm3, and the mean and maximum doses to the BP were 45.3 (range: 32.3–59.3) Gy, and 59.4 (range: 41.4–70.3) Gy, respectively. Maximum dose to the BP was ≥ 70 Gy only in 2 nasopharyngeal cancer patients. Two (7%) early transient RIBP were reported at 7th and 8th month after RT under maximum 67.17 and 55.37 Gy, and mean 52.95 and 38.60 Gy RT doses. Conclusions Two (7%) early RIBP were seen in the patient group, although brachial plexus maximum doses were ≥ 66 Gy in 75% of patients. PMID:27095943

  19. Whole pelvic helical tomotherapy for locally advanced cervical cancer: technical implementation of IMRT with helical tomothearapy

    PubMed Central

    2009-01-01

    Background To review the experience and to evaluate the treatment plan of using helical tomotherapy (HT) for the treatment of cervical cancer. Methods Between November 1st, 2006 and May 31, 2009, 10 cervical cancer patients histologically confirmed were enrolled. All of the patients received definitive concurrent chemoradiation (CCRT) with whole pelvic HT (WPHT) followed by brachytherapy. During WPHT, all patients were treated with cisplatin, 40 mg/m2 intravenously weekly. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). Results The mean survival was 25 months (range, 3 to 27 months). The actuarial overall survival, disease-free survival, locoregional control and distant metastasis-free rates at 2 years were 67%, 77%, 90% and 88%, respectively. The average of uniformity index and conformal index was 1.06 and 1.19, respectively. One grade 3 of acute toxicity for diarrhea, thrombocytopenia and three grade 3 leucopenia were noted during CCRT. Only one grade 3 of subacute toxicity for thrombocytopenia was noted. There were no grade 3 or 4 subacute toxicities of anemia, leucopenia, genitourinary or gastrointestinal effects. Compared with conventional whole pelvic radiation therapy (WPRT), WPHT decreases the mean dose to rectum, bladder and intestines successfully. Conclusion HT provides feasible clinical outcomes in locally advanced cervical cancer patients. Long-term follow-up and enroll more locally advanced cervical carcinoma patients by limiting bone marrow radiation dose with WPHT technique is warranted. PMID:20003321

  20. [A Case of Successful Curative Resection Following Downsizing Chemotherapy in Initially Unresectable Locally Advanced Gallbladder Carcinoma].

    PubMed

    Shinmura, Kazuyasu; Kaiho, Takashi; Yanagisawa, Shinji; Okamoto, Ryo; Nishimura, Masaki; Kobayashi, Soichi; Okaniwa, Akira; Mun, Yangi; Tsuchiya, Shunichi; Chiba, Ryoji

    2015-11-01

    A 58-year-old woman was referred to our hospital with high fever and right upper abdominal pain. Abdominal computed tomography (CT) revealed a bulky tumor of the gallbladder with liver invasion, metastases to para-aortic lymph nodes, and extensive infiltration to Glisson's sheath. The tumor was initially considered to be unresectable locally advanced gallbladder carcinoma with inflammation, and she received 6 courses of chemotherapy with gemcitabine plus cisplatin. Subsequently, the inflammation was extinguished, and CT showed the main tumor shrunk and the Glisson's sheath infiltration disappeared; however, a liver metastasis existed in segment 5. Thus, S4a plus S5 hepatic segmentectomy with extrahepatic bile duct resection and regional and para-aortic lymphadenectomy was performed. The pathological diagnosis was pT3a, pN1, pM1 (Hep, LYM), fStage ⅣB. Curative resection was then performed. If selected according to their response to downsizing chemotherapy, conversion therapy might therefore be an effective multidisciplinary treatment for patients with initially unresectable locally advanced gallbladder carcinoma. PMID:26805152

  1. Quantitative ultrasound characterization of locally advanced breast cancer by estimation of its scatterer properties

    SciTech Connect

    Tadayyon, Hadi; Sadeghi-Naini, Ali; Czarnota, Gregory; Wirtzfeld, Lauren; Wright, Frances C.

    2014-01-15

    Purpose: Tumor grading is an important part of breast cancer diagnosis and currently requires biopsy as its standard. Here, the authors investigate quantitative ultrasound parameters in locally advanced breast cancers that can potentially separate tumors from normal breast tissue and differentiate tumor grades. Methods: Ultrasound images and radiofrequency data from 42 locally advanced breast cancer patients were acquired and analyzed. Parameters related to the linear regression of the power spectrum—midband fit, slope, and 0-MHz-intercept—were determined from breast tumors and normal breast tissues. Mean scatterer spacing was estimated from the spectral autocorrelation, and the effective scatterer diameter and effective acoustic concentration were estimated from the Gaussian form factor. Parametric maps of each quantitative ultrasound parameter were constructed from the gated radiofrequency segments in tumor and normal tissue regions of interest. In addition to the mean values of the parametric maps, higher order statistical features, computed from gray-level co-occurrence matrices were also determined and used for characterization. Finally, linear and quadratic discriminant analyses were performed using combinations of quantitative ultrasound parameters to classify breast tissues. Results: Quantitative ultrasound parameters were found to be statistically different between tumor and normal tissue (p < 0.05). The combination of effective acoustic concentration and mean scatterer spacing could separate tumor from normal tissue with 82% accuracy, while the addition of effective scatterer diameter to the combination did not provide significant improvement (83% accuracy). Furthermore, the two advanced parameters, including effective scatterer diameter and mean scatterer spacing, were found to be statistically differentiating among grade I, II, and III tumors (p = 0.014 for scatterer spacing, p = 0.035 for effective scatterer diameter). The separation of the tumor

  2. Clinically Apparent Internal Mammary Nodal Metastasis in Patients With Advanced Breast Cancer: Incidence and Local Control

    SciTech Connect

    Zhang Yujing; Oh, Julia L.; Whitman, Gary J.

    2010-07-15

    Purpose: To investigate the incidence and local control of internal mammary lymph node metastases (IMN+) in patients with clinical N2 or N3 locally advanced breast cancer. Methods and Materials: We retrospectively reviewed the records of 809 breast cancer patients diagnosed with advanced nodal disease (clinical N2-3) who received radiation treatment at our institution from January 2000 December 2006. Patients were considered IMN+ on the basis of imaging studies. Results: We identified 112 of 809 patients who presented with IMN+ disease (13.8%) detected on ultrasound, computed tomography (CT), positron emission tomography/CT (PET/CT), and/or magnetic resonance imaging (MRI) studies. All 112 patients with IMN+ disease received anthracycline and taxane-based chemotherapy. Neoadjuvant chemotherapy (NCT) resulted in a complete response (CR) on imaging studies of IMN disease in 72.1% of patients. Excluding 16 patients with progressive disease, 96 patients received adjuvant radiation to the breast or the chest wall and the regional lymphatics including the IMN chain with a median dose of 60 Gy if the internal mammary lymph nodes normalized after chemotherapy and 66 Gy if they did not. The median follow-up of surviving patients was 41 months (8-118 months). For the 96 patients able to complete curative therapy, the actuarial 5-year IMN control rate, locoregional control, overall survival, and disease-free survival were 89%, 80%, 76%, and 56%. Conclusion: Over ten percent of patients with advanced nodal disease will have IMN metastases on imaging studies. Multimodality therapy including IMN irradiation achieves excellent rates of control in the IMN region and a DFS of more than 50% after curative treatment.

  3. Early Decreases in α-Fetoprotein and Des-γ-carboxy Prothrombin Predict the Antitumor Effects of Hepatic Transarterial Infusion Chemotherapy with Cisplatin (CDDP) Powder in Patients with Advanced Hepatocellular Carcinoma.

    PubMed

    Hatanaka, Takeshi; Kakizaki, Satoru; Shimada, Yasushi; Takizawa, Daichi; Katakai, Kenji; Yamazaki, Yuichi; Sato, Ken; Kusano, Motoyasu; Yamada, Masanobu

    2016-01-01

    Objective We retrospectively investigated the relationship between the tumor response and serial changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) during hepatic arterial infusion of a cisplatin powder formulation (CDDP powder) in patients with advanced hepatocellular carcinoma (HCC). Methods Seventy-six advanced HCC patients were analyzed. All HCC patients received high-concentration cisplatin (1.43 mg/mL) via the haptic artery at a dose of 65 mg/m(2). AFP and DCP were measured at baseline and four to eight weeks after treatment, and the antitumor responses were evaluated according to the response evaluation criteria in solid tumours (RECIST) criteria after one or two courses of treatment. The patients were classified into two groups, a decreased group and a non-decreased group, according to the change in the serum levels of AFP and DCP at four to eight weeks compared to baseline. Results The response to treatment of the decreased group (n=16) and non-decreased group (n=60) was complete response/partial response/stable disease/progressive disease (CR/PR/SD/PD) in 4/4/5/3 and 1/11/8/40 patients, respectively. The response rate and disease control rate of the decreased group were significantly higher than those of the non-decreased group (p=0.016 and p<0.001, respectively). The median survival time (MST) of the decreased/non-decreased groups were 25.9/10.6 months, respectively. The cumulative survival rates for the decreased group were significantly higher than those of the non-decreased group (p=0.042). In the multivariate analysis, vascular invasion and the decreased group were significant factors that affected the therapeutic efficacy. Conclusion A decrease in the levels of AFP and DCP after the first treatment with CDDP powder is a good predictor for the antitumor effect and the prognosis. PMID:27522991

  4. Neoadjuvant chemotherapy in the combined modality approach of locally advanced nonmetastatic breast cancer.

    PubMed

    Swain, S M; Sorace, R A; Bagley, C S; Danforth, D N; Bader, J; Wesley, M N; Steinberg, S M; Lippman, M E

    1987-07-15

    We have treated 76 patients with locally advanced breast cancer, 31 with stage IIIA, 41 with stage IIIB, and 4 with stage IV disease, with primary induction chemotherapy including an attempted hormonal synchronization in 70 patients. All were treated to maximum objective clinical response before proceeding to any local therapy. Patients achieving a complete response with a negative repeat biopsy generally received radiation therapy while patients with residual disease, partial response (PR) or no change (NC) status received debulking surgery prior to radiation therapy. Regardless of response to induction chemotherapy, patients received at least 6 additional months of chemotherapy following local therapy. Initial doses of combination chemotherapy were escalated to targeted myelosuppression. The objective response rate to induction chemotherapy was 93% with 49% complete response (CR), 44% PR, and 7% NC. The median numbers of cycles of chemotherapy to achieve a CR, PR, or NC were 5, 3, and 5, respectively. Three patients who currently have PRs are still on chemotherapy with continued tumor regression. Of 37 patients achieving a CR to chemotherapy, 35 were assessed by biopsies to determine pathological evidence of response. Twenty-three of the 37 patients (62%) were proven to be complete responders with negative biopsies. Twenty-four patients have relapsed, 6 with stage IIIA, 16 with stage IIIB, and 2 with stage IV. Five patients have had locoregional relapses alone, 4 locoregional and distant, and 15 distant alone. Median time to progression is 35.9 months for stage IIIA and 34.2 months for stage IIIB. Median survival is 35.3 months for stage IIIB and is indeterminate for stage IIIA. This aggressive primary chemotherapy regimen with hormonal synchronization followed by local therapy appears to provide excellent local control and encouraging early results on systemic disease control. PMID:3036348

  5. What is the correct staging and treatment strategy for locally advanced prostate cancer extending to the bladder?

    PubMed

    Yüksel, Özgür Haki; Verit, Ayhan; Ürkmez, Ahmet

    2015-06-01

    In locally advanced prostate cancer with bladder invasion, frequently encountered problems such as bleeding, urinary retention, hydronephrosis, and pain create distress for the patients. Therefore patients' quality of life is disrupted and duration of hospitalization is prolonged. Relevant literature about accurate staging and treatment of locally advanced prostate cancer with bladder invasion was investigated. Locally advanced prostate cancer can present as a large-volume aggressive tumor extending beyond boundaries of prostate gland, and involving neighboring structures which can be involved as recurrence(s) following initial local therapy. Survival times of these patients can range between 5 and 8 years. Their common characteristics are adverse and severe local symptoms unfavorably affecting quality of life Control of local symptoms and their effective palliation are independent clinical targets influencing survival outcomes of these patients. The treatment outcomes of locally advanced prostate cancer into the bladder are currently debatable. Although in the current TNM classification, it is defined in T4a, we think that this may be categorized as a subgroup of T3 and thus encourage surgeons for the indication of radical surgeries (radical prostatectomy, radical cystoprostatectomy) in selected patient populations after discussing issues concerning consequences of the treatment alternatives, and expectations with the patients. Cystoprostatectomy followed by immediate androgen deprivation therapy may be a feasible option for selected patients with previously untreated prostate cancer involving the bladder neck because of excellent local control and long term survival. PMID:26150029

  6. Should needle localization breast biopsy give way to the new technology; the advanced breast biopsy instrumentation.

    PubMed

    Hawasli, A; Zonca, S; Watt, C; Rebecca, A

    2000-07-01

    Between July 1995 and June 1997, 114 consecutive women underwent 118 breast biopsies for nonpalpable lesions. A limited procedure room and local anesthesia were used in 96.5 per cent of patients. Intravenous access was not established in 95 per cent of patients. Oral diazepam was given to 51 per cent of patients. Needle localization technique was used with a success rate of 97.5 per cent and average operative time of 18 minutes. Breast carcinoma was found in 29 (24.6 per cent) biopsies. A review of 99 of the 118 mammograms showed only 45 per cent of the lesions being amenable to the new technology, the advanced breast biopsy instrumentation. Advantages of the needle localization include short operative time; supine position for the patient; easy access to control bleeding; ability to choose a cosmetic site for the skin incision; minimal tissue removal before reaching the lesion; ability to maintain a sterile field; and applicability to almost any mammographic lesion identified, whether single or multiple. Disadvantages include the need for a separate procedure to place the wire and potential of missing the lesion in 2.5 per cent, requiring additional surgery. PMID:10917475

  7. Irreversible electroporation in the treatment of locally advanced pancreas and liver metastases of colorectal carcinoma

    PubMed Central

    Wichtowski, Mateusz; Nowaczyk, Piotr; Kocur, Jacek

    2016-01-01

    Aim of the study Irreversible electroporation is a new, non-thermal ablation technique in the treatment of parenchymal organ tumors which uses short high voltage pulses of electricity in order to induce apoptosis of targeted cells. In this paper the application of this method of treatment in locally advanced pancreatic cancer (LAPC) and liver cancer is analyzed. Material and methods Between 04.2014 and 09.2014 two patients with LAPC and one with colorectal liver metastasis (CRLM) were qualified for treatment with irreversible electroporation. Both patients remained under constant observation and control. PubMed/Medline, Embase and Google Scholar databases were searched and eight original reports on irreversible electroporation of pancreatic and liver tumors based on the biggest groups of patients were found. Results Two patients with LAPC and one with CRLM were qualified for ablation with irreversible electroporation. In all three patients a successful irreversible electroporation (IRE) procedure of the whole tumor was conducted. In the minimum seven-month follow-up 100% local control was achieved – without progression. In the literature review the local response to treatment ranged from 41% to 100%. The event-free survival rate in six-month observation was 94%. Conclusions Ablation with irreversible electroporation is a new non-thermal ablation technique which has been demonstrated, both in the previously published studies and in the cases described in this paper, as a safe and efficient therapeutic method for patients with LAPC and CRLM. PMID:27095938

  8. Role of radiotherapy in the management of hepatocellular carcinoma: A systematic review

    PubMed Central

    Kalogeridi, Maria-Aggeliki; Zygogianni, Anna; Kyrgias, George; Kouvaris, John; Chatziioannou, Sofia; Kelekis, Nikolaos; Kouloulias, Vassilis

    2015-01-01

    Many patients with hepatocellular carcinoma (HCC) present with advanced disease, not amenable to curative therapies such as surgery, transplantation or radiofrequency ablation. Treatment options for this group of patients include transarterial chemoembolization (TACE) and radiation therapy. Especially TACE, delivering a highly concentrated dose of chemotherapy to tumor cells while minimizing systemic toxicity of chemotherapy, has given favorable results on local control and survival. Radiotherapy, as a therapeutic modality of internal radiation therapy with radioisotopes, has also achieved efficacious tumor control in advanced disease. On the contrary, the role of external beam radiotherapy for HCC has been limited in the past, due to the low tolerance of surrounding normal liver parenchyma. However, technological innovations in the field of radiotherapy treatment planning and delivery, have provided the means of delivering radical doses to the tumor, while sparing normal tissues. Advanced and highly conformal radiotherapy approaches such as stereotactic body radiotherapy and proton therapy, evaluated for efficacy and safety for HCC, report encouraging results. In this review, we present the role of radiotherapy in hepatocellular carcinoma patients not suitable for radical treatment. PMID:25625001

  9. Determinants of Quality Care and Mortality for Patients With Locally Advanced Cervical Cancer in Virginia

    PubMed Central

    Showalter, Timothy N.; Camacho, Fabian; Cantrell, Leigh A.; Anderson, Roger T.

    2016-01-01

    Abstract Outcomes for patients with locally advanced cervical cancer are influenced by receipt of all indicated components of quality care: early diagnosis and receipt of external beam radiation therapy, chemotherapy, and brachytherapy. We performed an observational cohort study to evaluate receipt of quality cancer care and mortality after cancer diagnosis among patients with locally advanced cervical cancer in Virginia. We queried the Virginia state cancer registry to identify patients with International Federation of Gynecology and Obstetrics Stage IB-IVA cervical cancer who were diagnosed during 2002 to 2012. We evaluated the influence of tumor-related, demographic, and geospatial factors on the receipt of indicated therapies and mortality. Treatment quality score of 0 to 3 was defined based upon the extent of receipt of the components of indicated therapy. A total of 1048 patients were identified; 33.1% received all 3 components of treatment and only 54.0% received brachytherapy. Predictors of higher quality score included younger age group versus 66+ years at diagnosis (18–42 odds ratio [OR] = 12.3, 95% confidence interval: 6.6, 23.0; 42–53 OR = 5.6, CI: 3.3, 9.5; 53–66 OR = 5.5, CI: 3.3, 9.1), lower tumor stages versus IVA (IB2 OR = 3.3, CI: 1.8, 6.2; II OR = 2.7, CI: 1.6, 4.5; IIIx OR = 2.1, CI: 1.3, 3.6), and treatment at a high-volume facility (OR 2.2, CI: 1.2, 4.2). Predictors of increased mortality included earlier year of diagnosis, higher tumor stage, treatment at a lower volume facility, and lower treatment quality score. In a cohort of locally advanced cervical cancer patients in Virginia, we identified a low rate of receipt of complete quality care for cervical cancer and a strong effect of facility volume on quality treatment and survival. Further research is needed to develop strategies to improve access to quality treatment and outcomes for cervical cancer. PMID:26937934

  10. Concomitant cervical and transperineal parametrial high-dose-rate brachytherapy boost for locally advanced cervical cancer

    PubMed Central

    Bailleux, Caroline; Falk, Alexander Tuan; Chand-Fouche, Marie-Eve; Gautier, Mathieu; Barranger, Emmanuel

    2016-01-01

    Purpose There is no consensus for parametrial boost technic while both transvaginal and transperineal approaches are discussed. A prototype was developed consisting of a perineal template, allowing transperineal needle insertion. This study analyzed acute toxicity of concomitant cervical and transperineal parametrial high-dose-rate brachytherapy (HDRB) boost for locally advanced cervical cancer. Material and methods From 01.2011 to 12.2014, 33 patients (pts) presenting a locally advanced cervical cancer with parametrial invasion were treated. After the first course of external beam radiation therapy with cisplatinum, HDRB was performed combining endocavitary and interstitial technique for cervical and parametrial disease. Post-operative delineation (CTV, bladder, rectum, sigmoid) and planification were based on CT-scan/MRI. HDRB was delivered in 3-5 fractions over 2-3 consecutive days. Acute toxicities occurring within 6 months after HDRB were retrospectively reviewed. Results Median age was 56.4 years (27-79). Clinical stages were: T2b = 23 pts (69.7%), T3a = 1 pt (3%), T3b = 6 pts (18.2%), and T4a = 3 pts (9.1%). Median HDRB prescribed dose was 21 Gy (21-27). Median CTVCT (16 pts) and HR-CTVMRI (17 pts) were 52.6 cc (28.5-74.3), 31.9 cc (17.1-58), respectively. Median EQD2αβ10 for D90CTV and D90HR-CTV were 82.9 Gy (78.2-96.5), 84.8 Gy (80.6-91.4), respectively. Median EQD2αβ3 (CT/MRI) for D2cc bladder, rectum and sigmoid were 75.5 Gy (66.6-90.9), 64.4 Gy (51.9-77.4), and 60.4 Gy (50.9-81.1), respectively. Median follow-up was 14 months (ranged 6-51). Among the 24 pts with MFU = 24 months, 2-year LRFS rate, RRFS, and OS were 86.8%, 88.8%, and 94.1%, respectively. The rates of acute genitourinary and gastrointestinal toxicities were 36% (G1 dysuria = 8 pts, G2 infection = 2 pts, G3 infection = 2 pts), and 27% (G1 diarrhea = 9 pts), respectively. One patient presented vaginal bleeding at the time of applicator withdrawal (G3-blood transfusion); no bleeding was

  11. A prospective study of the efficacy of magnetic resonance spectroscopy imaging for predicting locally advanced prostate cancer

    PubMed Central

    Razi, Ali; Parizi, Mehdi Kardoust; Kazemeini, Seid Mohammad; Abedi, Akbar

    2015-01-01

    Objective: To evaluate the efficacy of magnetic resonance spectroscopy imaging (MRSI) for predicting locally advanced prostate cancer (PC). Materials and methods: Between April 2009 and July 2012, 80 consecutive patients with clinically localized PC had undergone endorectal MRSI before radical retropubic prostatectomy. Clinicopathological parameters, including age, preoperative prostate-specific antigen (PSA), Gleason score (GS) at biopsy, perinural invasion at biopsy, prostate weight at surgery, GS of surgical specimen, and pathological staging were recorded. The MRSI findings were compared with the histopathological findings of the radical prostatectomy. The diagnostic accuracy measures consisting of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) of MRSI, and other variables in the diagnosis of locally advanced PC (Pathology Stages pT3a, pT3b, or pT4) were evaluated. Results: Sensitivity, specificity, PPV, and NPV of MRSI in detecting locally advanced PC is 42.4%, 93.6%, 82.3%, and 69.8%, respectively [area under the receiver operating characteristic (ROC) curve=0.658, p value <0.0001]. MRSI, cancer-positive core percentage at biopsy, and GS at biopsy are more accurate factors among all the predictive variables in predicting locally advanced PC. Conclusion: MRSI may be considered as a complementary diagnostic modality with high specificity and moderate sensitivity in predicting locally advanced PC. Combination of this modality with other predictive factors helps the surgeon and patient to select an appropriate treatment strategy. PMID:26328204

  12. Is It Possible to Shorten the Duration of Adjuvant Chemotherapy for Locally Advanced Rectal Cancer?

    PubMed Central

    You, Kai-Yun; Huang, Rong; Yu, Xin; Liu, Yi-Min; Gao, Yuan-Hong

    2016-01-01

    Abstract The long duration of 4 months of postoperative adjuvant chemotherapy is currently recommended for locally advanced rectal cancer after preoperative chemoradiation and surgery. Whether a short duration could be applied in these patients is unknown. So, the purpose of this study is to evaluate the effects on prognosis based on different durations of adjuvant chemotherapy for rectal cancer. We performed a retrospective study of 200 rectal cancer patients who were treated with preoperative chemoradiation and were pathologically graded as ypII and ypIII stages between March 2003 and May 2012. All patients were divided into 2 groups according to the median duration of adjuvant chemotherapy of 2 months. Overall survival (OS) and disease-free survival (DFS) were compared between patients with duration shorter and longer than 2 months in the whole group and subgroups of ypII and ypIII. Recurrence patterns were also analyzed in all subgroups. Multivariate analysis was performed to explore clinical factors that were significantly associated with DFS, local recurrence-free survival, and distant metastasis-free survival. In subgroup of ypII stage, the 5-year OS and DFS were similar between patients in long and short durations of adjuvant chemotherapy. For patients of ypIII stage, although no significant difference was found in OS between patients in short and long durations, DFS was showed to be higher in the group of long duration. Further analysis showed that longer duration of adjuvant chemotherapy could lead to improved control of distant metastasis and no impact on local control. Multivariable analysis indicated that long duration of adjuvant chemotherapy is significantly associated with longer distant metastasis-free survival in patients with ypIII stage, but not in those with ypII stage. A long duration of at least 2 months of postoperative adjuvant chemotherapy is necessary for patients with ypIII stage, whereas it may not be absolutely appropriate for those

  13. Predictive and prognostic biomarkers for neoadjuvant chemoradiotherapy in locally advanced rectal cancer.

    PubMed

    Lim, S H; Chua, W; Henderson, C; Ng, W; Shin, J-S; Chantrill, L; Asghari, R; Lee, C S; Spring, K J; de Souza, P

    2015-10-01

    Locally advanced rectal cancer is regularly treated with trimodality therapy consisting of neoadjuvant chemoradiation, surgery and adjuvant chemotherapy. There is a need for biomarkers to assess treatment response, and aid in stratification of patient risk to adapt and personalise components of the therapy. Currently, pathological stage and tumour regression grade are used to assess response. Experimental markers include proteins involved in cell proliferation, apoptosis, angiogenesis, the epithelial to mesenchymal transition and microsatellite instability. As yet, no single marker is sufficiently robust to have clinical utility. Microarrays that screen a tumour for multiple promising candidate markers, gene expression and microRNA profiling will likely have higher yield and it is expected that a combination or panel of markers would prove most useful. Moving forward, utilising serial samples of circulating tumour cells or circulating nucleic acids can potentially allow us to demonstrate tumour heterogeneity, document mutational changes and subsequently measure treatment response. PMID:26032919

  14. Systematic review of novel ablative methods in locally advanced pancreatic cancer

    PubMed Central

    Keane, Margaret G; Bramis, Konstantinos; Pereira, Stephen P; Fusai, Giuseppe K

    2014-01-01

    Unresectable locally advanced pancreatic cancer with or without metastatic disease is associated with a very poor prognosis. Current standard therapy is limited to chemotherapy or chemoradiotherapy. Few regimens have been shown to have a substantial survival advantage and novel treatment strategies are urgently needed. Thermal and laser based ablative techniques are widely used in many solid organ malignancies. Initial studies in the pancreas were associated with significant morbidity and mortality, which limited widespread adoption. Modifications to the various applications, in particular combining the techniques with high quality imaging such as computed tomography and intraoperative or endoscopic ultrasound has enabled real time treatment monitoring and significant improvements in safety. We conducted a systematic review of the literature up to October 2013. Initial studies suggest that ablative therapies may confer an additional survival benefit over best supportive care but randomised studies are required to validate these findings. PMID:24605026

  15. Nonsurgical Management of Cervical Cancer: Locally Advanced, Recurrent, and Metastatic Disease, Survivorship, and Beyond

    PubMed Central

    Mackay, Helen J.; Wenzel, Lari; Mileshkin, Linda

    2016-01-01

    Overview Despite the declining incidence of cervical cancer as a result of the introduction of screening programs, globally it remains a leading cause of cancer-related death in women. Outcomes for patients who are diagnosed with anything but early-stage disease remain poor. Here we examine emerging strategies to improve the treatment of locally advanced disease. We discuss emerging biologic data, which are informing our investigation of new therapeutic interventions in persistent, recurrent, and metastatic cervical cancer. We recognize the importance of interventions to improve quality of life and to prevent long-term sequelae in women undergoing treatment. Finally, and perhaps most importantly, we recognize the need for global collaboration and advocacy to improve the outcome for all women at risk of and diagnosed with this disease. PMID:25993189

  16. High intensity focused ultrasound: A noninvasive therapy for locally advanced pancreatic cancer

    PubMed Central

    Wu, Feng

    2014-01-01

    The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound (HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer. PMID:25469016

  17. Managing locally advanced prostate cancer: a urologist's and a patient's perspective.

    PubMed

    Kirby, Roger; Offen, Nigel

    2006-03-01

    A 60-year-old man presented to his general practitioner with prostatic symptoms and high blood pressure. Based upon a prostate-specific antigen level of 44 ng/ml and further investigations (digital rectal examination, transrectal ultrasound-guided needle biopsy, and magnetic resonance imaging, ultrasound and bone scans), the patient was diagnosed with locally advanced (cT3, N0, M0) prostate cancer. Here, the urologist and the patient describe treatment from their respective viewpoints. Following discussion of the advantages and disadvantages of the various therapeutic options, radiotherapy plus hormonal therapy (bicalutamide 150 mg) was chosen as the approach that best suited the patient's lifestyle. In this review, the patient and the urologist consider the impact of the chosen treatment in terms of efficacy, tolerability and quality of life. PMID:16520652

  18. PELVIC ACTINOMYCOSIS MIMICKING A LOCALLY ADVANCED PELVIC MALIGNANCY--CASE REPORT.

    PubMed

    Velenciuc, Natalia; Velenciuc, I; Makkai Popa, S; Roată, C; Ferariu, D; Luncă, S

    2016-01-01

    We present the case of a former user of an intrauterine contraceptive device (IUD) for 10 years, diagnosed with a bulky, fixed pelvic tumor involving the internal genital organs and the recto sigmoid, causing luminal narrowing of the rectum, interpreted as locally advanced pelvic malignancy, probably of genital origin. Intraoperatively, a high index of suspicion made us collect a sample from the fibrous wall of the tumor mass, large Actinomyces colonies were thus identified. Surgery consisted in debridement, removal of a small amount of pus and appendectomy, thus avoiding a mutilating and useless surgery. Specific antibiotic therapy was administered for 3 months, with favorable postoperative and long-term outcomes. Pelvic actinomycosis should always be considered in the differential diagnosis of pelvic tumors in women using an IUD. The association of long-term antibiotic treatment is essential to eradicate the infection and prevent relapses. PMID:27483724

  19. New Strategies for Multimodality Therapy in Treating Locally Advanced Cervix Cancer.

    PubMed

    Verma, Jonathan; Monk, Bradley J; Wolfson, Aaron H

    2016-10-01

    Cervical cancer is the fourth most common cause of cancer of women worldwide. In the developing world, it comprises 12% of all cancers of women. Since 1999, the mainstay of treatment for locally advanced cervical cancer (LACC) has been concurrent cisplatin-based chemoradiation. However, outcomes in this disease remain suboptimal, with long-term progression-free survival and overall survival rates of approximately 60%. There are several new strategies of combined modality treatment under evaluation in LACC, including chemotherapy before and after treatment as well as novel agents such as poly-adenosine diphosphate ribose polymerase inhibitors, antiangiogenic blockage, and immunotherapy. We provide a brief overview of these strategies and their potential in the treatment of women with LACC. PMID:27619255

  20. Telescope performance near local midnight for the Japanese Advanced Meteorological Imager (JAMI)

    NASA Astrophysics Data System (ADS)

    Pavlov, Milutin M.; Bell, James L., Jr.; Hurt, W. Todd; Jacoby, Michael; Shreckengost, Belinda; Ravela, Russ; Schwarz, Mark A.

    2005-01-01

    Raytheon's Santa Barbara Remote Sensing (SBRS) division designed and built the MTSAT-1R Japanese Advanced Meteorological Imager for the Japanese Ministry of Transport between March, 1999 and July, 2002. In order to meet the stressing requirements of a geosynchronous orbit, a combination of structural, thermal, and optical (STOP) analyses were used to design and optimize the beryllium three-mirror anastigmat (TMA) telescope. This modeling approach was used to characterize and minimize the thermal distortion around local midnight. On-orbit temperatures and structural deformations were predicted using thermal Desktop/SINDA and PATRAN/NASTRAN software, respectively. The resulting optical performance was evaluated using Raytheon developed HEXAGON software. The telescope design was successfully optimized to attain specified visible channel performance for most of the 24 hour orbit.

  1. High intensity focused ultrasound: a noninvasive therapy for locally advanced pancreatic cancer.

    PubMed

    Wu, Feng

    2014-11-28

    The noninvasive ablation of pancreatic cancer with high intensity focused ultrasound (HIFU) energy is received increasingly widespread interest. With rapidly temperature rise to cytotoxic levels within the focal volume of ultrasound beams, HIFU can selectively ablate a targeted lesion of the pancreas without any damage to surrounding or overlying tissues. Preliminary studies suggest that this approach is technical safe and feasible, and can be used alone or in combination with systemic chemotherapy for the treatment of patients with locally advanced pancreatic cancer. It can effectively alleviate cancer-related abdominal pain, and may confer an additional survival benefit with few significant complications. This review provides a brief overview of HIFU, describes current clinical applications, summarizes characteristics of continuous and pulsed HIFU, and discusses future applications and challenges in the treatment of pancreatic cancer. PMID:25469016

  2. Capecitabine-induced leukocytoclastic vasculitis under neoadjuvant chemotherapy for locally advanced colorectal cancer

    PubMed Central

    Kee, Bryan K.; Tetzlaff, Michael T.; Wolff, Robert A.

    2015-01-01

    We describe a case of capecitabine-induced leukocytoclastic vasculitis in a patient with locally advanced rectal cancer under curative neoadjuvant concurrent chemoradiation using capecitabine. After 5 days of the initiation of capecitabine the patient developed a pruritic maculopapular rash in her extremities consistent with vasculitis which was confirmed on skin biopsy without any signs of systemic involvement. Capecitabine was held and the rash was treated with topical steroids with complete resolution of both rash and pruritus. Due to a lack of other alternative chemotherapeutic options and the cutaneous-only involvement of vasculitis, the capecitabine was re-introduced. Two days later, the patient developed an identical maculopapular rash with a similar distribution. Prednisone was initiated while the capecitabine was continued with complete resolution of the rash. The patient successfully completed her curative neoadjuvant chemoradiation therapy treatment without the need to permanently discontinue the capecitabine. PMID:26029464

  3. Intraoperative Radiotherapy Combined With Adjuvant Chemoradiotherapy for Locally Advanced Gastric Adenocarcinoma

    SciTech Connect

    Fu Shen; Lu Jiade; Zhang Qing Yang Zhe; Peng Lihua; Xiong, Fei

    2008-12-01

    Purpose: To evaluate the efficacy of intraoperative radiotherapy (IORT) followed by concurrent chemotherapy and external beam RT (EBRT) in the treatment of locally advanced gastric adenocarcinoma. Methods and Materials: A total of 97 consecutive and nonselected patients with newly diagnosed Stage T3, T4, or N+ adenocarcinoma of the stomach underwent gastrectomy with D2 lymph node dissection between March 2003 and October 2005. Of the 97 patients, 51 received adjuvant concurrent chemotherapy (5-fluorouracil, leucovorin, docetaxel, and cisplatin) and EBRT (EBRT group) and 46 received IORT (dose range, 12-15 Gy) immediately after gastrectomy and lymph node dissection before concurrent chemoradiotherapy (EBRT+IORT group). Results: After a median follow-up of 24 months, the 3-year locoregional control rate was 77% and 63% in the two groups with or without IORT, respectively (p = 0.05). The 3-year overall survival and disease-free survival rate was 47% and 36% in the EBRT group and 56% and 44% in the EBRT+IORT group, respectively (p > 0.05). Multivariate analyses revealed that the use of IORT, presence of residual disease after surgery, and pN category were independent prognostic factors for locoregional control and that IORT, pN, and pT categories were independent prognostic factors for overall survival (p < 0.05). Four patients experienced Grade 3 or 4 late complications, but no significant difference was observed between the two groups. Conclusions: Radical gastrectomy with D2 lymph node dissection and IORT followed by adjuvant chemoradiotherapy appeared to be feasible and well-tolerated in the treatment of locally advanced gastric cancer. The addition of IORT to the trimodality treatment significantly improved the 3-year locoregional control rate.

  4. Comparison of 5-fluorouracil/leucovorin and capecitabine in preoperative chemoradiotherapy for locally advanced rectal cancer

    SciTech Connect

    Kim, Dae Yong; Jung, Kyung Hae . E-mail: khjung@ncc.re.kr; Kim, Tae Hyun; Kim, Duck-Woo; Chang, Hee Jin; Jeong, Jun Yong; Kim, Young Hoon; Son, Seok-Hyun; Yun, Tak; Hong, Chang Won; Sohn, Dae Kyung; Lim, Seok-Byung; Choi, Hyo Seong; Jeong, Seung-Yong; Park, Jae-Gahb

    2007-02-01

    Purpose: To describe our experience with a bolus injection of 5-fluorouracil and leucovorin (FL) vs. capecitabine in terms of radiologic and pathologic findings in preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer. Methods: The study enrolled 278 patients scheduled for preoperative CRT using two protocols with different chemotherapeutic regimens. Pelvic radiotherapy (50.4 Gy) was delivered concurrently with FL (n = 145) or capecitabine (n = 133). Surgery was performed 6 weeks after CRT completion. Tumor responses to CRT were measured using both radiologic and pathologic examination. Magnetic resonance volumetry was performed at the initial workup and just before surgery after completion of preoperative CRT. Post-CRT pathology tests were used to determine tumor stage and regression. Results: Radiologic examination showed that tumor volume decreased by 68.2% {+-} 20.5% in the FL group and 68.3% {+-} 22.3% in the capecitabine group (p = 0.970). Postoperative pathologic T stage determination showed that downstaging occurred in 44.3% of FL and 49.9% of capecitabine patients (p = 0.571). The tumor regression grades after CRT were Grade 1 (minimal response) in 22.6% and 21.0%, Grade 2 (moderate response) in 53.2% and 50.0%, Grade 3 (near-complete response) in 12.9% and 12.9%, and Grade 4 (complete response) in 11.3% and 16.1% of the FL and capecitabine groups, respectively (p = 0.758). Conclusion: In the present study, the radiologic and pathologic findings did not reveal significant differences in short-term tumor responses between preoperative FL and capecitabine CRT for locally advanced rectal cancer. Long-term results and a prospective randomized trial are needed.

  5. Cervical brachytherapy technique for locally advanced carcinoma of the cervix in a patient with septate uterus

    PubMed Central

    Wallace, Charlie; Gondi, Vinai; Das, Rupak; Straub, Margaret; Al-Niaimi, Ahmed; Applegate, Glenn; Bradley, Kristin A.

    2014-01-01

    Purpose To describe an approach to cervical brachytherapy in a patient with congenital septate uterus and locally advanced cervical carcinoma. Material and methods The patient is a 34-year-old female with septate uterus presenting with pelvic pain. Workup demonstrated a stage IIB cervical adenocarcinoma with imaging evidence of an involved right external iliac lymph node. The patient received whole pelvic radiation, with concurrent weekly cisplatin (40 mg/m2), to a dose of 45 Gy in 25 fractions followed by a parametrial boost of 5.4 Gy and an additional nodal boost of 9 Gy. Results The patient was initiated on cervical brachytherapy following fraction 23 of pelvic radiation. To conform to her septated uterus, a Rotte-Y tandem was used. Additionally, 2 CT-compatible ovoids were placed in the vaginal apex to enhance dose distribution and coverage of the target volume. Each fraction of brachytherapy was performed with CT-based planning. A high-risk clinical target volume (HR-CTV) and normal structures were defined and constrained per American Brachytherapy Society (ABS) and Groupe Européen de Curiethérapie/European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) guidelines. The brachytherapy dose was 27.5 Gy in 5 fractions of 5.5 Gy each, prescribed to the HR-CTV. Conclusions Herein, we report the first documented case of cervical brachytherapy in a patient with septate uterus and locally advanced cervical carcinoma. Using CT-guided planning, in conjunction with the ABS and GEC-ESTRO guidelines, the patient was effectively treated with adapted cervical brachytherapy, meeting criteria for HR-CTV coverage and normal tissue tolerances. PMID:24790625

  6. Radiotherapy Technical Considerations in the Management of Locally Advanced Pancreatic Cancer: American-French Consensus Recommendations

    SciTech Connect

    Huguet, Florence; Goodman, Karyn A.; Azria, David; Racadot, Severine; Abrams, Ross A.

    2012-08-01

    Summary: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose

  7. Treatment of Locally Advanced Adenoid Cystic Carcinoma of the Trachea With Neutron Radiotherapy

    SciTech Connect

    Bittner, Nathan; Koh, W.-J.; Laramore, George E.; Patel, Shilpen; Mulligan, Michael S.; Douglas, James G.

    2008-10-01

    Purpose: To examine the efficacy of fast neutron radiotherapy in the treatment of locally advanced adenoid cystic carcinoma (ACC) of the trachea and to compare outcomes with and without high-dose-rate (HDR) endobronchial brachytherapy boost. Methods and Materials: Between 1989 and 2005, a total of 20 patients with ACC of the trachea were treated with fast neutron radiotherapy at University of Washington. Of these 20 patients, 19 were treated with curative intent. Neutron doses ranged from 10.7 to 19.95 Gy (median, 19.2 Gy). Six of these patients received an endobronchial brachytherapy boost using an HDR {sup 192}Ir source (3.5 Gy x 2 fractions). Median duration of follow-up was 46 months (range, 10-121 months). Results: The 5-year actuarial overall survival rate and median overall survival for the entire cohort were 89.4%, and 97 months, respectively. Overall survival was not statistically different among those patients receiving an endobronchial boost compared with those receiving neutron radiotherapy alone (100% vs. 68%, p = 0.36). The 5-year actuarial locoregional control rate for the entire cohort was 54.1%. The locoregional control rate was not statistically different among patients who received an endobronchial boost compared with those who received neutron radiotherapy alone (40% vs. 58%, p 0.94). There were no cases of Grade {>=}3 acute toxicity. There were 2 cases of Grade 3/4 chronic toxicity. Conclusions: Fast neutron radiotherapy is an effective treatment for locally advanced adenoid cystic carcinoma of the trachea, with acceptable treatment-related toxicity.

  8. Dose escalation with stereotactic body radiation therapy boost for locally advanced non small cell lung cancer

    PubMed Central

    2013-01-01

    Introduction Low survival outcomes have been reported for the treatment of locally advanced non small cell lung cancer (LA-NSCLC) with the standard of care treatment of concurrent chemoradiation (cCRT). We present our experience of dose escalation using stereotactic body radiosurgery (SBRT) following conventional cCRT for patients with LA-NSCLC. Methods Sixteen patients with a median age of 67.5 treated with fractionated SBRT from 2010 to 2012 were retrospectively analyzed. Nine (56%) of the patients had stage IIIB, 6 (38%) has stage IIIA, and 1 (6%) had recurrent disease. Majority of the patients (63%) presented with N2 disease. All patients had a PET CT for treatment planning. Patients received conventional cCRT to a median dose of 50.40 Gy (range 45–60) followed by an SBRT boost with an average dose of 25 Gy (range 20–30) given over 5 fractions. Results With a median follow-up of 14 months (range, 1–14 months), 1-year overall survival (OS), progression free survival (PFS), local control (LC), regional control (RC), and distant control (DC) rates were, 78%, 42%, 76%, 79%, and 71%, respectively. Median times to disease progression and regional failure were 10 months and 18 months, respectively. On univariate analysis, advanced age and nodal status were worse prognostic factors of PFS (p < 0.05). Four patients developed radiation pneumonitis and one developed hemoptysis. Treatment was interrupted in one patient who required hospitalization due to arrhythmias and pneumonia. Conclusion Risk adaptive dose escalation with SBRT following external beam radiotherapy is possible and generally tolerated treatment option for patients with LA-NSCLC. PMID:23842112

  9. The Quality-of-Life Effects of Neoadjuvant Chemoradiation in Locally Advanced Rectal Cancer

    SciTech Connect

    Herman, Joseph M.; Narang, Amol K.; Griffith, Kent A.; Zalupski, Mark M.; Reese, Jennifer B.; Gearhart, Susan L.; Azad, Nolifer S.; Chan, June; Olsen, Leah; Efron, Jonathan E.; Lawrence, Theodore S.; Ben-Josef, Edgar

    2013-01-01

    Purpose: Existing studies that examine the effect of neoadjuvant chemoradiation (CRT) for locally advanced rectal cancer on patient quality of life (QOL) are limited. Our goals were to prospectively explore acute changes in patient-reported QOL endpoints during and after treatment and to establish a distribution of scores that could be used for comparison as new treatment modalities emerge. Methods and Materials: Fifty patients with locally advanced rectal cancer were prospectively enrolled at 2 institutions. Validated cancer-specific European Organization for Research and Treatment of Cancer (EORTC QLQ-CR30) and colorectal cancer-specific (EORTC QLQ-CR38 and EORTC QLQ-CR 29) QOL questionnaires were administered to patients 1 month before they began CRT, at week 4 of CRT, and 1 month after they had finished CRT. The questionnaires included multiple symptom scales, functional domains, and a composite global QOL score. Additionally, a toxicity scale was completed by providers 1 month before the beginning of CRT, weekly during treatment, and 1 month after the end of CRT. Results: Global QOL showed a statistically significant and borderline clinically significant decrease during CRT (-9.50, P=.0024) but returned to baseline 1 month after the end of treatment (-0.33, P=.9205). Symptoms during treatment were mostly gastrointestinal (nausea/vomiting +9.94, P<.0001; and diarrhea +16.67, P=.0022), urinary (dysuria +13.33, P<.0001; and frequency +11.82, P=.0006) or fatigue (+16.22, P<.0001). These symptoms returned to baseline after therapy. However, sexual enjoyment (P=.0236) and sexual function (P=.0047) remained persistently diminished after therapy. Conclusions: Rectal cancer patients undergoing neoadjuvant CRT may experience a reduction in global QOL along with significant gastrointestinal and genitourinary symptoms during treatment. Moreover, provider-rated toxicity scales may not fully capture this decrease in patient-reported QOL. Although most symptoms are transient

  10. Utility of Rectoscopy in the Assessment of Response to Neoadjuvant Treatment for Locally Advanced Rectal Cancer

    PubMed Central

    Lopez-Lopez, Victor; Abrisqueta, Jesús; Lujan, Juán; Hernández, Quiteria; Ono, Akiko; Parrilla, Pascual

    2016-01-01

    Background/Aims: The management of locally advanced rectal cancer has changed substantially over the last few decades with neoadjuvant chemoradiotherapy. The aim of the present study is to compare the results between neoadjuvant post-treatment rectoscopy and the anatomopathological findings of the surgical specimen. Patients and Methods: We conducted a prospective study of 67 patients with locally advanced adenocarcinoma of the rectum (stages II and III). Two groups were established: One with complete clinical response (cCR) and one without (non-cCR), based on the findings at rectoscopy. Assessment of tumor regression grade in the surgical specimen was determined using Mandard's tumor regression scale. Results: Seventeen patients showed a cCR. Thirty-five biopsies were negative and 32 were positive for mailgnancy. All the cCR patients had a negative biopsy (P < 0.0001). All 32 positive biopsies revealed the presence of adenocarcinoma, and of the 35 negative biopsies, 18 had no malignancy and 17 were diagnosed with adenocarcinoma (P < 0.0001). Sixteen of the 17 cCR patients showed a complete pathological response and one patient showed the presence of adenocarcinoma. Of the 50 non-cCR patients 48 revealed the presence of adenocarcinoma and two had absence of malignancy. According to the Mandard classification, 16 of the 17 cCR patients were grade I and 1 grade II; 2 non-cCR patients were grade I, 7 grade II, 13 grade III, 19 grade IV, and 9 grade V. Conclusions: Endoscopic and histological findings could be determinants in the assessment of response to neoadjuvant treatment. PMID:26997222

  11. Adjuvant role of radiation therapy for locally advanced laryngeal cancer without pathological lymph node metastasis.

    PubMed

    Kim, Sung Hee; Lee, Yoon Se; Kwon, Minsu; Kim, Ji Won; Roh, Jong-Lyel; Choi, Seung-Ho; Kim, Sang Yoon; Lee, Sang-Wook; Nam, Soon Yuhl

    2016-07-01

    Conclusion The application of adjuvant RT to reduce recurrence should be tailored in cases of pathologically negative node metastasis. Objectives The treatment modality following surgical resection of advanced laryngeal cancer is determined by adverse factors. Aside from lymph node metastasis (LNM) or positive margins, definite risk factors supporting adjuvant radiation therapy (RT) have not been clearly suggested. The aim of this study was to analyze the risk factors for advanced laryngeal cancer without LNM and the role of RT. Materials and methods Pathologically T3 and T4-staged laryngeal squamous cell carcinoma without LNM were reviewed. The patients were classified into RT (+) (n = 22) and RT (-) (n = 38) groups. Results Five-year overall survival (OS) of the RT (+) and RT (-) groups was 84.4% and 83.8%, respectively. Five-year disease-specific survival of the RT (+) and RT (-) groups was 88.4% and 93.9%. Five-year local control rate of the RT (+) and RT (-) groups was 94.7% and 91.3%. The factors affecting OS were smoking history and recurrence history (p = 0.02). By multivariate analysis, smoking history and recurrence history were determining factors for 5-year OS (p = 0.024 and p = 0.047, respectively). PMID:26924463

  12. Epigenomic Characterization of Locally Advanced Anal Cancer: An RTOG 98-11 Specimen Study

    PubMed Central

    Siegel, Erin M; Eschrich, Steven; Winter, Kathryn; Riggs, Bridget; Berglund, Anders; Ajidahun, Abidemi; Simko, Jeff; Moughan, Jennifer; Ajani, Jaffer; Magliocco, Anthony; Elahi, Abul; Hoffe, Sarah; Shibata, David

    2014-01-01

    Background The Radiation Therapy Oncology Group 98-11 clinical trial demonstrated the superiority of standard 5FU/mitomycin-C over 5FU/cisplatin in combination with radiation in the treatment of anal squamous cell cancer. Tumor size (>5cm) and lymph node metastases are associated with disease progression. There may be key molecular differences (e.g. DNA methylation changes) in tumors at high-risk for progression. Objectives The objectives of this study were to determine if there are differences in DNA methylation at individual CpG sites and within genes among locally advanced anal cancers, with large tumor size and/or nodal involvement, compared to those that are less advanced. Design Case-case study among 121 patients defined as high-risk (tumor size>5cm and/or nodal involvement; n=59) or low-risk (≤5cm, node negative; n=62) within the mitomycin-C arm of RTOG98-11 trial. DNA methylation was measured using the Illumina HumanMethylation450 Array. Settings Tertiary care cancer center in collaboration with a national clinical trials cooperative group. Patients The patients consisted of 74 women and 47 men with a median age of 54 years (minmax 25-79). Main Outcome Measures DNA methylation differences at individual CpG sites and within genes between low and high-risk patients were compared using Mann-Whitney test (p-value<0.001). Results A total of 16 CpG loci were differentially methylated (14 increased and 2 decreased) in high vs. low-risk cases. Genes harboring differentially methylated CpG sites included known tumor suppressor genes and novel targets. Limitations This study only included patients in mitomycin-C arm with tumor tissue; however, this sample was representative of the trial. Conclusions This is the first study to apply genome-wide methylation analysis to anal cancer. Biologically relevant differences in methylated targets were found to discriminate locally advanced from early anal cancer. Epigenetic events likely play a significant role in the

  13. [Management of locally advanced anal canal carcinoma with modulated arctherapy and concurrent chemotherapy].

    PubMed

    Troussier, I; Huguet, F; Servagi-Vernat, S; Benahim, C; Khalifa, J; Darmon, I; Ortholan, C; Krebs, L; Dejean, C; Fenoglietto, P; Vieillot, S; Bensadoun, R-J; Thariat, J

    2015-04-01

    The standard treatment of locally advanced (stage II and III) squamous cell carcinoma of the anal canal consists of concurrent chemoradiotherapy (two cycles of 5-fluoro-uracil, mitomycin C, on a 28-day cycle), with a dose of 45 Gy in 1.8 Gy per fraction in the prophylactic planning target volume and additional 14 to 20 Gy in the boost planning target volume (5 days per week) with a possibility of 15 days gap period between the two sequences. While conformal irradiation may only yield suboptimal tumor coverage using complex photon/electron field junctions (especially on nodal areas), intensity modulated radiation therapy techniques (segmented static, dynamic, volumetric modulated arc therapy and helical tomotherapy) allow better tumour coverage while sparing organs at risk from intermediate/high doses (small intestine, perineum/genitalia, bladder, pelvic bone, etc.). Such dosimetric advantages result in fewer severe acute toxicities and better potential to avoid a prolonged treatment break that increases risk of local failure. These techniques also allow a reduction in late gastrointestinal and skin toxicities of grade 3 or above, as well as better functional conservation of anorectal sphincter. The technical achievements (simulation, contouring, prescription dose, treatment planning, control quality) of volumetric modulated arctherapy are discussed. PMID:25770884

  14. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

    SciTech Connect

    Schaake-Koning, C.; van der Linden, E.H.; Hart, G.; Engelsman, E.

    1985-10-01

    Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.

  15. CT Findings of Patients Treated with Irreversible Electroporation for Locally Advanced Pancreatic Cancer.

    PubMed

    Akinwande, Olaguoke; Ahmad, Shakeeb S; Van Meter, Tracy; Schulz, Brittany; Martin, Robert C G

    2015-01-01

    Introduction. In patients with locally advanced pancreatic cancer (LAPC), IRE has been shown to be safe for local disease control and palliation. As IRE continues to gain acceptance it is important to characterize the expected imaging findings. Materials and Methods. A review of our prospective soft tissue ablation registry from July 2010 to June 2013 was performed on patients who had undergone IRE for LAPC. Five masses treated with intraoperative IRE ablation for pancreatic tumors that underwent CT imaging before and after ablation were reviewed. Results and Discussion. Following IRE, the postablation bed is larger than the original ablated tumor. This ablation zone may get smaller in size (due to decreased edema and hyperemia) in the following months and more importantly remains stable provided there is no recurrence. In cases of recurrent disease there is increased size of the ablation bed, mass effect, and new or worsening vascular encasement or occlusion. Conclusion. CT imaging remains the best current imaging modality to assess post-IRE ablation changes. Serial imaging over at least 2-6 months must be employed to detect recurrence by comparing with prior studies in conjunction with clinical and serum studies. Larger imaging studies are underway to evaluate a more ideal imaging modality for this unique patient population. PMID:26649039

  16. Analysis of clinical efficacy of CyberKnife® treatment for locally advanced pancreatic cancer

    PubMed Central

    Song, Yongchun; Yuan, Zhiyong; Li, Fengtong; Dong, Yang; Zhuang, Hongqing; Wang, Jingsheng; Chen, Huaming; Wang, Ping

    2015-01-01

    Objective To evaluate the efficacy and safety of CyberKnife® treatment for locally-advanced pancreatic cancer (LAPC). Methods The efficacy of CyberKnife® treatment was analyzed in 59 LAPC patients treated between October 2006 and September 2014. The median tumor volume was 27.1 mL (13.0–125.145 mL). The median prescribed dose was 45 Gy (35–50 Gy), delivered in 5 fractions (3–8 fractions). The overall survival (OS) rates and freedom from local progression (FFLP) rates were estimated using the Kaplan–Meier survival curve. Results The median follow-up for all patients was 10.9 months (3.2–48.7 months) and 15.6 months (3.9–37.6 months) among surviving patients. The median OS was 12.5 months, and the 1-year and 2-year survival rates were 53.9% and 35.1%, respectively. The 1-year FFLP rate was 90.8% based on the computed tomography (CT) evaluation. Grade 1–2 acute and late-stage gastrointestinal (GI) reactions were observed in 61% of the patients. One patient experienced grade 3 toxicity. Conclusion Excellent clinical efficacy was obtained after treatment of LAPC using CyberKnife®, with minimal toxicity. PMID:26109866

  17. Management of inferior vena cava tumor thrombus in locally advanced renal cell carcinoma

    PubMed Central

    Psutka, Sarah P.

    2015-01-01

    The diagnosis of renal cell carcinoma is accompanied by intravascular tumor thrombus in up to 10% of cases, of which nearly one-third of patients also have concurrent metastatic disease. Surgical resection in the form of radical nephrectomy and caval thrombectomy represents the only option to obtain local control of the disease and is associated with durable oncologic control in approximately half of these patients. The objective of this clinical review is to outline the preoperative evaluation for, and operative management of patients with locally advanced renal cell carcinoma with venous tumor thrombi involving the inferior vena cava. Cornerstones of the management of these complex patients include obtaining high-quality imaging to characterize the renal mass and tumor thrombus preoperatively, with further intraoperative real-time evaluation using transesophageal echocardiography, careful surgical planning, and a multidisciplinary approach. Operative management of patients with high-level caval thrombi should be undertaken in high-volume centers by surgical teams with capacity for bypass and invasive intraoperative monitoring. In patients with metastatic disease at presentation, cytoreductive nephrectomy and tumor thrombectomy may be safely performed with simultaneous metastasectomy if possible. In the absence of level one evidence, neoadjuvant targeted therapy should continue to be viewed as experimental and should be employed under the auspices of a clinical trial. However, in patients with significant risk factors for postoperative complications and mortality, and especially in those with metastatic disease, consultation with medical oncology and frontline targeted therapy may be considered. PMID:26445601

  18. Alternative Response Criteria (Choi, European Association for the Study of the Liver, and Modified Response Evaluation Criteria in Solid Tumors [RECIST]) Versus RECIST 1.1 in Patients With Advanced Hepatocellular Carcinoma Treated With Sorafenib

    PubMed Central

    Ronot, Maxime; Bouattour, Mohamed; Wassermann, Johanna; Bruno, Onorina; Dreyer, Chantal; Larroque, Béatrice; Castera, Laurent; Vilgrain, Valérie; Belghiti, Jacques; Raymond, Eric

    2014-01-01

    Introduction. Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), may underestimate activity and does not predict survival in patients with hepatocellular carcinoma (HCC) treated with sorafenib. This study assessed the value of alternative radiological criteria to evaluate response in HCC patients treated with sorafenib. Patients and Methods. A retrospective blinded central analysis was performed of computed tomography (CT) scans from baseline and the first tumor evaluation in consecutive patients treated with sorafenib over a 2-year period in a single institution. Four different evaluation criteria were used: Choi, European Association for the Study of the Liver (EASL), modified RECIST (mRECIST), and RECIST 1.1. Results. Among 82 HCC patients, 64 with Barcelona Clinic Liver Cancer stage B-C were evaluable with a median follow-up of 22 months. Median duration of sorafenib treatment was 5.7 months, and median overall survival was 12.8 months. At the time of the first CT scan, performed after a median of 2.1 months, Choi, EASL, mRECIST, and RECIST 1.1 identified 51%, 28%, 28%, and 3% objective responses, respectively. Responders by all criteria showed consistent overall survival >20 months. Among patients with stable disease according to RECIST 1.1, those identified as responders by Choi had significantly better overall survival than Choi nonresponders (22.4 vs. 10.6 months; hazard ratio: 0.43, 95% confidence interval: 0.15–0.86, p = .0097). Conclusion. Choi, EASL, and mRECIST criteria appear more appropriate than RECIST 1.1 to identify responders with long survival among advanced HCC patients benefiting from sorafenib. PMID:24652387

  19. Locally Advanced Prostate Cancer: Three-Dimensional Magnetic Resonance Spectroscopy to Monitor Prostate Response to Therapy

    SciTech Connect

    Valentini, Anna Lia; Gui, Benedetta; D'Agostino, Giuseppe Roberto; Mattiucci, Giancarlo; Clementi, Valeria; Di Molfetta, Ippolita Valentina; Bonomo, Pierluigi; Mantini, Giovanna

    2012-11-01

    Purpose: To correlate results of three-dimensional magnetic resonance spectroscopic imaging (MRSI) with prostate-specific antigen (PSA) levels and time since external beam irradiation (EBRT) in patients treated with long-term hormone therapy (HT) and EBRT for locally advanced disease to verify successful treatment by documenting the achievement of metabolic atrophy (MA). Methods and Materials: Between 2006 and 2008, 109 patients were consecutively enrolled. MA was assessed by choline and citrate peak area-to-noise-ratio <5:1. Cancerous metabolism (CM) was defined by choline-to-creatine ratio >1.5:1 or choline signal-to-noise-ratio >5:1. To test the strength of association between MRSI results and the time elapsed since EBRT (TEFRT), PSA levels, Gleason score (GS), and stage, logistic regression (LR) was performed. p value <0.05 was statistically significant. The patients' outcomes were verified in 2011. Results: MRSI documented MA in 84 of 109 and CM in 25 of 109 cases. LR showed that age, GS, stage, and initial and recent PSA had no significant impact on MRSI results which were significantly related to PSA values at the time of MRSI and to TEFRT. Patients were divided into three groups according to TEFRT: <1 year, 1-2 years, and >2 years. MA was detected in 54.1% of patients of group 1, 88.9% of group 2, and in 94.5% of group 3 (100% when PSA nadir was reached). CM was detected in 50% of patients with reached PSA nadir in group 1. Local relapse was found in 3 patients previously showing CM at long TEFRT. Conclusion: MA detection, indicative of successful treatment because growth of normal or abnormal cells cannot occur without metabolism, increases with decreasing PSA levels and increasing time on HT after EBRT. This supports long-term HT in advanced prostate cancer. Larger study series are needed to assess whether MRSI could predict local relapse by detecting CM at long TEFRT.

  20. Current approach in the treatment of hepatocellular carcinoma

    PubMed Central

    Rossi, Luigi; Zoratto, Federica; Papa, Anselmo; Iodice, Francesca; Minozzi, Marina; Frati, Luigi; Tomao, Silverio

    2010-01-01

    Hepatocellular carcinoma (HCC) is the most common malignant hepatobiliary disease; it is responsible for about 1 million deaths per year. Risk factors include hepatitis B and C, hepatic cirrhosis, including alcohol related hepatitis, metabolic and nutritional hepatic damage. The main modality of diffusion is intrahepatic in the natural course of the disease. There are two leading types of treatment: local and systemic. Surgical resection and liver transplantation constitute the most appropriate local treatments and are considered the only real possibility for recovery. Other local approaches include: radiofrequency ablation, percutaneous ethanol ablation, hepatic endoarterial chemoembolization and intrahepatic radiotherapy (SIRT: selective internal radiation therapy). These last treatments are used to control the disease when surgery or transplantation is not achievable; in some cases they are able to prolong survival while they constitute mainly a palliative treatment. Systemic treatments include: chemotherapy, immunological and hormonal therapies and, more recently, the introduction of new specific molecular target drugs. At the moment, in this group, the only drug that has given positive results during phase III trials (SHARP study) is Sorafenib. Sorafenib represents the only primary systemic therapy that has demonstrated, unlike the other treatments previously described, an increase in survival rate in patients affected with advanced HCC. Currently, other studies are taking place that are further developing the potential of this drug. These studies, including phase III trials, are directed in order to test the activity and safety of new emerging drugs with targeted activity. Examples of these new agents are: Sunitinib, Gefitinib, Cetuximab, Bevacizumab and Erlotinib. PMID:21160806

  1. Phase I Study and Biomarker Analysis of Lapatinib and Concurrent Radiation for Locally Advanced Breast Cancer

    PubMed Central

    Horton, Janet K.; Livasy, Chad A.; Shields, Janiel M.; Lawrence, Julia A.; Chiu, WingKeung M.; Ivanova, Anastasia; Ollila, David W.; Carey, Lisa A.; Halle, Jan S.; Sartor, Carolyn I.; Dees, E. Claire

    2012-01-01

    Purpose. This phase I study assessed the toxicity and safety of combining daily lapatinib with radiation therapy. Sequential tumor biopsies were obtained to evaluate changes in biomarkers, such as epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2) signaling pathways. Methods. Eligibility for this dose-escalation study included unresectable and locally recurrent or chemotherapy-refractory and locally advanced breast cancer, and adequate organ function. Patients underwent three serial biopsies: at baseline, after 1 week of lapatinib alone, and after 1 week of lapatinib and radiation. Endpoints included determination of toxicity, maximum tolerated dose, and analysis of the effect of lapatinib with or without radiation on EGFR and HER2 signaling pathways by immunohistochemistry. Results. Doses of lapatinib up to 1,500 mg/day were well tolerated. Toxicity of grade 3 or more was limited to radiation dermatitis and pain. Out of 19 patients treated, in field responses per Response Evaluation Criteria in Solid Tumors criteria were complete in four patients and partial in six patients. Serial biopsies were obtained in 16 patients with no complications. Total Her2 was relatively unchanged while phospho-Her2, phospho-Akt, and phospho-ERK showed variable responses to both lapatinib alone and dual therapy with lapatinib and radiation. Conclusions. The combination of lapatinib and radiation was well tolerated in this patient cohort. Overall local response rates were comparable to those reported in other studies in this patient population. Biopsies were safely performed at all time points. Inhibition of HER2 and downstream signaling pathways was identified, although no strong correlation with response was seen. PMID:23006498

  2. High-dose Helical Tomotherapy With Concurrent Full-dose Chemotherapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Chang, Jee Suk; Wang, Michael L.C.; Koom, Woong Sub; Yoon, Hong In; Chung, Yoonsun; Song, Si Young; Seong, Jinsil

    2012-08-01

    Purpose: To improve poor therapeutic outcome of current practice of chemoradiotherapy (CRT), high-dose helical tomotherapy (HT) with concurrent full-dose chemotherapy has been performed on patients with locally advanced pancreatic cancer (LAPC), and the results were analyzed. Methods and Materials: We retrospectively reviewed 39 patients with LAPC treated with radiotherapy using HT (median, 58.4 Gy; range, 50.8-59.9 Gy) and concomitant chemotherapy between 2006 and 2009. Radiotherapy was directed to the primary tumor with a 0.5-cm margin without prophylactic nodal coverage. Twenty-nine patients (79%) received full-dose (1000 mg/m{sup 2}) gemcitabine-based chemotherapy during HT. After completion of CRT, maintenance chemotherapy was administered to 37 patients (95%). Results: The median follow-up was 15.5 months (range, 3.4-43.9) for the entire cohort, and 22.5 months (range, 12.0-43.9) for the surviving patients. The 1- and 2-year local progression-free survival rates were 82.1% and 77.3%, respectively. Eight patients (21%) were converted to resectable status, including 1 with a pathological complete response. The median overall survival and progression-free survival were 21.2 and 14.0 months, respectively. Acute toxicities were acceptable with no gastrointestinal (GI) toxicity higher than Grade 3. Severe late GI toxicity ({>=}Grade 3) occurred in 10 patients (26%); 1 treatment-related death from GI bleeding was observed. Conclusion: High-dose helical tomotherapy with concurrent full-dose chemotherapy resulted in improved local control and long-term survival in patients with LAPC. Future studies are needed to widen the therapeutic window by minimizing late GI toxicity.

  3. Outcomes of pelvic exenteration for recurrent or primary locally advanced colorectal cancer

    PubMed Central

    Yang, Hwa Yeon; Park, Sung Chan; Hyun, Jong Hee; Seo, Ho Kyung

    2015-01-01

    Purpose The objective of this study was to assess the clinical outcomes of pelvic exenteration for patients with primary locally advanced colorectal cancer (LACRC) or locally recurrent colorectal cancer (LRCRC), and to identify clinically relevant prognostic factors. Methods Between January 2001 and December 2010, 40 consecutive patients with primary LACRC or LRCRC underwent pelvic exenteration at the National Cancer Center, Republic of Korea. We retrospectively reviewed their medical records. Results The median age was 59 years and the median follow-up time was 26 months (range, 1-117 months). The overall complication and in-hospital mortality rates were 70% (28/40) and 7.5% (3/40), respectively. The complication rates were similar between patients with primary LACRC (69.6%) and those with LRCRC (70.6%). The overall recurrence rate was 50% (17/34), and was lower in patients with primary LACRC than in patients with LRCRC (33.3% vs. 76.9%, P = 0.032). The 5-year overall survival was significantly different between primary LACRC and patients with LRCRC (58.7% vs. 11.8%, P = 0.022). Multivariate analysis revealed that radicality (R0 vs. R1/R2) was an independent prognostic factor for overall survival (P = 0.020). Conclusion The complication and operative mortality rates of pelvic exenteration remained high, but pelvic exenteration might provide an opportunity for long-term survival and good local control. Complete (R0) resection was the only independent prognostic factor for overall survival. PMID:26366382

  4. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

    PubMed Central

    2010-01-01

    Background The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC. Methods 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration NCT00444782 PMID:20478057

  5. [Hepatocellular carcinoma: occurrence, risk factors, biomarkers].

    PubMed

    Fehér, János; Lengyel, Gabriella

    2010-06-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death worldwide. Primary hepatocellular carcinoma can be found most frequently (80-90 %) in patients with liver cirrhosis. The most frequent causes of liver cirrhosis are chronic hepatitis B and C virus infections and chronic alcohol consumption. The occurrence of hepatocellular carcinoma is about 3-15 % in patients with alcoholic liver disease. Other predisposing causes can be: non-alcoholic steatohepatitis (NASH), obesity, diabetes mellitus, autoimmune hepatitis, intrahepatic biliary inflammations (primary biliary cirrhosis, primary sclerosing cholangitis), copper and iron metabolic diseases (Wilson-disease, haemochromatosis), congenital alpha-1-antitripsin deficiency. The causative role of hepatitis B és C viruses have been well established in the pathogenesis of liver cancer. Other pathogenic factors are smoking, and different chemical agents. Treatment options for these patients have previously been limited to best supportive care and palliative therapy. Beside surgical treatment (resection, liver transplantation) the invasive radiologic therapy also has been widely used. The effectiveness of targeted therapy with monoclonal antibodies or small-molecule kinase inhibitors has now been demonstrated for the treatment of different tumors. In year 2007, sorafenib, a multitargeted kinase inhibitor was introduced to clinical practice and found to prolong survival significantly for patients with advanced HCC. PMID:20494888

  6. Prevention of hepatocellular carcinoma.

    PubMed

    Kew, Michael C

    2010-01-01

    Because of its frequency and grave prognosis, preventing hepatocellular carcinoma is an urgent priority. Prevention should be possible because environmental carcinogens-chronic hepatitis B and C virus infections, dietary exposure to aflatoxins, and iron overload-cause the great majority of these tumors. Chronic hepatitis B virus infection accounts for 55% of global hepatocellular carcinomas and 80% of those in the high-incidence Asia Pacific and sub-Saharan African regions. In these regions the infection that becomes chronic is predominantly acquired very early in life. A safe and effective vaccine against this virus is available and its universal inclusion in the immunization of infants has already resulted in a marked reduction of chronic infection and a 70% decrease in the occurrence of hepatocellular carcinoma in those immunized. Chronic hepatitis C virus infection is the major cause of hepatocellular carcinoma in industrialized countries. The infection is mainly acquired in adulthood and, until a vaccine becomes available, prevention will consist mainly of identifying, counselling, and treating chronically infected individuals, preventing spread of the virus by the use of safe injection practices (particularly in intravenous drug abusers), and screening all donated blood for the presence of the virus. 4.5 billion of the world.s population are exposed to dietary aflatoxins. Prevention involves treating susceptible crops to prevent fungal contamination, and handling the foodstuffs in such a way as to prevent contamination during storage. Iron overload in hereditary hemochromatosis can be prevented by repeated venesection and in African dietary iron overload by fermenting the home-brewed beer in iron-free containers. PMID:20526004

  7. Neoadjuvant Therapy of DOF Regimen Plus Bevacizumab Can Increase Surgical Resection Ratein Locally Advanced Gastric Cancer

    PubMed Central

    Ma, Junxun; Yao, Sheng; Li, Xiao-Song; Kang, Huan-Rong; Yao, Fang-Fang; Du, Nan

    2015-01-01

    Abstract Locally advanced gastric cancer (LAGC) is best treated with surgical resection. Bevacizumab in combination with chemotherapy has shown promising results in treating advanced gastric cancer. This study aimed to investigate the efficacy of neoadjuvant chemotherapy using the docetaxel/oxaliplatin/5-FU (DOF) regimen and bevacizumab in LAGC patients. Eighty LAGC patients were randomized to receive DOF alone (n = 40) or DOF plus bevacizumab (n = 40) as neoadjuvant therapy before surgery. The lesions were evaluated at baseline and during treatment. Circulating tumor cells (CTCs) were counted using the FISH test. Patients were followed up for 3 years to analyze the disease-free survival (DFS) and overall survival (OS). The total response rate was significantly higher in the DOF plus bevacizumab group than the DOF group (65% vs 42.5%, P = 0.0436). The addition of bevacizumab significantly increased the surgical resection rate and the R0 resection rate (P < 0.05). The DOF plus bevacizumab group showed significantly greater reduction in CTC counts after neoadjuvant therapy in comparison with the DOF group (P = 0.0335). Although the DOF plus bevacizumab group had significantly improved DFS than the DOF group (15.2 months vs 12.3 months, P = 0.013), the 2 groups did not differ significantly in OS (17.6 ± 1.8 months vs 16.4 ± 1.9 months, P = 0.776. Cox proportional model analysis showed that number of metastatic lymph nodes, CTC reduction, R0 resection, and neoadjuvant therapy are independent prognostic factors for patients with LAGC. Neoadjuvant of DOF regimen plus bevacizumab can improve the R0 resection rate and DFS in LAGC. These beneficial effects might be associated with the reduction in CTC counts. PMID:26496252

  8. Dose escalation for unresectable locally advanced non-small cell lung cancer: end of the line?

    PubMed

    Hong, Julian C; Salama, Joseph K

    2016-02-01

    Radiation Therapy Oncology Group (RTOG) 0617 was a randomized trial that investigated both the impact of radiation dose-escalation and the addition of cetuximab on the treatment of non-small cell lung cancer (NSCLC). The results of RTOG 0617 were surprising, with the dose escalation randomization being closed prematurely due to futility stopping rules, and cetuximab ultimately showing no overall survival benefit. Locally advanced unresectable NSCLC has conventionally been treated with concurrent chemoradiation. Though advances in treatment technology have improved the ability to deliver adequate treatment dose, the foundation for radiotherapy (RT) has remained the same since the 1980s. Since then, progressive studies have sought to establish the safety and efficacy of escalating radiation dose to loco-regional disease. Though RTOG 0617 did not produce the anticipated result, much interest remains in dose escalation and establishing an explanation for the findings of this study. Cetuximab was also not found to provide a survival benefit when applied to an unselected population. However, planned retrospective analysis suggests that those patients with high epidermal growth factor receptor (EGFR) expression may benefit, suggesting that cetuximab should be applied in a targeted fashion. We discuss the results of RTOG 0617 and additional findings from post-hoc analysis that suggest that dose escalation may be limited by normal tissue toxicity. We also present ongoing studies that aim to address potential causes for mortality in the dose escalation arm through adaptive or proton therapy, and are also leveraging additional concurrent systemic agents such as tyrosine kinase inhibitors (TKIs) for EGFR-activating mutations or EML4-ALK rearrangements, and poly (ADP-ribose) polymerase (PARP) inhibitors. PMID:26958507

  9. Chemoradiotherapy with capecitabine for locally advanced anal carcinoma: an alternative treatment option

    PubMed Central

    Meulendijks, D; Dewit, L; Tomasoa, N B; van Tinteren, H; Beijnen, J H; Schellens, J H M; Cats, A

    2014-01-01

    Background: Capecitabine is an established treatment alternative to intravenous 5-fluorouracil (5-FU) for patients with rectal cancer receiving chemoradiotherapy. Its place in the treatment of locally advanced anal carcinoma (AC), however, remains undetermined. We investigated whether capecitabine is as effective as 5-FU in the treatment of patients with locally advanced AC. Methods: One hundred and five patients with squamous cell AC stage T2-4 (T2>4 cm), N0-1, M0 or T1-4, N2-3, M0, were included in this retrospective study. Forty-seven patients were treated with continuous 5-FU (750 mg m−2) on days 1–5 and 29–33, mitomycin C (MMC, 10 mg m−2) on day 1, and radiotherapy; 58 patients were treated with capecitabine (825 mg m−2 b.i.d. on weekdays), MMC (10 mg m−2) on day 1, and radiotherapy. The primary end points of the study were: clinical complete response rate, locoregional control (LRC) and overall survival (OS). Secondary end points were: colostomy-free survival (CFS), toxicity and associations of genetic polymorphisms (GSTT1, GSTM1, GSTP1 and TYMS) with outcome and toxicity. Results: Clinical complete response was achieved in 41/46 patients (89.1%) with 5-FU and in 52/58 patients (89.7%) with capecitabine. Three-year LRC was 76% and 79% (P=0.690, log-rank test), 3-year OS was 78% and 86% (P=0.364, log-rank test) and CFS was 65% and 79% (P=0.115, log-rank test) for 5-FU and capecitabine, respectively. GSTT1 and TYMS genotypes were associated with severe (grade 3–4) toxicity. Conclusions: Capecitabine combined with MMC and radiotherapy was equally effective as 5-FU-based chemoradiotherapy. This study shows that capecitabine can be used as an acceptable alternative to 5-FU for the treatment of AC. PMID:25167226

  10. Radiation Dose-Response Model for Locally Advanced Rectal Cancer After Preoperative Chemoradiation Therapy

    SciTech Connect

    Appelt, Ane L.; Ploen, John; Vogelius, Ivan R.; Bentzen, Soren M.; Jakobsen, Anders

    2013-01-01

    Purpose: Preoperative chemoradiation therapy (CRT) is part of the standard treatment of locally advanced rectal cancers. Tumor regression at the time of operation is desirable, but not much is known about the relationship between radiation dose and tumor regression. In the present study we estimated radiation dose-response curves for various grades of tumor regression after preoperative CRT. Methods and Materials: A total of 222 patients, treated with consistent chemotherapy and radiation therapy techniques, were considered for the analysis. Radiation therapy consisted of a combination of external-beam radiation therapy and brachytherapy. Response at the time of operation was evaluated from the histopathologic specimen and graded on a 5-point scale (TRG1-5). The probability of achieving complete, major, and partial response was analyzed by ordinal logistic regression, and the effect of including clinical parameters in the model was examined. The radiation dose-response relationship for a specific grade of histopathologic tumor regression was parameterized in terms of the dose required for 50% response, D{sub 50,i}, and the normalized dose-response gradient, {gamma}{sub 50,i}. Results: A highly significant dose-response relationship was found (P=.002). For complete response (TRG1), the dose-response parameters were D{sub 50,TRG1} = 92.0 Gy (95% confidence interval [CI] 79.3-144.9 Gy), {gamma}{sub 50,TRG1} = 0.982 (CI 0.533-1.429), and for major response (TRG1-2) D{sub 50,TRG1} and {sub 2} = 72.1 Gy (CI 65.3-94.0 Gy), {gamma}{sub 50,TRG1} and {sub 2} = 0.770 (CI 0.338-1.201). Tumor size and N category both had a significant effect on the dose-response relationships. Conclusions: This study demonstrated a significant dose-response relationship for tumor regression after preoperative CRT for locally advanced rectal cancer for tumor dose levels in the range of 50.4-70 Gy, which is higher than the dose range usually considered.

  11. Phase II Trial of Neoadjuvant Bevacizumab, Capecitabine, and Radiotherapy for Locally Advanced Rectal Cancer

    SciTech Connect

    Crane, Christopher H.; Eng, Cathy; Feig, Barry W.; Das, Prajnan; Skibber, John M.; Chang, George J.; Wolff, Robert A.; Krishnan, Sunil; Hamilton, Stanley; Janjan, Nora A.; Maru, Dipen M.; Ellis, Lee M.; Rodriguez-Bigas, Miguel A.

    2010-03-01

    Purpose: We designed this Phase II trial to assess the efficacy and safety of the addition of bevacizumab to concurrent neoadjuvant capecitabine-based chemoradiation in locally advanced rectal cancer. Methods: Between April 2004 and December 2007, 25 patients with clinically staged T3N1 (n = 20) or T3N0 (n = 5) rectal cancer received neoadjuvant therapy with radiotherapy (50.4 Gy in 28 fractions over 5.5 weeks), bevacizumab every 2 weeks (3 doses of 5 mg/kg), and capecitabine (900 mg/m{sup 2} orally twice daily only on days of radiation), followed by surgical resection a median of 7.3 weeks later. Results: Procedures included abdominoperineal resection (APR; 6 patients), proctectomy with coloanal anastamosis (8 patients), low anterior resection (10 patients), and local excision (1 patient). Eight (32%) of 25 patients had a pathologic complete response, and 6 (24%) of 25 had <10% viable tumor cells in the specimen. No patient had Grade 3 hand-foot syndrome, gastrointestinal toxicity, or significant hematologic toxicity. Three wound complications required surgical intervention (one coloanal anastamostic dehiscence requiring completion APR and two perineal wound dehiscences after initial APR). Five minor complications occurred that resolved without operative intervention. With a median follow-up of 22.7 months (range, 4.5-32.4 months), all patients were alive; one patient has had a recurrence in the pelvis (2-year actuarial rate, 6.2%) and 3 had distant recurrences. Conclusions: The addition of bevacizumab to neoadjuvant chemoradiation resulted in encouraging pathologic complete response without an increase in acute toxicity. The impact of bevacizumab on perineal wound and anastamotic healing due to concurrent bevacizumab requires further study.

  12. Preoperative chemoradiation for locally advanced rectal cancer: comparison of three radiation dose and fractionation schedules

    PubMed Central

    Park, Shin-Hyung; Kim, Jae-Chul

    2016-01-01

    Purpose: The standard radiation dose for patients with locally rectal cancer treated with preoperative chemoradiotherapy is 45–50 Gy in 25–28 fractions. We aimed to assess whether a difference exists within this dose fractionation range. Materials and Methods: A retrospective analysis was performed to compare three dose fractionation schedules. Patients received 50 Gy in 25 fractions (group A), 50.4 Gy in 28 fractions (group B), or 45 Gy in 25 fractions (group C) to the whole pelvis, as well as concurrent 5-fluorouracil. Radical resection was scheduled for 8 weeks after concurrent chemoradiotherapy. Results: Between September 2010 and August 2013, 175 patients were treated with preoperative chemoradiotherapy at our institution. Among those patients, 154 were eligible for analysis (55, 50, and 49 patients in groups A, B, and C, respectively). After the median follow-up period of 29 months (range, 5 to 48 months), no differences were found between the 3 groups regarding pathologic complete remission rate, tumor regression grade, treatment-related toxicity, 2-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, or overall survival. The circumferential resection margin width was a prognostic factor for 2-year locoregional recurrence-free survival, whereas ypN category was associated with distant metastasis-free survival, disease-free survival, and overall survival. High tumor regression grading score was correlated with 2-year distant metastasis-free survival and disease-free survival in univariate analysis. Conclusion: Three different radiation dose fractionation schedules, within the dose range recommended by the National Comprehensive Cancer Network, had no impact on pathologic tumor regression and early clinical outcome for locally advanced rectal cancer. PMID:27306773

  13. Clinical Outcome of Palliative Radiotherapy for Locally Advanced Symptomatic Gastric Cancer in the Modern Era

    PubMed Central

    Tey, Jeremy; Choo, Bok Ai; Leong, Cheng Nang; Loy, En Yun; Wong, Lea Choung; Lim, Keith; Lu, Jiade Jay; Koh, Wee Yao

    2014-01-01

    Abstract The purpose of this study was to report the outcomes of patients with symptomatic locally advanced/recurrent gastric cancer treated with radiotherapy (RT) using modern 3-dimensional conformal techniques. We retrospectively reviewed patients who had palliative RT for index symptoms of gastric bleeding, pain, and obstruction. Study endpoints included symptom response, median survival, and treatment toxicity. Of 115 patients with median age of 77 years, 78 (67.8%) patients had metastatic disease at the time of treatment. Index symptoms were gastric bleeding, pain, and obstruction in 89.6%, 9.2%, and 14.3% of patients, respectively. Dose fractionation regimen ranged from 8-Gy single fraction to 40 Gy in 16 fractions. One hundred eleven patients (93.3%) were computed tomography (CT) planned. Median follow-up was 85 days. Response rates for bleeding, pain, and obstruction were 80.6% (83/103), 45.5% (5/11), and 52.9% (9/17), respectively, and median duration of response was 99 days, 233 days, and 97 days, respectively. Median survival was 85 days. Actuarial 12-month survival was 15.3%. There was no difference in response rates between low (≤39 Gy) and high (>39 Gy) biologically effective dose (BED) regimens (α/β ratio = 10). Median survival was significantly longer in patients who responded to RT compared with patients who did not (113.5 vs 47 days, P < 0.001). Three patients (2.6%) had grade 3 Common Toxicity Criteria equivalent toxicity (nausea/vomiting/anorexia). External beam RT delivered using 3-dimensional conformal techniques is highly effective and well tolerated in the local palliation of gastric cancer, with palliation lasting the majority of patient’s lives. Short (≤39 Gy BED) RT schedules are adequate for effective symptom palliation. A phase II study of palliative gastric RT is ongoing. PMID:25396330

  14. Radiochemotherapy With Cetuximab, Cisplatin, and Amifostine for Locally Advanced Head and Neck Cancer: A Feasibility Study

    SciTech Connect

    Koukourakis, Michael I.; Karapantzos, Ilias; Daniilidis, Vassilios; Kouskoukis, Constantinos

    2010-05-01

    Purpose: Radiotherapy (RT) combined with cisplatin or cetuximab is the standard of care for patients with locally advanced head/neck cancer (LA-HNC). The feasibility of radiochemotherapy with cisplatin and cetuximab, supported with amifostine, was herein investigated. Methods and Materials: Forty-three patients with LA-HNC were recruited. Conformal hypofractionated/accelerated RT with amifostine cytoprotection (2.7 Gy/fraction, 21 fractions in 4 weeks) was combined with cisplatin (30 mg/m{sup 2}/week) and cetuximab (standard weekly regimen) therapy. The dose of amifostine was individualized according to tolerance. Results: A high daily amifostine dose (750-1,000 mg) was tolerated by 41.8% of patients, and a standard dose (500 mg) was tolerated by 34.9% of patients. A high amifostine dose was linked to reduced RT delays (p = 0.0003). Grade 3 to 4 (3-4) mucositis occurred in 7/43 (16.2%) patients, and fungal infections occurred in 18/43 (41.8%) patients. Radiation dermatitis was not aggravated. Interruption of cetuximab due to acneiform rash was necessary in 23.3% of patients, while amifostine-related fever and rash were not observed. Severe late radiation sequelae consisted of laryngeal edema (9% laryngeal cases) and cervical strictures (33% of hypopharyngeal cases). Good salivary function was preserved in 6/11 (54.5%) nasopharyngeal cancer patients. The complete response rate was 68.5%, reaching 77.2% in patients with minor radiotherapy delays. The 24-month local control and survival rates were 72.3% and 91%, respectively (median follow-up was 13 months.). Conclusions: In this feasibility study, weekly administration of cisplatin and cetuximab was safely combined with accelerated RT, supported with amifostine, at the cost of a high incidence of acneiform rash but a reduced incidence of amifostine-related fever/rash. A high daily dose of amifostine allows completion of therapy with minor delays.

  15. Concurrent Chemoradiotherapy Versus Chemotherapy Alone for Unresectable Locally Advanced Pancreatic Cancer: A Retrospective Cohort Study

    PubMed Central

    Choi, Younak; Oh, Do-Youn; Kim, Kyubo; Chie, Eui Kyu; Kim, Tae-Yong; Lee, Kyung-Hun; Han, Sae-Won; Im, Seock-Ah; Kim, Tae-You; Ha, Sung Whan; Bang, Yung-Jue

    2016-01-01

    Purpose The optimal treatment strategy for locally advanced pancreatic cancer (LAPC), particularly the role of concurrent chemoradiotherapy (CCRT), remains debatable. We compared the clinical outcomes of CCRT and palliative chemotherapy alone (CA) in patients with unresectable LAPC. Materials and Methods Patients with LAPC who were consecutively treated between 2003 and 2010 were included. Resectability was evaluated according to National Comprehensive Cancer Network ver. 1.2012. The clinical outcomes for each treatment group (CCRT vs. CA) were evaluated retrospectively. Results Sixty-three patients (58.9%) and 44 patients (41.1%) were treated with CCRT and CA, respectively. The CCRT cohort included patients who were treated with CCRT with or without chemotherapy backbone (CCRT alone, induction chemotherapy-CCRT, CCRT-maintenance chemotherapy, and induction-CCRT-maintenance chemotherapy). Median progression-free survival (PFS) and overall survival (OS) of all patients were 7.2 months and 13.1 months. PFS of the CCRT and CA groups was 9.0 months and 4.4 months, respectively (p=0.020). OS of the CCRT and CA groups was 15.4 months and 9.3 months, respectively (p=0.011). In multivariate analysis, the adjusted hazard ratio of CCRT was 0.536 (p=0.003) for OS and 0.667 (p=0.078) for PFS. Although the pattern of failure was similar in the CCRT and CA groups, the times to both local and distant failure were significantly longer in the CCRT group. Conclusion In patients with unresectable LAPC, those who underwent CCRT during their entire treatment courses had longer OS than patients treated with chemotherapy alone. PMID:26511805

  16. Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience

    PubMed Central

    Yeh, Matthew M; Yeung, Raymond S; Apisarnthanarax, Smith; Bhattacharya, Renuka; Cuevas, Carlos; Harris, William P; Hon, Tony Lim Kiat; Padia, Siddharth A; Park, James O; Riggle, Kevin M; Daoud, Sayed S

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would: (1) greatly facilitate the identification of patients at risk; (2) prompt efforts to decrease risk factors; and (3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC, this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, non-invasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics. PMID:26085907

  17. Update in management of hepatocellular carcinoma in Eastern population.

    PubMed

    Chu, Kevin Ka Wan; Cheung, Tan To

    2015-06-18

    Hepatocellular carcinoma (HCC) is one of the commonest malignant tumours in the East. Although the management of HCC in the West is mainly based on the Barcelona Clinic for Liver Cancer staging, it is considered too conservative by Asian countries where the number of HCC patients is huge. Scientific and clinical advances were made in aspects of diagnosis, staging, and treatment of HCC. HCC is well known to be associated with cirrhosis and the treatment of HCC must take into account the presence and stage of chronic liver disease. The major treatment modalities of HCC include: (1) surgical resection; (2) liver transplantation; (3) local ablation therapy; (4) transarterial locoregional treatment; and (5) systemic treatment. Among these, resection, liver transplantation and ablation therapy for small HCC are considered as curative treatment. Portal vein embolisation and the associating liver partition with portal vein ligation for staged hepatectomy may reduce dropout in patients with marginally resectable disease but the midterm and long-term results are still to be confirmed. Patient selection for the best treatment modality is the key to success of treatment of HCC. The purpose of current review is to provide a description of the current advances in diagnosis, staging, pre-operative liver function assessment and treatment options for patients with HCC in the east. PMID:26085915

  18. Update in management of hepatocellular carcinoma in Eastern population

    PubMed Central

    Chu, Kevin Ka Wan; Cheung, Tan To

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the commonest malignant tumours in the East. Although the management of HCC in the West is mainly based on the Barcelona Clinic for Liver Cancer staging, it is considered too conservative by Asian countries where the number of HCC patients is huge. Scientific and clinical advances were made in aspects of diagnosis, staging, and treatment of HCC. HCC is well known to be associated with cirrhosis and the treatment of HCC must take into account the presence and stage of chronic liver disease. The major treatment modalities of HCC include: (1) surgical resection; (2) liver transplantation; (3) local ablation therapy; (4) transarterial locoregional treatment; and (5) systemic treatment. Among these, resection, liver transplantation and ablation therapy for small HCC are considered as curative treatment. Portal vein embolisation and the associating liver partition with portal vein ligation for staged hepatectomy may reduce dropout in patients with marginally resectable disease but the midterm and long-term results are still to be confirmed. Patient selection for the best treatment modality is the key to success of treatment of HCC. The purpose of current review is to provide a description of the current advances in diagnosis, staging, pre-operative liver function assessment and treatment options for patients with HCC in the east. PMID:26085915

  19. Primary chemotherapy with adriamycin, cisplatin, vincristine and cyclophosphamide in locally advanced thymomas: a single institution experience.

    PubMed

    Berruti, A; Borasio, P; Gerbino, A; Gorzegno, G; Moschini, T; Tampellini, M; Ardissone, F; Brizzi, M P; Dolcetti, A; Dogliotti, L

    1999-11-01

    From 1990 to 1997, 16 consecutive patients with stage III and IVa invasive thymoma were treated in a single institution with primary chemotherapy consisting in adriamycin (40 mg m(-2)), cisplatin (50 mg m(-2)) administered intravenously on day 1, vincristine (0.6 mg m(-2)) on day 2 and cyclophosphamide (700 mg m(-2)) on day 4 (ADOC). The courses were repeated every 3 weeks. The aim was to evaluate the impact of this cytotoxic regimen with respect to response rate, per cent of patients radically resected, time to progression and overall survival. Two complete responses (one clinical and one pathological) and 11 partial responses were observed (overall response rate 81.2%); two patients had stable disease and one progressed. Toxicity was mild as only two patients developed grade III/IV neutropenia and one patient grade III nausea/vomiting. Nine patients were radically resected (five out of ten with stage III, and four out of six with stage IVa). Median time to progression and overall survival was 33.2 and 47.5 months respectively. Three patients were alive and disease free after more than 5 years. The ADOC scheme is highly active and manageable in the treatment of locally advanced thymoma. As a preoperative approach it should be offered to patients not amenable to surgery or to those surgically resectable but with a great deal of morbidity. PMID:10555755

  20. The best timing for administering systemic chemotherapy in patients with locally advanced rectal cancer

    PubMed Central

    Shimodaira, Yusuke; Harada, Kazuto; Lin, Quan

    2016-01-01

    Over the past several decades, outcomes for patients with rectal cancer have improved considerably. However, several questions have emerged as survival times have lengthened and quality of life has improved for these patients. Currently patients with locally advanced rectal cancer (LARC) are often recommended multimodality therapy with fluoropyrimidine-based chemotherapy (CT) and radiation followed by total mesorectal excision (TME), with consideration given to FOLFOX before chemoradiotherapy (CRT). Recently, Garcia-Aguilar and colleagues reported in Lancet Oncology that the addition of mFOLFOX6 administered between CRT and surgery affected the number of patients achieving pathologic complete response (pathCR), which is of great interest from the standpoint of pursuit of optimal timing of systemic CT delivery. This was a multicenter phase II study consisting of 4 sequential treatment groups of patients with LARC, and they reported that patients given higher number CT cycles between CRT and surgery achieved higher rates of pathCR than those given standard treatment. There was no association between response improvement and tumor progression, increased technical difficulty, or surgical complications. Ongoing phase III clinical trial further assessing this strategy might result in a paradigm shift. PMID:26889491

  1. Electrochemical characterization and occluded environment analysis of localized corrosion in advanced aluminum alloys

    SciTech Connect

    Wall, F.D.; Stoner, G.E.

    1994-12-31

    In order for advanced aluminum alloys to be used in structural applications it is necessary to understand and mitigate failures that can occur due to localized corrosion events. Mechanical and electrochemical stresses interacting with a microstructural heterogeneity can result in the rapid growth of a flaw in the material; this phenomenon is a form of environmentally assisted cracking (EAC). One possible mechanism of EAC in Al-Li-X alloys is the preferential dissolution of an electrochemically active microstructural feature along a grain or sub-grain boundary. To examine this mechanism it is necessary to obtain information on the occluded environment that develops in a growing crack and the electrochemical behavior of boundary phases in the occluded environment. The electrochemistry of three relevant boundary phases (matrix phase (SHT 2095), T{sub 1} precipitate (Al{sub 2}CuLi) and Cu-depleted zone (99.99% Al)) in several model environments has been documented using a variety of electrochemical techniques including scratching and straining electrode experiments. The electrochemical behavior of these phases has been linked to the SCC behavior of several Al-Li-X alloys using constant load testing under applied potentials in NaCl/Li{sub 2}CO{sub 3} and NaCl/Na{sub 2}CrO{sub 4} environments. The occluded environment model is being evaluated and refined by analysis of occluded chemistries using pH measurements and capillary electrophoresis.

  2. Prognostic Impact of Pretreatment Plasma Fibrinogen in Patients with Locally Advanced Oral and Oropharyngeal Cancer

    PubMed Central

    Holzinger, Daniel; Danilovic, Ivan; Seemann, Rudolf; Kornek, Gabriela; Engelmann, Johannes; Pillerstorff, Robert; Holawe, Simone; Psyrri, Amanda; Erovic, Boban M.; Farwell, Gregory; Perisanidis, Christos

    2016-01-01

    Background We aimed to determine the prognostic significance of pretreatment plasma fibrinigen in patients with oral and oropharyngeal squamous cell carcinoma (OOSCC). Methods A cohort of 183 patients with locally advanced OOSCC receiving preoperative chemoradiotherapy was retrospectively examined. Using ROC curve analysis, a pretreatment plasma fibrinogen cutoff value of 447mg/dL was determined. The primary endpoints were overall survival and recurrence-free survival. A secondary endpoint was to determine whether pretreatment plasma fibrinogen could predict treatment response to neoadjuvant chemoradiotherapy. Cox regression models and Kaplan–Meier curves were used for survival analyses. Results Seventy-one patients had an elevated pretreatment plasma fibrinogen (fibrinogen >447mg/dL). Patients with high fibrinogen showed significantly higher pathologic stages after neoadjuvant treatment than those with low fibrinogen (p = 0.037). In univariate analysis, elevated fibrinogen was associated with poor overall survival (p = 0.005) and recurrence-free survival (p = 0.008) Multivariate analysis revealed that elevated fibrinogen remained an independent risk factor for death (hazard ratio 1.78, 95% CI 1.09–2.90, p = 0.021) and relapse (hazard ratio 1.78, 95% CI 1.11–2.86, p = 0.016). Conclusion Elevated pretreatment plasma fibrinogen is associated with lack of response to neoadjuvant chemoradiotherapy and reduced OS and RFS in patients with OOSCC. Thus, plasma fibrinogen may emerge as a novel prognostic indicator and a potential therapeutic target in OOSCC. PMID:27362659

  3. Photodynamic therapy of locally advanced pancreatic cancer (VERTPAC study): final clinical results

    NASA Astrophysics Data System (ADS)

    Huggett, M. T.; Jermyn, M.; Gillams, A.; Mosse, S.; Kent, E.; Bown, S. G.; Hasan, T.; Pogue, B. W.; Pereira, S. P.

    2013-03-01

    We undertook a phase I dose-escalation study of verteporfin photodynamic therapy (PDT) in 15 patients with locally advanced pancreatic cancer. Needle placement and laser delivery were technically successful in all patients. Thirteen patients were treated with a single laser fibre. Three treatments were carried out each at 5, 10 and 20 J/cm2; and 5 treatments (4 patients) at 40 J/cm2. A further 2 patients were treated with 2 or 3 laser fibres at 40 J/cm2. Tumour necrosis was measured on CT (computed tomography) by two radiologists 5 days after treatment. There was a clear dosedependent increase in necrosis with a median area of 20 x 16 mm (range 18 x 16 to 35 x 30 mm) at 40 J/cm2. In the 2 patients treated with multiple fibres, necrosis was 40 x 36 mm and 30 x 28 mm, respectively. There were no early complications in patients treated with a single fibre. Both patients treated with multiple fibres had evidence on CT of inflammatory change occurring anterior to the pancreas but without clinical deterioration. These results suggest that single fibre verteporfin PDT is safe in a clinical setting up to 40J/cm2 and produces a dose-dependent area of pancreatic necrosis.

  4. Immunotherapy in locally-advanced non-small cell lung cancer: releasing the brakes on consolidation?

    PubMed Central

    2016-01-01

    Locally-advanced non-small cell lung cancer (LA-NSCLC) is optimally treated with definitive chemoradiation or surgery in combination with chemotherapy or chemoradiation. Prognosis, however, remains poor, and attempts to improve outcomes using consolidation or maintenance chemotherapy have not improved overall survival. Given the limited success of traditional cytotoxic chemotherapies as maintenance therapy for LA-NSCLC, recent studies have investigated the role of novel agents such as maintenance or consolidation, including antiangiogenic agents and molecular targeted therapy. With multiple newly reported trials demonstrating improved outcomes with immunotherapy over cytotoxic chemotherapy for stage IV NSCLC, integrating immunotherapy with definitive chemoradiation regimens or as consolidative therapy for LA-NSCLC is an attractive option. The recently published START trial is the first to test immunotherapy in LA-NSCLC in a randomized, phase III setting. In that trial, the administration of maintenance tecemotide (L-BLP25), which induces a T-cell response to the mucin 1 (MUC1) glycoprotein, was found to be well tolerated and improve overall survival compared with placebo among patients receiving concurrent, but not sequential, chemoradiation. Despite the promising findings of this trial, numerous questions regarding immunotherapy for LA-NSCLC remain, and several additional immunotherapy trials are underway or planned in this patient population. PMID:26958509

  5. Transcript Profiling Distinguishes Complete Treatment Responders With Locally Advanced Cervical Cancer1234

    PubMed Central

    Fernandez-Retana, Jorge; Lasa-Gonsebatt, Federico; Lopez-Urrutia, Eduardo; Coronel-Martínez, Jaime; Cantu De Leon, David; Jacobo-Herrera, Nadia; Peralta-Zaragoza, Oscar; Perez-Montiel, Delia; Reynoso-Noveron, Nancy; Vazquez-Romo, Rafael; Perez-Plasencia, Carlos

    2015-01-01

    Cervical cancer (CC) mortality is a major public health concern since it is the second cause of cancer-related deaths among women. Patients diagnosed with locally advanced CC (LACC) have an important rate of recurrence and treatment failure. Conventional treatment for LACC is based on chemotherapy and radiotherapy; however, up to 40% of patients will not respond to conventional treatment; hence, we searched for a prognostic gene signature able to discriminate patients who do not respond to the conventional treatment employed to treat LACC. Tumor biopsies were profiled with genome-wide high-density expression microarrays. Class prediction was performed in tumor tissues and the resultant gene signature was validated by quantitative reverse transcription–polymerase chain reaction. A 27-predictive gene profile was identified through its association with pathologic response. The 27-gene profile was validated in an independent set of patients and was able to distinguish between patients diagnosed as no response versus complete response. Gene expression analysis revealed two distinct groups of tumors diagnosed as LACC. Our findings could provide a strategy to select patients who would benefit from neoadjuvant radiochemotherapy-based treatment. PMID:25926073

  6. Transcript profiling distinguishes complete treatment responders with locally advanced cervical cancer.

    PubMed

    Fernandez-Retana, Jorge; Lasa-Gonsebatt, Federico; Lopez-Urrutia, Eduardo; Coronel-Martínez, Jaime; Cantu De Leon, David; Jacobo-Herrera, Nadia; Peralta-Zaragoza, Oscar; Perez-Montiel, Delia; Reynoso-Noveron, Nancy; Vazquez-Romo, Rafael; Perez-Plasencia, Carlos

    2015-04-01

    Cervical cancer (CC) mortality is a major public health concern since it is the second cause of cancer-related deaths among women. Patients diagnosed with locally advanced CC (LACC) have an important rate of recurrence and treatment failure. Conventional treatment for LACC is based on chemotherapy and radiotherapy; however, up to 40% of patients will not respond to conventional treatment; hence, we searched for a prognostic gene signature able to discriminate patients who do not respond to the conventional treatment employed to treat LACC. Tumor biopsies were profiled with genome-wide high-density expression microarrays. Class prediction was performed in tumor tissues and the resultant gene signature was validated by quantitative reverse transcription-polymerase chain reaction. A 27-predictive gene profile was identified through its association with pathologic response. The 27-gene profile was validated in an independent set of patients and was able to distinguish between patients diagnosed as no response versus complete response. Gene expression analysis revealed two distinct groups of tumors diagnosed as LACC. Our findings could provide a strategy to select patients who would benefit from neoadjuvant radiochemotherapy-based treatment. PMID:25926073

  7. Neoadjuvant Chemotherapy for Locally Advanced Squamous Carcinoma of Oral Cavity: a Pilot Study.

    PubMed

    Sadighi, Sanambar; Keyhani, Amanolah; Harirchi, Iraj; Garajei, Ata; Aghili, Mahdi; Kazemian, Ali; Motiee Langroudi, Maziar; Zendehdel, Kazem; Nikparto, Nariman

    2015-01-01

    To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF) induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years). Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%). No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014). Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes. PMID:26069178

  8. Maintenance therapy with capecitabine in patients with locally advanced unresectable pancreatic adenocarcinoma.

    PubMed

    Saif, Muhammad Wasif; Ledbetter, Leslie; Kaley, Kristin; Garcon, Marie Carmel; Rodriguez, Teresa; Syrigos, Kostas N

    2014-09-01

    Therapeutic options for locally advanced pancreatic cancer (LAPC) include concurrent chemoradiation, induction chemotherapy followed by chemoradiation or systemic therapy alone. The original Gastro-Intestinal Study Group and Eastern Cooperative Oncology Group studies defined fluorouracil (5-FU) with concurrent radiation therapy followed by maintenance 5-FU until progression, as the standard therapy for this subset of patients. Although this combined therapy has been demonstrated to increase local control and median survival from 8 to 12 months, almost all patients succumb to the disease secondary to either local or distant recurrence. Our earlier studies provided a strong rationale for the use of capecitabine in combination with concurrent radiation followed by maintenance capecitabine therapy. To report our clinical experience, we retrospectively evaluated our patients who were treated with maintenance capecitabine. We reviewed the medical records of patients with LAPC who received treatment with capecitabine and radiation, followed by a 4-week rest, then capecitabine alone 1,000 mg twice daily (ECOG performance status 2 or age >70 years) or 1,500 mg twice daily for 14 days every 3 weeks until progressive disease. We treated 43 patients between September 2004 and September 2012. The population consisted of 16 females and 25 males, with a median age of 64 years (range, 38-80 years). Patients received maintenance capecitabine for median duration of 9 months (range, 3-18 months). The median overall survival (OS) for these patients was 17 months, with two patients still living and receiving therapy. The 6-month survival rate was 91% (39/43), 1-year survival rate was 72% (31/43) and 2-year OS rate was 26% (11/43). Grade 3 or 4 toxicity was observed rarely: Hand-foot syndrome (HFS) in two patients, diarrhea in one patient and peripheral neuropathy in one patient, and there was no mortality directly related to treatment. Capecitabine maintenance therapy following

  9. Recurrence pattern in patients with locally advanced renal cell carcinoma: The implications of clinicopathological variables

    PubMed Central

    Sameh, Wael M.; Hashad, Mohammed M.; Eid, Ahmed A.; Abou Yousif, Tamer A.; Atta, Mohammed A.

    2012-01-01

    Objectives Recurrence rates for patients with locally advanced renal cell carcinoma (LARCC) remain high. To date the predictors of recurrence in those patients remain controversial. The aim of the present study was to assess the relapse pattern in those patients and identify predictors for recurrence. Patients and methods We evaluated retrospectively 112 consecutive patients who underwent surgery for LARCC (T3–T4N0M0) between January 2000 and December 2010. Clinical and pathological data were collected from hospital medical records and compiled into a computerized database. Studied variables were age, mode of presentation, Tumour-Node-Metastasis (TNM) stage, Fuhrman nuclear grade, histological subtype, tumour size, venous thrombus level, collecting-system invasion and sarcomatoid differentiation. Recurrence-free survival (RFS) was estimated using the Kaplan–Meier method. Univariate and multivariate analyses were conducted. Results Patients were followed for a mean and median follow-up of 33 and 24 months, respectively, after surgery. During the follow-up, recurrences (distant and/or local) were recorded in 58 patients, representing 52% of the cohort. The mean and median times to recurrence were 25 and 13 months, respectively. Sites of recurrence were multiple in 36 patients (62%), lung only in 14 (24%), and local in eight (14%). RFS rates at 1, 2, and 5 years were 50%, 43% and 34%, respectively, while the median RFS was 23.7 months. Using univariate analysis, RFS after nephrectomy was significantly shorter in patients aged <70 years, symptomatic at presentation, with larger tumours, higher nuclear grade, collecting-system invasion, and/or sarcomatoid differentiation. After multivariate analysis, T-stage, nuclear grade and sarcomatoid differentiation retained their power as independent predictors of RFS (P = 0.032, <0.001 and 0.003, respectively). Conclusions For patients with LARCC, T-stage, grade and sarcomatoid differentiation independently dictate the

  10. [A Case of Complete Pathological Response in a Patient with Locally Advanced Sigmoid Colon Cancer after FOLFOX IRI Chemotherapy].

    PubMed

    Goto, Masakazu; Okitsu, Hiroshi; Yuasa, Yasuhiro; Matsuo, Yuta; Edagawa, Hiroshi; Tani, Ryotaro; Mori, Osamu; Kuramoto, Shunsuke; Tomibayashi, Atsushi; Yamashita, Michiko; Fujii, Yoshiyuki

    2015-11-01

    A 61-year-old man with advanced sigmoid colon cancer was admitted to our hospital. Abdominal computed tomography (CT) revealed locally advanced sigmoid colon cancer, with suspected invasion of the bladder and small intestine. The clinical stage of the disease was T4b, N1, M0, and Stage III a, with wild-type KRAS expression. A transverse colostomy was performed because of the presence of a bowel obstruction. The patient received 4 courses of Leucovorin, 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI). The size of the tumor and lymph nodes decreased noticeably after chemotherapy and laparoscopic high anterior resection with lymph node dissection. During this phase, the pathological stage of the disease was ypT0, N0, and Stage 0(no viable carcinoma cells, Grade 3). This result suggested that preoperative FOLFOXIRI chemotherapy is a useful regimen for the treatment of locally advanced colon cancer. PMID:26602406

  11. Current update on combined hepatocellular-cholangiocarcinoma

    PubMed Central

    Maximin, Suresh; Ganeshan, Dhakshina Moorthy; Shanbhogue, Alampady K.; Dighe, Manjiri K.; Yeh, Matthew M.; Kolokythas, Orpheus; Bhargava, Puneet; Lalwani, Neeraj

    2014-01-01

    Combined hepatocellular-cholangiocarcinoma is a rare but unique primary hepatic tumor with characteristic histology and tumor biology. Recent development in genetics and molecular biology support the fact that combined hepatocellular-cholangiocarcinoma is closely linked with cholangiocarcinoma, rather than hepatocellular carcinoma. Combined hepatocellular cholangiocarcinoma tends to present with an more aggressive behavior and a poorer prognosis than either hepatocellular carcinoma or cholangiocarcinoma. An accurate preoperative diagnosis and aggressive treatment planning can play crucial roles in appropriate patient management. PMID:26937426

  12. Advancing the use of local ecological knowledge for assessing data-poor species in coastal ecosystems.

    PubMed

    Beaudreau, Anne H; Levin, Phillip S

    2014-03-01

    Many of the world's most vulnerable and rapidly changing ecosystems are also among the most data-poor, leading to an increased interest in use of local ecological knowledge (LEK) to document long-term environmental change. The integration of multiple knowledge sources for assessing species abundance and distribution has gained traction over the past decade as a growing number of case studies show concordance between LEK and scientific data. This study advances the use of quantitative approaches for synthesizing LEK by presenting a novel application of bootstrapping and statistical modeling to evaluate variance in ecological observations of fisheries practitioners. We developed an historical record of abundance for 22 marine species in Puget Sound, Washington (USA), using LEK, and we quantified variation in perceptions of abundance trends among fishers, divers, and researchers. These individuals differed in aspects of their information environments, which are characterized by how, when, and where an individual has acquired ecological information. Abundance trends derived from interviews suggest that populations of long-lived rockfishes (Sebastes spp.) have been in decline since at least the 1960s and that three rockfishes protected under the Endangered Species Act were perceived as relatively less abundant than other species. Differences in perception of rockfish abundance trends among age groups were consistent with our hypothesis that the reported magnitude of decline in abundance would increase with age, with younger respondents more likely to report high abundance than older individuals across all periods. Temporal patterns in the mean and variance of reported rockfish abundance indices were qualitatively similar between fishers and researchers; however, fishers reported higher indices of abundance than researchers for all but one rockfish species. The two respondent groups reported similar changes in rockfish abundance from the 1940s to 2000s, except for two

  13. Treatment of hepatocellular carcinoma: beyond international guidelines.

    PubMed

    Colombo, Massimo; Sangiovanni, Angelo

    2015-01-01

    The management of hepatocellular carcinoma (HCC) is decided according to evidence-based recommendations generated by international societies: according to these recommendations, the tumour stage, as determined by the Barcelona clinical liver cancer (BCLC) score, divides patients into five prognostic categories, each with a distinct treatment indication. Radical therapies such as hepatic resection, orthotopic liver transplantation and percutaneous local ablation are strongly indicated in patients with very early and early stage tumours (BCLC O and A), a choice which mainly depends on a combination of tumour volume, status of underlying liver disease, the presence of comorbidities and the patient's age. Although radical therapies provide a survival rate of between 50% and 75% at year five in well selected patients, tumour recurrence is frequent following resection and ablation compared to transplantation (70% vs. 10% respectively), which has the additional advantage of preventing morbidity and mortality from portal hypertension. Generally, while radical therapies are contraindicated in patients with a large tumour burden, such as those with intermediate stage BCLC B, survival in the subset of these patients with well compensated cirrhosis may improve from 16 to 20 months, on average, following repeated treatments with transarterial chemoembolization (TACE). Survival may also improve in patients who are in poor condition or who do not respond to TACE and in those with an advanced HCC (BCLC C) following oral therapy with the multikinase inhibitor sorafenib. However, because most recommendations are based on uncontrolled studies and expert opinions rather than well designed, high powered randomized controlled trials, treatment criteria need to be adapted to special groups because real life cohorts do not match the selection criteria suggested by the guidelines. Indeed, up to one-third of patients with early stage tumours who are unfit for radical therapy because of

  14. Cell Based Autologous Immune Enhancement Therapy (AIET) after Radiotherapy in a Locally Advanced Carcinoma of the Cervix

    PubMed Central

    Premkumar, Sumana; Dedeepiya, Vidyasagar Devaprasad; Terunuma, Hiroshi; Senthilkumar, Rajappa; Srinivasan, Thangavelu; Reena, Helen C.; Preethy, Senthilkumar; Abraham, Samuel J. K.

    2013-01-01

    Radiotherapy is the primary form of treatment in patients with locally advanced cervical carcinoma. However for residual disease in the form of the persistent lymph nodes, surgery or chemotherapy is recommended. As surgery is not acceptable by every patient and chemotherapy has associated side effects, we hereby report the positive outcome of in vitro expanded natural killer cell and activated T lymphocyte based autologous immune enhancement therapy (AIET) for the residual lymphadenopathy in a patient with locally advanced cervical cancer after radiation. After six transfusions of AIET, there was complete resolution of residual lymph nodes and there was no evidence of local lesion. The patient also reported improvement in quality of life. As AIET has been reported as the least toxic among the available therapies for cancer, combining AIET with conventional forms of therapy in similar patients might not only improve the outcome but may also help the patients achieve a good quality of life. PMID:23653878

  15. Implementation status of the global and local beam position feedback systems for the Advanced Photon Source storage ring

    SciTech Connect

    Chung, Y.; Barr, D.; Decker, G.; Galayda, J.; Kirchman, J.; Lenkszus, F.; Lumpkin, A.; Votaw, A.J.

    1995-07-01

    The Advanced Photon Source (APS) is implementing an extensive beam position feedback system for both global and local stabilization of particle and photon beams based on digital signal processing. The description and operational experience of the system will be given in this paper. In particular, we will discuss the underlying fundamental principles, hardware layout, controls interface, and automatic software generation for multiple digital signal processors (DSPS) distributed in 20 VME crates around the ring. The feedback system runs at 4-kHz sampling frequency in order to achieve the correction bandwidth of approximately 100 Hz. For the maximum correction efficiency and resolution of conflicts among multiple local feedback systems due to the local bump closure error, the global and local feedback systems are combined into a single unified system. This novel approach is made possible through data sharing among the global and local systems via the fiber-optically networked reflective memories.

  16. High-Intensity Focused Ultrasound for the Treatment of Localized and Locally Advanced Hormone-Resistant Prostate Cancer: 2,5 Year Outcome

    NASA Astrophysics Data System (ADS)

    Solovov, V. A.; Dvoynikov, S. Y.; Vozdvizhenskiy, M. O.

    2011-09-01

    Introduction & Objectives: High-Intensity Focused Ultrasound (HIFU) has been shown to be a successful treatment for localised prostate cancer (PC). Here we have explored the effectiveness of the HIFU treatment for hormone-resistant prostate cancer (HRPC). Materials & Methods: 341 patients were treated in our center between September 2007 and December 2009; all of them showed treatment failure following hormone ablation. The median time before hormone-resistance was 20 (3-48) months. In the group with localised PC: number of patients 237, Gleason score ≤7, stage T1-2N0M0, age 69 (60-89) years, mean PSA before treatment 40,0 (5,8-92,9) ng/ml, mean prostate volume—39,3 (28-92) cc; in the group with locally advanced PC: number of patients 104, Gleason score ≤9, stage T2-3N0M0, age 72 (52-83) years, PSA before treatment 30,3 (20,1-60) ng/ml, mean prostate volume—41,2 (25-198) cc. HIFU was delivered under spinal anesthesia using the Ablatherm HIFU device (EDAP, France). Pre HIFU transurethral resection of the prostate (TURP) was performed for all patients. Mean follow-up time 18 months (3-30). Results: The median PSA level 12 months after HIFU treatment was 0,04 (0-2,24) ng/ml—localised PC, and for locally advanced disease—0,05 (0-48,4) ng/ml, at 18 months after HIFU treatment this was 0,2 (0,02-2,0) ng/ml for localised PC, and for locally advanced disease 0,18 (0,04-7,45) ng/ml. Patients with localised PC has 4,5% recurrence, those with locally advanced PC 20%. Kaplan-Meir analyses of the total group indicated that the risk of recurrence after 1 year follow-up was 10%, the risk of recurrence was 19% after 2 years of follow-up. Conclusions: Our initial experience shows that ultrasound ablation is safe, minimally invasive and effective as a treatment for localised and locally advanced hormone-resistant prostate cancer.

  17. Simultaneous integrated intensity-modulated radiotherapy boost for locally advanced gynecological cancer: Radiobiological and dosimetric considerations

    SciTech Connect

    Guerrero, Mariana; Li, X. Allen . E-mail: ali@radonc.mcw.edu; Ma Lijun; Linder, Jeanette; Deyoung, Chad; Erickson, Beth

    2005-07-01

    Purpose: Whole-pelvis irradiation (WPI) followed by a boost to the tumor site is the standard of practice for the radiotherapeutic management of locally advanced gynecologic cancers. The boost is frequently administered by use of brachytherapy or, occasionally, external-beam radiotherapy (EBRT) when brachytherapy does not provide sufficient coverage because of the size of the tumor or the geometry of the patient. In this work, we propose using an intensity-modulated radiotherapy (IMRT) simultaneous integrated boost (SIB), which is a single-phase process, to replace the conventional two-phase process involving WPI plus a boost. Radiobiological modeling is used to design appropriate regimens for the IMRT SIB. To demonstrate feasibility, a dosimetric study is carried out on an example patient. Methods and Materials: The standard linear-quadratic (LQ) model is used to calculate the biologically effective dose (BED) and equivalent uniform dose (EUD). A series of regimens that are biologically equivalent to those conventional two-phase treatments is calculated for the proposed SIB. A commercial inverse planning system (Corvus) was used to generate IMRT SIB plans for a sample patient case that used the newly designed fractionations. The dose-volume histogram (DVH) and EUD of both the target and normal structures for conventional treatments and the SIB are compared. A sparing factor was introduced to characterize the sparing of normal structures. Results: Fractionation regimes that are equivalent to the conventional treatments and are suitable for the IMRT SIB are deduced. For example, a SIB plan with 25 x 3.1 Gy (77.5 Gy) to a tumor is equivalent to a conventional treatment of EBRT of 45 Gy to the whole pelvis in 25 fractions plus a high-dose rate (HDR) brachytherapy boost with 30 Gy in 5 fractions. The normal tissue BED is found to be lower for the SIB plan than for the whole-pelvis plus HDR scheme when a sparing factor for the critical structures is considered. This

  18. Pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer.

    PubMed

    Greenhalgh, J; McLeod, C; Bagust, A; Boland, A; Fleeman, N; Dundar, Y; Oyee, J; Dickson, R; Davis, H; Green, J; McKenna, E; Pearson, M

    2010-10-01

    This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of pemetrexed for the maintenance treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC), in accordance with the licensed indication, based upon the evidence submission from the manufacturer (Eli Lilly) to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The primary clinical outcome measure was progression free survival (PFS). Secondary outcomes included overall survival (OS), time to worsening of symptoms, objective tumour response rate, adverse events and changes in lung cancer symptom scale. Data for two populations were presented: patients with non-squamous NSCLC histology and patients with adenocarcinoma histology. The clinical evidence was derived from a double-blind, placebo-controlled randomised controlled trial (RCT), the JMEN trial. The trial compared the use of pemetrexed + best supportive care (BSC ) as maintenance therapy, with placebo + BSC in patients with NSCLC (n = 663) who had received four cycles of platinum-based chemotherapy (CTX) and whose disease had not progressed. In the licensed population (patients with non-squamous histology), the trial demonstrated greater median PFS for patients treated with pemetrexed than for patients in the placebo arm [4.5 vs 2.6 months; hazard ratio (HR) 0.44; 95% confidence interval (CI) 0.36 to 0.55, p < 0.00001]. Median OS was also greater for the pemetrexed- treated patients (15.5 vs 10.3 months; HR 0.70; 95% CI 0.56 to 0.88, p = 0.002). In addition, tumour response and disease control rates were statistically significantly greater for patients who received pemetrexed. Patient survival rates at 1 year and 2 years were higher in the pemetrexed arm. The incremental cost-effectiveness ratios (ICERs) estimated by the manufacturer's model were 33,732 pounds per quality adjusted life-year (QALY

  19. Radiation induced apoptosis and initial DNA damage are inversely related in locally advanced breast cancer patients

    PubMed Central

    2010-01-01

    Background DNA-damage assays, quantifying the initial number of DNA double-strand breaks induced by radiation, have been proposed as a predictive test for radiation-induced toxicity. Determination of radiation-induced apoptosis in peripheral blood lymphocytes by flow cytometry analysis has also been proposed as an approach for predicting normal tissue responses following radiotherapy. The aim of the present study was to explore the association between initial DNA damage, estimated by the number of double-strand breaks induced by a given radiation dose, and the radio-induced apoptosis rates observed. Methods Peripheral blood lymphocytes were taken from 26 consecutive patients with locally advanced breast carcinoma. Radiosensitivity of lymphocytes was quantified as the initial number of DNA double-strand breaks induced per Gy and per DNA unit (200 Mbp). Radio-induced apoptosis at 1, 2 and 8 Gy was measured by flow cytometry using annexin V/propidium iodide. Results Radiation-induced apoptosis increased in order to radiation dose and data fitted to a semi logarithmic mathematical model. A positive correlation was found among radio-induced apoptosis values at different radiation doses: 1, 2 and 8 Gy (p < 0.0001 in all cases). Mean DSB/Gy/DNA unit obtained was 1.70 ± 0.83 (range 0.63-4.08; median, 1.46). A statistically significant inverse correlation was found between initial damage to DNA and radio-induced apoptosis at 1 Gy (p = 0.034). A trend toward 2 Gy (p = 0.057) and 8 Gy (p = 0.067) was observed after 24 hours of incubation. Conclusions An inverse association was observed for the first time between these variables, both considered as predictive factors to radiation toxicity. PMID:20868468

  20. Response monitoring using quantitative ultrasound methods and supervised dictionary learning in locally advanced breast cancer

    NASA Astrophysics Data System (ADS)

    Gangeh, Mehrdad J.; Fung, Brandon; Tadayyon, Hadi; Tran, William T.; Czarnota, Gregory J.

    2016-03-01

    A non-invasive computer-aided-theragnosis (CAT) system was developed for the early assessment of responses to neoadjuvant chemotherapy in patients with locally advanced breast cancer. The CAT system was based on quantitative ultrasound spectroscopy methods comprising several modules including feature extraction, a metric to measure the dissimilarity between "pre-" and "mid-treatment" scans, and a supervised learning algorithm for the classification of patients to responders/non-responders. One major requirement for the successful design of a high-performance CAT system is to accurately measure the changes in parametric maps before treatment onset and during the course of treatment. To this end, a unified framework based on Hilbert-Schmidt independence criterion (HSIC) was used for the design of feature extraction from parametric maps and the dissimilarity measure between the "pre-" and "mid-treatment" scans. For the feature extraction, HSIC was used to design a supervised dictionary learning (SDL) method by maximizing the dependency between the scans taken from "pre-" and "mid-treatment" with "dummy labels" given to the scans. For the dissimilarity measure, an HSIC-based metric was employed to effectively measure the changes in parametric maps as an indication of treatment effectiveness. The HSIC-based feature extraction and dissimilarity measure used a kernel function to nonlinearly transform input vectors into a higher dimensional feature space and computed the population means in the new space, where enhanced group separability was ideally obtained. The results of the classification using the developed CAT system indicated an improvement of performance compared to a CAT system with basic features using histogram of intensity.

  1. Cost-effectiveness of para-aortic lymphadenectomy before chemoradiotherapy in locally advanced cervical cancer

    PubMed Central

    Lee, Jung-Yun; Kim, Younhee; Lee, Tae-Jin; Jeon, Yong Woo; Kim, Kidong; Chung, Hyun Hoon; Park, Sang Min; Kim, Jae-Weon

    2015-01-01

    Objective To evaluate the cost-effectiveness of nodal staging surgery before chemoradiotherapy (CRT) for locally advanced cervical cancer in the era of positron emission tomography/computed tomography (PET/CT). Methods A modified Markov model was constructed to evaluate the cost-effectiveness of para-aortic staging surgery before definite CRT when no uptake is recorded in the para-aortic lymph nodes (PALN) on PET/CT. Survival and complication rates were estimated based on the published literature. Cost data were obtained from the Korean Health Insurance Review and Assessment Service. Strategies were compared using an incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed, including estimates for the performance of PET/CT, postoperative complication rate, and varying survival rates according to the radiation field. Results We compared two strategies: strategy 1, pelvic CRT for all patients; and strategy 2, nodal staging surgery followed by extended-field CRT when PALN metastasis was found and pelvic CRT otherwise. The ICER for strategy 2 compared to strategy 1 was $19,505 per quality-adjusted life year (QALY). Under deterministic sensitivity analyses, the model was relatively sensitive to survival reduction in patients who undergo pelvic CRT alone despite having occult PALN metastasis. A probabilistic sensitivity analysis demonstrated the robustness of the case results, with a 91% probability of cost-effectiveness at the willingness-to-pay thresholds of $60,000/QALY. Conclusion Nodal staging surgery before definite CRT may be cost-effective when PET/CT imaging shows no evidence of PALN metastasis. Prospective trials are warranted to transfer these results to guidelines. PMID:25925292

  2. Intraoperative Radiotherapy During Radical Prostatectomy for Locally Advanced Prostate Cancer: Technical and Dosimetric Aspects

    SciTech Connect

    Krengli, Marco; Terrone, Carlo; Ballare, Andrea; Loi, Gianfranco; Tarabuzzi, Roberto; Marchioro, Giansilvio; Beldi, Debora; Mones, Eleonora; Bolchini, Cesare R.T.; Volpe, Alessandro; Frea, Bruno

    2010-03-15

    Purpose: To analyze the feasibility of intraoperative radiotherapy (IORT) in patients with high-risk prostate cancer and candidates for radical prostatectomy. Methods and Materials: A total of 38 patients with locally advanced prostate cancer were enrolled. No patients had evidence of lymph node or distant metastases, probability of organ-confined disease >25%, or risk of lymph node involvement >15% according to the Memorial Sloan-Kettering Cancer Center Nomogram. The IORT was delivered after exposure of the prostate by a dedicated linear accelerator with beveled collimators using electrons of 9 to 12 MeV to a total dose of 10-12 Gy. Rectal dose was measured in vivo by radiochromic films placed on a rectal probe. Administration of IORT was followed by completion of radical prostatectomy and regional lymph node dissection. All cases with extracapsular extension and/or positive margins were scheduled for postoperative radiotherapy. Patients with pT3 to pT4 disease or positive nodes received adjuvant hormonal therapy. Results: Mean dose detected by radiochromic films was 3.9 Gy (range, 0.4-8.9 Gy) to the anterior rectal wall. The IORT procedure lasted 31 min on average (range, 15-45 min). No major intra- or postoperative complications occurred. Minor complications were observed in 10/33 (30%) of cases. Of the 27/31 patients who completed the postoperative external beam radiotherapy, 3/27 experienced Grade 2 rectal toxicity and 1/27 experienced Grade 2 urinary toxicity. Conclusions: Use of IORT during radical prostatectomy is feasible and allows safe delivery of postoperative external beam radiotherapy to the tumor bed without relevant acute rectal toxicity.

  3. Phase I study of conformal radiotherapy with concurrent gemcitabine in locally advanced bladder cancer

    SciTech Connect

    Sangar, Vijay K.; McBain, Catherine A.; Lyons, Jeanette; Ramani, Vijay; Logue, John; Wylie, James; Clarke, Noel W.; Cowan, Richard A. . E-mail: richard.cowan@christie-tr.nwest.nhs.uk

    2005-02-01

    Purpose: A prospective phase I trial was conducted to determine the maximal tolerated dose of gemcitabine given once weekly during hypofractionated conformal radiotherapy to patients with locally advanced transitional cell carcinoma of the bladder. Eight male patients, median age 69 years, with Stage T2 (n = 4) or T3 (n = 4) N0M0, were enrolled in cohorts of 3. Treatment comprised conformal radiotherapy (52.5 Gy in 20 fractions) within 4 weeks, with concurrent gemcitabine once weekly for four cycles. The weekly gemcitabine dose was escalated from 100 mg/m{sup 2} in increments of 50 mg/m{sup 2} per cohort. Dose-limiting toxicity was defined as any acute Radiation Therapy Oncology Group (RTOG) toxicity Grade 3 or greater arising in >1 of 3 patients in each cohort. Tumor response was assessed cystoscopically and radiologically at 3 months. Results: All 8 patients completed radiotherapy, and 6 of 8 completed chemoradiotherapy. No acute toxicity greater than RTOG Grade 1 was seen with gemcitabine at 100 mg/m{sup 2}. Dose-limiting toxicity was observed at 150 mg/m{sup 2} with Grade 3 toxicity seen in 2 of 2 patients (one bladder, one bowel). An additional 3 patients received 100 mg/m{sup 2} with minimal toxicity. No hematologic toxicity was encountered. A complete response was seen in 7 (87.5%) of 8 patients, all of whom were disease free at a median follow-up of 19.5 months (range, 14-23 months). No late toxicity (greater than RTOG Grade 0) has been observed. Conclusion: The maximal tolerated dose for gemcitabine given once weekly with concurrent hypofractionated conformal bladder radiotherapy was 150 mg/m{sup 2}, with a maximal recommended dose of 100 mg/m{sup 2}. This dose regimen has now entered Phase II clinical trials.

  4. Chemotherapy and irradiation for locally advanced and metastatic pulmonary carcinoid tumors

    PubMed Central

    Chong, Curtis R.; Wirth, Lori J.; Nishino, Mizuki; Chen, Aileen B.; Sholl, Lynette M.; Kulke, Matthew H.; McNamee, Ciaran J.; Jänne, Pasi A.; Johnson, Bruce E.

    2015-01-01

    Objectives The optimal management of locally advanced and metastatic pulmonary carcinoid tumors remains to be determined. Materials and methods A retrospective review was conducted on patients with typical and atypical pulmonary carcinoid tumors treated at our institutions between 1990 and 2012. Results 300 patients were identified with pulmonary carcinoid, (80 patients with atypical carcinoid), of whom 29 presented with metastatic disease (16 atypical). Of evaluable patients, 26 (41%) with stages I–III atypical carcinoid tumors recurred at a median time of 3.7 years (range, 0.4–32), compared to 3 (1%) patients with typical carcinoid (range, 8–12.3). 39 patients were treated with chemotherapy, including 30 patients with metastatic disease (27 atypical), and 7 patients were treated with adjuvant platinum–etoposide chemoradiation (6 atypical, 1 typical, 6 stage IIIA, 1 stage IIB). At a median follow-up of 2 years there were 2 recurrences in the 7 patients receiving adjuvant treatment. Median survival after diagnosis of metastatic disease for patients with atypical pulmonary carcinoid was 3.3 years with a 5-year survival of 24%. Treatment regimens showing efficacy in pulmonary carcinoid include 15 patients treated with octreotide-based therapies (10% response rate (RR), 70% disease control rate (DCR), 15 month median progression-free survival (PFS)), 13 patients treated with etoposide + platinum (23% RR, 69% DCR, 7 month median PFS), and 14 patients treated with temozolomide-based therapies (14% RR, 57% DCR, 10 month median PFS). 8 of 10 patients with octreotide-avid disease treated with an octreotide-based regimen experienced disease control (1 partial response, 7 stable disease) for a median of 18 months (range 6–72 months). Conclusions These results support our previous finding that a subset of pulmonary carcinoid tumors are responsive to chemotherapy. PMID:25218177

  5. Phase I Study of Daily Irinotecan as a Radiation Sensitizer for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Fouchardiere, Christelle de la; Negrier, Sylvie; Labrosse, Hugues; Martel Lafay, Isabelle; Desseigne, Francoise; Meeus, Pierre; Tavan, David; Petit-Laurent, Fabien; Rivoire, Michel; Perol, David; Carrie, Christian

    2010-06-01

    Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unresectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m{sup 2} per day and then escalated by increments of 2 mg/m{sup 2} every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperability was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m{sup 2} to 20 mg/m{sup 2} per day). The maximum tolerated dose was determined to be 18 mg/m{sup 2} per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m{sup 2} per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.

  6. Role of plasma osteopontin as a biomarker in locally advanced breast cancer

    PubMed Central

    Anborgh, Pieter H; Caria, Laura BR; Chambers, Ann F; Tuck, Alan B; Stitt, Larry W; Brackstone, Muriel

    2015-01-01

    Osteopontin (OPN), a malignancy-associated secreted phosphoprotein, is a prognostic plasma biomarker for survival in metastatic breast cancer patients. We evaluated the role of OPN in Locally Advanced Breast Cancer (LABC) patients in predicting response to neoadjuvant chemotherapy and association with survival. Fifty-three patients with non-metastatic LABC were enrolled in this study and monitored serially for plasma OPN levels by ELISA during neoadjuvant chemotherapy prior to surgery. For fifty patients who had baseline OPN levels available for analysis, the median baseline OPN level was 63.6 ng/ml. Median patient follow up was 45 months and thirteen patients died from metastatic disease. Patients with baseline OPN levels ≥ 63.6 ng/ml were significantly more likely to die of their disease than those with baseline OPN < 63.6 ng/mL (Hazard Ratio = 3.4; 95% confidence interval 1.4-11.3; P = 0.011), and overall, baseline OPN level was significantly associated with survival (P = 0.002). There was little support for value of serial OPN determination in monitoring response to therapy in this patient population. Although the percentage of patients with baseline OPN levels < 63.6 ng/ml was higher in patients with pathological complete response than in those with no response, the difference was not statistically significant (64% and 14%, respectively (P = 0.066)). Thus, baseline plasma OPN level is a prognostic biomarker in this group of LABC patients, and could also be helpful in identifying LABC patients who will respond to neoadjuvant chemotherapy. Our results call for validation of our findings in large prospective trial data sets. PMID:26064440

  7. Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

    SciTech Connect

    Zampino, Maria Giulia Magni, Elena; Leonardi, Maria Cristina; Petazzi, Elena; Santoro, Luigi; Luca, Fabrizio; Chiappa, Antonio; Petralia, Giuseppe; Trovato, Cristina; Fazio, Nicola; Orecchia, Roberto; Nole, Franco; Braud, Filippo de

    2009-10-01

    Purpose: To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). Methods and Materials: From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m{sup 2}, orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m{sup 2}, orally, twice daily, 14 days on 7 days off) up until 2 weeks before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. Results: Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors {<=}6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). Conclusions: Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.

  8. Initial Staging of Locally Advanced Rectal Cancer and Regional Lymph Nodes

    PubMed Central

    Cerny, Milena; Dunet, Vincent; Prior, John Olivier; Hahnloser, Dieter; Wagner, Anna Dorothea; Meuli, Reto Antoine; Schmidt, Sabine

    2016-01-01

    Purpose The aim of the study was to compare diffusion-weighted MRI (DW-MRI) parameters with 18F-FDG PET/CT in primary locally advanced rectal cancer (LARC). Methods From October 2012 to September 2014, 24 patients with histologically confirmed and untreated LARC (T3–T4) prospectively underwent a pelvic 1.5-T DW-MRI (b = 0 s/mm2, b = 600 s/mm2) and a whole-body 18F-FDG PET/CT, before neoadjuvant therapy. The 2 examinations were performed on the same day. Two readers measured 18F-FDG SUVmax and SUVmean of the rectal tumor and of the pathological regional lymph nodes on PET/CT and compared these with minimum and mean values of the ADC (ADCmin and ADCmean) on maps generated from DW-MRI. The diagnostic performance of ADC values in identifying pathological lymph nodes was also assessed. Results Regarding tumors (n = 24), we found a significant negative correlation between SUVmean and corresponding ADCmean values (ρ = −0.61, P = 0.0017) and between ADCmin and SUVmax (ρ = −0.66, P = 0.0005). Regarding the lymph nodes (n = 63), there was a significant negative correlation between ADCmean and SUVmean values (ρ = −0.38, P = 0.0021), but not between ADCmin and SUVmax values (ρ = −0.11, P = 0.41). Neither ADCmean nor ADCmin values helped distinguish pathological from benign lymph nodes (AUC of 0.24 [confidence interval, 0.10–0.38] and 0.41 [confidence interval, 0.22–0.60], respectively). Conclusions The correlations between ADCmean and SUVmean suggest an association between tumor cellularity and metabolic activity in untreated LARC and in regional lymph nodes. However, compared with 18F-FDG PET/CT, ADC values are not reliable for identifying pathological lymph nodes. PMID:26828149

  9. RNAi therapy targeting KRAS in combination with chemotherapy for locally advanced pancreatic cancer patients

    PubMed Central

    Golan, Talia; Khvalevsky, Elina Zorde; Hubert, Ayala; Gabai, Rachel Malka; Hen, Naama; Segal, Amiel; Domb, Abraham; Harari, Gil; David, Eliel Ben; Raskin, Stephen; Goldes, Yuri; Goldin, Eran; Eliakim, Rami; Lahav, Maor; Kopleman, Yael; Dancour, Alain; Shemi, Amotz; Galun, Eithan

    2015-01-01

    Purpose The miniature biodegradable implant siG12D-LODER™ was inserted into a tumor and released a siRNA drug against KRAS(G12D) along four months. This novel siRNA based drug was studied, in combination with chemotherapy, as targeted therapy for Locally Advanced Pancreatic Cancer (LAPC). Methods An open-label Phase 1/2a study in the first-line setting of patients with non-operable LAPC was initiated. In this study patients were assigned to receive a single dose of siG12D-LODERs, in three escalating dose cohorts (0.025mg, 0.75mg and 3.0mg). Gemcitabine was given on a weekly basis, following the siG12D-LODERTM insertion, until disease progression. The recommended dose was further examined with modified FOLFIRINOX. The follow up period was eight weeks and survival until death. Results Fifteen patients with LAPC were enrolled. Among the 15 treated patients, the most frequent adverse events observed were grade 1or 2 in severity (89%); five patients experienced serious adverse events (SAEs). In 12 patients analyzed by CT scans, none showed tumor progression, the majority (10/12) demonstrated stable disease and two showed partial response. Decrease in tumor marker CA19-9 was observed in 70% (7/10) of patients. Median overall survival was 15.12 months; 18 month survival was 38.5%. Conclusions The combination of siG12D-LODER™ and chemotherapy is well tolerated, safe and demonstrated a potential efficacy in patients with LAPC. NCT01188785 PMID:26009994

  10. Long-Term Survival and Local Relapse Following Surgery Without Radiotherapy for Locally Advanced Upper Rectal Cancer

    PubMed Central

    Park, Jun Seok; Sakai, Yoshiharu; Simon, NG Siu Man; Law, Wai Lun; Kim, Hyeong Rok; Oh, Jae Hwan; Shan, Hester Cheung Yui; Kwak, Sang Gyu; Choi, Gyu-Seog

    2016-01-01

    Abstract Controversy remains regarding whether preoperative chemoradiation protocol should be applied uniformly to all rectal cancer patients regardless of tumor height. This pooled analysis was designed to evaluate whether preoperative chemoradiation can be safely omitted in higher rectal cancer. An international consortium of 7 institutions was established. A review of the database that was collected from January 2004 to May 2008 identified a series of 2102 patients with stage II/III rectal or sigmoid cancer (control arm) without concurrent chemoradiation. Data regarding patient demographics, recurrence pattern, and oncological outcomes were analyzed. The primary end point was the 5-year local recurrence rate. The local relapse rate of the sigmoid colon cancer (SC) and upper rectal cancer (UR) cohorts was significantly lower than that of the mid/low rectal cancer group (M-LR), with 5-year estimates of 2.5% for the SC group, 3.5% for the UR group, and 11.1% for the M-LR group, respectively. A multivariate analysis showed that tumor depth, nodal metastasis, venous invasion, and lower tumor level were strongly associated with local recurrence. The cumulative incidence rate of local failure was 90.6%, 92.5%, and 94.4% for tumors located within 5, 7, and 9 cm from the anal verge, respectively. Routine use of preoperative chemoradiation for stage II/III rectal tumors located more than 8 to 9 cm above the anal verge would be excessive. The integration of a more individualized approach focused on systemic control is warranted to improve survival in patients with upper rectal cancer. PMID:27258487

  11. Radiofrequency ablation for hepatocellular carcinoma.

    PubMed

    Nishikawa, Hiroki; Kimura, Toru; Kita, Ryuichi; Osaki, Yukio

    2013-09-01

    Hepatocellular carcinoma (HCC) is one of the most common causes of cancer-related mortality worldwide. Unfortunately, only 20% of HCC patients are amenable to curative therapy (liver transplantation or surgical resection). Locoregional therapies such as radiofrequency ablation (RFA), percutaneous ethanol injection, microwave coagulation therapy, and transcatheter arterial chemoembolisation play a key role in the management of HCC. The choice of the treatment modality depends on the size of the tumour, tumour location, anatomic considerations and the number of tumours present and liver function. RFA therapy for HCC can be performed safely using a percutaneous, laparoscopic, or an open approach, even in patients with poor functional reserve. Since the introduction of RFA, several randomised controlled trials and non-randomised studies comparing RFA and other therapies for HCC have been conducted. In addition, in the last decade there have been technical advances in RFA therapy for HCC, resulting in significant improvement in the prognosis of HCC patients treated with this modality. In this review, we primarily focus on percutaneous RFA therapy for HCC and refer to current knowledge and future perspectives for this therapy. We also discuss new emerging ablation techniques. PMID:23937321

  12. Liver transplantation for hepatocellular carcinoma.

    PubMed

    Sarpel, Umut; Schwartz, Myron

    2007-09-01

    Hepatocellular carcinoma can only be cured by physical removal or destruction of the tumor before it has spread. This can be accomplished by the ablation of the tumor, surgical resection of the tumor-bearing liver, or by liver transplantation. Ablation and resection can only be performed in patients who will be left with sufficient liver volume to sustain normal hepatic function. Unfortunately, the same disease that caused the HCC also limits the amount of parenchymal loss that can be tolerated by the patient. Liver transplantation is an appealing treatment option because it has the potential to cure patient of both the cancer and the predisposinig liver disease. Excellent survival rates are possible in patients with early HCC who receive a transplant, but dismal results are seen when patients with advanced tumors are transplanted.Wide criteria for transplant allow for more patients to be cured of HCC, but this comes at the expense of a greater overall recurrence rate. The acceptable recurrence rate is not a concrete number, but this is a function of donor organ availability. A 50% cure rate is viewed as an excellent outcome for many accepted cancer operations; however, in the case of transplant for HCC, this would represent a poor use of the scarce donor resource when the same liver offers a 70% 5-year survival rate to a non-HCC patient. These issues and methods retarding tumor progression while on the transplant waiting list are reviewed herein. PMID:17877492

  13. Neoadjuvant chemoradiotherapy followed by D2 gastrectomy in locally advanced gastric cancer

    PubMed Central

    Kim, Mi Sun; Lim, Joon Seok; Hyung, Woo Jin; Lee, Yong Chan; Rha, Sun Young; Keum, Ki Chang; Koom, Woong Sub

    2015-01-01

    AIM: To investigate the efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectability of locally advanced gastric cancer (LAGC). METHODS: Between November 2007 and January 2014, 29 patients with LAGC (clinically T3 with distal esophagus invasion/T4 or bulky regional node metastasis) that were treated with NACRT followed by D2 gastrectomy were included in this study. Resectability was evaluated with radiologic and endoscopic exams before and after NACRT. Using three-dimensional conformal radiotherapy, patients received 45 Gy, with a daily dose of 1.8 Gy. The entire tumor extent and the regional metastatic lymph nodes were included in the gross tumor volume. Patients presenting with a resectable tumor after NACRT received a total or subtotal gastrectomy with D2 dissection. The pathologic tumor response was evaluated using Japanese Gastric Cancer Association histologic evaluation criteria. Postoperative morbidity was evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and progression-free survival (PFS) rates were estimated using a Kaplan-Meier analysis and compared using the log-rank test. RESULTS: All patients were assessed as unresectable cases. Twenty-four patients (24/29; 82.8%) showed LAGC on positron emission tomography-computed tomography (CT) and contrast-enhanced CT, whereas four patients (4/29; 13.8%) with vague invasion or abutment to an adjacent organ underwent diagnostic laparoscopy. One patient (1/29; 3.4%), initially assessed as a resectable case, underwent an “open and closure” after the tumor was found to be unresectable. Abutment to an adjacent organ (34.5%) was the most common reason for NACRT. The clinical response rate one month after NACRT was 44.8%. After NACRT, 69% (20/29) of patients had a resectable tumor. Of the 20 patients with a resectable tumor, 18 patients (62.1%) underwent a D2 gastrectomy. The R0 resection rate was 94.4% and two patients (2/18; 11

  14. Fulminant hepatitis in a patient with hepatocellular carcinoma related to nonalcoholic steatohepatitis treated with sorafenib.

    PubMed

    Brandi, Giovanni; De Lorenzo, Stefania; Di Girolamo, Stefania; Bellentani, Stefano; Saccoccio, Gioconda; Biasco, Guido

    2015-01-01

    We describe a case of acute liver failure in a patient with advanced hepatocellular carcinoma related to nonalcoholic steatohepatitis during sorafenib treatment. A 74-year-old man with diabetes mellitus and hypertension was diagnosed with hepatocellular carcinoma associated with fatty liver. Three weeks after sorafenib therapy, at Eastern Cooperative Oncology Group performance status 3, he developed jaundice, general weakness, flapping tremor, nausea, and anorexia. Sorafenib was stopped: laboratory tests showed a relevant elevation of transaminases suggesting diagnosis of acute hepatitis. During hospital admission, the patient died of liver failure. Sorafenib is the first successful target therapy effective for advanced hepatocellular carcinoma. The most common adverse events are fatigue, hand-foot skin reaction, skin rash/desquamation, diarrhea, and hypertension, whereas liver dysfunction is uncommon. To our knowledge, this is the first patient reported in the literature with hepatocellular carcinoma related to nonalcoholic steatohepatitis who died of rapid worsening of liver function during sorafenib treatment. PMID:25702656

  15. Histopathology of hepatocellular carcinoma

    PubMed Central

    Schlageter, Manuel; Terracciano, Luigi Maria; D’Angelo, Salvatore; Sorrentino, Paolo

    2014-01-01

    Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas. PMID:25473149

  16. Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE): study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC) staging system intermediate stage). Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE) is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (90Y-RE) involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE). In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma. Methods/design In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage) hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case of bilobar disease

  17. Concurrent Cisplatin and Radiation Versus Cetuximab and Radiation for Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Koutcher, Lawrence; Sherman, Eric; Fury, Matthew; Wolden, Suzanne; Zhang Zhigang; Mo Qianxing; Stewart, Laschelle; Schupak, Karen; Gelblum, Daphna; Wong, Richard; Kraus, Dennis; Shah, Jatin; Zelefsky, Michael; Pfister, David; Lee, Nancy

    2011-11-15

    Purpose: To compare concurrent cisplatin (CDDP) and radiation (RT) with cetuximab (C225) and RT for locally advanced head-and-neck cancer (LAHNC). Methods and Materials: This study retrospectively compared 174 consecutive, newly diagnosed LAHNC patients definitively treated from March 1, 2006, to April 1, 2008, with single-agent CDDP/RT (n = 125) or C225/RT (n = 49). We excluded patients who received additional concurrent, induction, or adjuvant systemic therapy; weekly cisplatin; prior head-and-neck radiotherapy; or primary surgical resection. Outcomes were analyzed by the Kaplan-Meier method, Cox model, and competing-risks analysis tools. Results: The C225/RT patients were older and had decreased creatinine clearance. At a median follow-up of 22.5 months for living patients, the 2-year locoregional failure rate was 5.7% for CDDP/RT and 39.9% for C225/RT (p < 0.0001). The 2-year failure-free survival (FFS) and overall survival (OS) rates were 87.4% vs. 44.5% (p < 0.0001) and 92.8% vs. 66.6% (p = 0.0003), respectively, in favor of CDDP/RT. When the Cox proportional hazards model was used for multivariate analysis, treatment with CDDP/RT predicted for improved locoregional control (p < 0.0001), FFS (p < 0.0001), and OS (p = 0.01). Late Grade 3 or 4 toxicity or feeding tube dependence 9 months after completion of RT was observed in 21% of patients in the CDDP/RT cohort and 24% in the C225/RT cohort (p = 0.66). Conclusions: In this study of LAHNC patients, CDDP/RT achieved better locoregional control, FFS, and OS than C225/RT. Although the results were upheld on multivariate analysis, they must be interpreted cautiously because of the retrospective nature of the study and significant differences in patient selection. There was no statistically significant difference in late Grade 3 or 4 effects or feeding tube dependence.

  18. PET/CT with Fluorodeoxyglucose During Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

    PubMed Central

    Travaini, Laura L; Zampino, Maria G; Colandrea, Marzia; Ferrari, Mahila E; Gilardi, Laura; Leonardi, Maria C; Santoro, Luigi; Orecchia, Roberto; Grana, Chiara M

    2016-01-01

    Objective The aim of the present study is to evaluate the accuracy of Positron Emission Tomography/Computed Tomography (PET/CT) with Fluorodeoxyglucose ([18F]FDG) to predict treatment response in patients with locally advanced rectal cancer (LARC) during neoadjuvant chemoradiotherapy. Patients and methods Forty-one LARC patients performed [18F]FDG-PET/CT at baseline (PET0). All patients received continuous capecitabine concomitant to radiotherapy on the pelvis, followed by intermittent capecitabine until two weeks before curative surgery. [18F]FDG-PET/CT was also carried out at 40 Gy-time (PET1) and at the end of neoadjuvant therapy (PET2). PET imaging was analysed semi-quantitatively through the measurement of maximal standardised uptake value (SUVmax) and the tumour volume (TV). Histology was expressed through pTNM and Dworak tumor regression grading. Patients were categorised into responder (downstaging or downsizing) and non-responder (stable or progressive disease by comparison pretreatment parameters with clinical/pathological characteristics posttreatment/after surgery). Logistic regression was used to evaluate SUVmax and TV absolute and percent reduction as predictors of response rate using gender, age, and CEA as covariates. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method. Survivals were compared by the Log-Rank test. Results Twenty-three responders (9 ypCR, 14 with downstaged disease) and 18 non-responders showed differences in terms of both early and posttreatment SUVmax percent reduction (median comparison: responder = 63.2%, non-responder = 44.2%, p = 0.04 and responder = 76.9%, non-responder = 61.6%, p = 0.06 respectively). The best predictive cut-offs of treatment response for early and posttreatment SUVmax percent reduction were ≥57% and ≥66% from baseline (p = 0.02 and p = 0.01 respectively). Conclusions [18F]FDG-PET/CT is a reliable technique for evaluating therapy response during neoadjuvant

  19. Sorafenib Tosylate in Treating Patients With Liver Cancer That Cannot Be Removed by Surgery

    ClinicalTrials.gov

    2016-03-01

    Advanced Adult Hepatocellular Carcinoma; Localized Non-Resectable Adult Hepatocellular Carcinoma; Stage III Childhood Hepatocellular Carcinoma; Stage IIIA Hepatocellular Carcinoma; Stage IIIB Hepatocellular Carcinoma; Stage IIIC Hepatocellular Carcinoma; Stage IV Childhood Hepatocellular Carcinoma; Stage IVA Hepatocellular Carcinoma; Stage IVB Hepatocellular Carcinoma

  20. Cost-effectiveness analysis comparing degarelix with leuprolide in hormonal therapy for patients with locally advanced prostate cancer.

    PubMed

    Hatoum, Hind T; Crawford, E David; Nielsen, Sandy Kildegaard; Lin, Swu-Jane; Marshall, Dennis C

    2013-04-01

    Degarelix, approved in the USA in 2008, is a gonadotropin-releasing hormone antagonist, representing one of the latest additions to androgen deprivation therapy (ADT). ADT is used as first-line therapy for locally advanced or metastatic prostate cancer with the aim to reduce testosterone to castrate levels. Like other gonadotropin-releasing hormone-antagonists, degarelix treatment results in rapid decrease in luteinizing hormone, follicle-stimulating hormone and testosterone levels without the associated risk of flare. Using one registration trial for degarelix with leuprolide as the active control, a cost-effectiveness analysis with a Markov model and a 20-year time horizon found the incremental cost-effectiveness ratio for degarelix to be US$245/quality-adjusted life years. Degarelix provides a cost-effective treatment for ADT among patients with locally advanced prostate cancer. PMID:23570437

  1. EGFR monoclonal antibodies in locally advanced head and neck squamous cell carcinoma: What is their current role?

    PubMed

    Alorabi, Mohamed; Shonka, Nicole A; Ganti, Apar Kishor

    2016-03-01

    Treatment options for locally advanced squamous cell carcinoma of the head and neck (SCCHN) include either surgical resection followed by radiation or chemoradiation, or definitive chemoradiation for which single-agent cisplatin is the best studied and established. The increasing understanding of the molecular biology of SCCHN has led to an interest in the development of targeted therapies. The epidermal growth factor receptor (EGFR) is over-expressed in nearly 80-90% of cases of SCCHN and correlates with poor prognosis and resistance to radiation. Preclinical evidence showed that blocking EGFR restores radiation sensitivity and enhances cytotoxicity. This finding led to clinical trials evaluating this class of agents and the approval of cetuximab in combination with radiation for the treatment of locally advanced SCCHN. This review is focused on the anti-EGFR monoclonal antibodies and their role either with radiotherapy or chemoradiation in unresectable LA SCCHN. PMID:26797287

  2. Timing of Therapies in the Multidisciplinary Treatment of Locally Advanced Rectal Cancer: Available Evidence and Implications for Routine Practice.

    PubMed

    Sclafani, Francesco; Chau, Ian

    2016-07-01

    A multimodality disciplinary approach is paramount for the management of locally advanced rectal cancer. Over the last decade, (chemo)radiotherapy followed by surgery plus or minus adjuvant chemotherapy has represented the mainstay of treatment for this disease. Nevertheless, robust evidence suggesting the optimal timing and sequence of therapies in this setting has been overall limited. A number of questions are still unsolved including the length of the interval between neoadjuvant radiotherapy and surgery or the timing of systemic chemotherapy. Interestingly, emerging data support the contention that altering sequence or timing or both of the components of this multimodality approach may provide an opportunity to implement treatment strategies that far better address the risk and expectations of individual patients. In this article, we review the available evidence on timing of therapies in the multidisciplinary treatment of locally advanced rectal cancer and discuss the potential implications for routine practice that may derive from a change of the currently accepted treatment paradigm. PMID:27238468

  3. [Effectiveness of systemic chemotherapy of GEM+CBDCA+5-FU/LV and hepatic arterial infusion of CDDP in a case of advanced, combined hepatocellular-cholangiocarcinoma with multiple lung metastases].

    PubMed

    Tani, Satoshi; Murata, Shigemasa; Tamura, Miho; Fukunaga, Kaoru; Morita, Munetaka; Hirata, Yuzo; Iida, Hiroya; Kakuno, Ayako; Nishigami, Takashi; Yamanaka, Naoki

    2011-11-01

    This patient is a male in his 30's. He was diagnosed as hepatitis B virus-related huge primary liver cancer, 10cm in diameter, located in segment 4, accompanied with left portal thrombus and multiple lung metastases. Ten months after repeating systemic chemotherapy using gemcitabine (GEM)+carboplatin (CBDCA)+5-FU/leucovorin (LV) and hepatic arterial infusion chemotherapy with cisplatin (CDDP) 4 times, extended left lobectomy with caudate lobe could be successfully performed because of marked reducion of the huge tumor. The pathology revealed almost entirely necrotic changes of the main tumor, and the remaining, viable tumor nests showed combined hepatocellular and cholangiocarcinoma. Systemic chemotherapy was repeatedly given afterwards, which kept the pulmonary metastases stable without growth. The present case suggests that systemic chemotherapy using GEM+CBDCA+5-FU/LV may be useful in the multimodal treatment for the combined hepatocellular and cholangiocarcinoma with distant metastases. PMID:22056711

  4. Phase II Trial of Goserelin and Exemestane Combination Therapy in Premenopausal Women With Locally Advanced or Metastatic Breast Cancer

    PubMed Central

    Wang, Jiayu; Xu, Binghe; Yuan, Peng; Ma, Fei; Li, Qing; Zhang, Pin; Cai, Ruigang; Fan, Ying; Luo, Yang; Li, Qiao

    2015-01-01

    Abstract A promising option as the treatment of choice for premenopausal patients with locally advanced or metastatic breast cancer (MBC) could be the combination of a luteinizing hormone-releasing hormone analog and an aromatase inhibitor. However, no prospective studies on the efficacy of goserelin with exemestane in locally advanced or MBC premenopausal breast cancer patients have been reported. We present the phase II trial of goserelin plus exemestane in a total of 44 premenopausal women with locally advanced or MBC. All patients received a subcutaneous injection of 3.6 mg goserelin every 4 weeks along with 25 mg exemestane daily. The primary end point was progression-free survival (PFS). The second end point included overall survival (OS), objective response rate (ORR), duration of response (DOR), and clinical benefit rate (CBR) based on complete response (CR), partial response (PR), or stable disease (SD) for ≥6 months. The median PFS was 13 months (range: 2–42 months). The median DOR was 8 months (range: 2–40 months). Two patients achieved CR (4.5%), and 15 patients experienced PR (34.1%). Fifteen patients (34.1%) had SD ≥6 months. The ORR was 38.6%, and the CBR was 65.9%. Primary progressive disease occurred in 15 patients (34.1%). Five patients (11.4%) died during the study period. Because a few patients have died, the median OS has not been reached. Drug therapy was well tolerated. The most frequent grade-3 adverse events were arthralgia (18.2%), skin rash (6.8%), and myalgia (4.5%). No participants withdrew from the study due to drug toxicity. This study suggested that goserelin and exemestane might be highly effective and well-tolerated regimens in premenopausal women with hormone-responsive, locally advanced or MBC. PMID:26131799

  5. Charged Particle Therapy for Hepatocellular Carcinoma

    PubMed Central

    Skinner, Heath D.; Hong, Theodore S.; Krishnan, Sunil

    2011-01-01

    Historically, the use of external beam radiotherapy for hepatocellular carcinoma (HCC) has been limited by toxicity to the uninvolved liver and surrounding structures. Advances in photon radiotherapy have improved dose conformality to the tumor and facilitated dose escalation, a key contributor to improved HCC radiation treatment outcomes. However, despite these advances in photon radiotherapy, significant volumes of liver still receive low doses of radiation that can preclude dose escalation, particularly in patients with limited functional liver reserves. By capitalizing on the lack of exit dose along the beam path beyond the tumor and higher biological effectiveness, charged particle therapy offers the promise of maximizing tumor control via dose escalation without excessive liver toxicity. In this review we discuss the distinctive biophysical attributes of both proton and carbon ion radiotherapy, particularly as they pertain to treatment of HCC. We also review the available literature regarding clinical outcomes and toxicity of using charged particles for the treatment of HCC. PMID:21939857

  6. Microvascular invasion in hepatocellular carcinoma

    PubMed Central

    Ünal, Emre; İdilman, İlkay Sedakat; Akata, Deniz; Özmen, Mustafa Nasuh; Karçaaltıncaba, Muşturay

    2016-01-01

    Microvascular invasion is a crucial histopathologic prognostic factor for hepatocellular carcinoma. We reviewed the literature and aimed to draw attention to clinicopathologic and imaging findings that may predict the presence of microvascular invasion in hepatocellular carcinoma. Imaging findings suggesting microvascular invasion are disruption of capsule, irregular tumor margin, peritumoral enhancement, multifocal tumor, increased tumor size, and increased glucose metabolism on positron emission tomography-computed tomography. In the presence of typical findings, microvascular invasion may be predicted. PMID:26782155

  7. [The role of regional intra-arterial chemotherapy in the combined treatment of locally advanced laryngeal cancer].

    PubMed

    Mashkova, T A; Ol'shanskiĭ, M S; Panchenko, I G; Ovsiannikov, Iu M; Mal'tsev, A B

    2013-01-01

    The objective of the present study was to estimate the possibilities and prospects for the use of regional intra-arterial chemotherapy in the combined treatment of locally advanced laryngeal cancer. The results of the chemoradiotherapeutic treatment of 26 patients presenting with locally advanced laryngeal cancer were analysed. The chemical agents were selectively administered intra-arterially three times from the right-hand femoral access by the standard procedure at a total focal dose (TFD) of 26 and 50 gram prior to the onset of and during of radiotherapy. The very first administration of the chemical agent resulted in the 30% decrease the tumour size. It further decreased by 70% on the average after the TFD of 50 gram was achieved. It made possible the continuation of gamma-therapy up to the total therapeutic dose. As a result, complete regression of the tumour was documented. The dynamic endoscopic control study and CT of the larynx revealed recurrent laryngeal cancer in 1 of the 26 patients (3.8%). The remaining patients did not develop metastases during the 18 month follow-up period. It is concluded that the results of the present study confirm high (96.2%) effectiveness of the method employed in this study which allows it to be recommended for the organ-preserving treatment of locally advanced laryngeal cancer. PMID:24300761

  8. Volume and dosimetric variations during two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal carcinoma.

    PubMed

    Wang, Rui-hao; Zhang, Shu-xu; Zhou, Ling-hong; Zhang, Guo-qian; Yu, Hui; Lin, Xiao-dan; Lin, Shengqu

    2014-01-01

    The aims of this study were to evaluate the volume and dosimetric variations during IMRT for locally advanced NPC and to identify the benefits of a two-phase adaptive IMRT method. Twenty patients with locally advanced NPC having received IMRT treatment were included. Each patient had both an initial planning CT (CT-1) and a repeated CT scan (CT-2) after treatment at a dose of 40 Gy. Three IMRT planning scenarios were compared: (1) the initial plan on the CT-1 (plan-1); (2) the hybrid plan recalculated the initial plan on the CT-2 (plan-2); (3) the replan generated on the CT-2 being used to complete the course of IMRT (plan-3). The mean gross target volume and mean volumes of the positive neck lymph nodes, high-risk clinical target volume, and the left and right parotid glands significantly decreased by 30.2%, 45.1%, 21.1%, 14.7% and 18.2%, respectively on the CT-2. Comparing plan-2 with plan-1, the dose coverage of the targets remained unchanged, whereas the dose delivered to the parotid glands and spinal cord increased significantly. These patients with locally advanced NPC might benefit from replanning because of the sparing of the parotid glands and spinal cord. PMID:24212016

  9. Phase I study of oral S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer

    SciTech Connect

    Sudo, Kentaro; Yamaguchi, Taketo . E-mail: yama.take@faculty.chiba-u.jp; Ishihara, Takeshi; Nakamura, Kazuyoshi; Shirai, Yoshihiko; Nakagawa, Akihiko; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Saisho, Hiromitsu

    2007-01-01

    Purpose: The primary objective of this study was to determine the maximum-tolerated dose (MTD) of S-1, an oral fluoropyrimidine derivative, with concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day from Day 1 to 14 and 22 to 35 at escalating doses from 60 to 80 mg/m{sup 2}/day. Results: Sixteen patients were enrolled in this study. Three patients received S-1 at 60 mg/m{sup 2}/day, 3 at 70 mg/m{sup 2}/day, and 10 at 80 mg/m{sup 2}/day. Though 1 patient at the final dose level (80 mg/m{sup 2}/day) experienced a dose limiting toxicity (biliary infection with Grade 3 neutropenia), the MTD was not reached in this study. The most common toxicities were anorexia and leukocytopenia, with Grade 3 toxicity occurring in 31% and 6.3% of the patients, respectively. Conclusions: The recommended dose of S-1 with concurrent radiotherapy was determined to be 80 mg/m{sup 2}/day from Day 1 to 14 and 22 to 35 in patients with locally advanced pancreatic cancer. Oral S-1 and radiotherapy is well tolerated and feasible and should be further investigated.

  10. miR-612 suppresses the invasive-metastatic cascade in hepatocellular carcinoma

    PubMed Central

    Tao, Zhong-Hua; Wan, Jin-Liang; Zeng, Ling-Yao; Xie, Lu; Sun, Hui-Chuan; Qin, Lun-Xiu; Wang, Lu; Zhou, Jian; Ren, Zheng-Gang; Li, Yi-Xue

    2013-01-01

    MicroRNAs (miRNAs) play a critical role in tumor metastasis. In this study, we identified a set of 32 miRNAs involved in hepatocellular carcinoma (HCC) metastasis. Among them, miR-612 was shown for the first time to have inhibitory effects on HCC proliferation, migration, invasion, and metastasis. AKT2 was verified to be one of the direct targets of miR-612, through which the epithelial–mesenchymal transition (EMT) and metastasis were inhibited. The level of miR-612 in HCC patients was inversely associated with tumor size, stage, EMT, and metastasis. Of particular importance, miR-612 is involved in both the initial and final steps of the metastatic cascade, by suppressing local invasion and distant colonization. The pleiotropic roles of miR-612 in the HCC metastatic cascade suggest that it could be an effective target for both early and advanced HCC. PMID:23478189

  11. Chemoembolic Hepatopulmonary Shunt Reduction to Allow Safe Yttrium-90 Radioembolization Lobectomy of Hepatocellular Carcinoma

    SciTech Connect

    Gaba, Ron C.; VanMiddlesworth, Kyle A.

    2012-12-15

    Yttrium-90 ({sup 90}Y) radioembolization represents an emerging transcatheter treatment option for the management of hepatocellular carcinoma (HCC). Elevation of the hepatopulmonary shunt fraction risks nontarget radiation to the lungs and may limit the use of {sup 90}Y therapy in patients with locally advanced disease with vascular invasion, who often demonstrate increased shunting. We present two cases in which patients with HCC and portal vein invasion resulting in elevated hepatopulmonary shunt fractions underwent chemoembolic shunt closure to allow safe {sup 90}Y radioembolization. Both patients demonstrated excellent tumor response and patient survival. On this basis, we propose a role for chemoembolic reduction of the lung shunt fraction before {sup 90}Y radioembolization in patients with extensive tumor-related hepatopulmonary shunting.

  12. Hepatocellular Carcinoma (HCC)

    NASA Astrophysics Data System (ADS)

    Helmberger, Thomas K.

    Hepatocellular carcinoma (HCC) is considered to be one of the most common malignancies worldwide, and the most common one in Africa and Asia. Over the last decade, a rising incidence of up to 10-15/100,000 per population has been seen in the Western world, with an estimate of 250,000 deaths and more than a million worldwide per year. By the year 2010, the World Health Organization expects that HCC will be the leading cause of cancer mortality surpassing lung cancer. This increasing incidence is most likely related to an increasing prevalence of chronic hepatitis C (HC) and B (HB) virus infections and other diseases inducing chronic inflammation (Befeler and Di Bisceglie 2002; Llovet et al. 2003).

  13. Diagnosis of hepatocellular carcinoma

    PubMed Central

    Di Bisceglie, Adrian M.

    2005-01-01

    Hepatocellular carcinoma (HCC) is responsible for a large proportion of cancer deaths worldwide. HCC is frequently diagnosed after the development of clinical deterioration at which time survival is measured in months. Long-term survival requires detection of small tumors, often present in asymptomatic individuals, which may be more amenable to invasive therapeutic options. Surveillance of high-risk individuals for HCC is commonly performed using the serum marker alfa-fetoprotein (AFP) often in combination with ultrasonography. Various other serologic markers are currently being tested to help improve surveillance accuracy. Diagnosis of HCC often requires more sophisticated imaging modalities such as CT scan and MRI, which have multiphasic contrast enhancement capabilities. Serum AFP used alone can be helpful if levels are markedly elevated, which occurs in fewer than half of cases at time of diagnosis. Confirmation by liver biopsy can be performed under circumstances when the diagnosis of HCC remains unclear. PMID:18333158

  14. Race and Survival Following Brachytherapy-Based Treatment for Men With Localized or Locally Advanced Adenocarcinoma of the Prostate

    SciTech Connect

    Winkfield, Karen M.; Chen Minghui; Dosoretz, Daniel E.; Salenius, Sharon A.; Katin, Michael; Ross, Rudi; D'Amico, Anthony V.

    2011-11-15

    Purpose: We investigated whether race was associated with risk of death following brachytherapy-based treatment for localized prostate cancer, adjusting for age, cardiovascular comorbidity, treatment, and established prostate cancer prognostic factors. Methods: The study cohort was composed of 5,360 men with clinical stage T1-3N0M0 prostate cancer who underwent brachytherapy-based treatment at 20 centers within the 21st Century Oncology consortium. Cox regression multivariable analysis was used to evaluate the risk of death in African-American and Hispanic men compared to that in Caucasian men, adjusting for age, pretreatment prostate-specific antigen (PSA) level, Gleason score, clinical T stage, year and type of treatment, median income, and cardiovascular comorbidities. Results: After a median follow-up of 3 years, there were 673 deaths. African-American and Hispanic races were significantly associated with an increased risk of all-cause mortality (ACM) (adjusted hazard ratio, 1.77 and 1.79; 95% confidence intervals, 1.3-2.5 and 1.2-2.7; p < 0.001 and p = 0.005, respectively). Other factors significantly associated with an increased risk of death included age (p < 0.001), Gleason score of 8 to 10 (p = 0.04), year of brachytherapy (p < 0.001), and history of myocardial infarction treated with stent or coronary artery bypass graft (p < 0.001). Conclusions: After adjustment for prostate cancer prognostic factors, age, income level, and revascularized cardiovascular comorbidities, African-American and Hispanic races were associated with higher ACM in men with prostate cancer. Additional causative factors need to be identified.

  15. Intraoperative Radiation Therapy Reduces Local Recurrence Rates in Patients With Microscopically Involved Circumferential Resection Margins After Resection of Locally Advanced Rectal Cancer

    SciTech Connect

    Alberda, Wijnand J.; Verhoef, Cornelis; Nuyttens, Joost J.; Meerten, Esther van; Rothbarth, Joost; Wilt, Johannes H.W. de; Burger, Jacobus W.A.

    2014-04-01

    Purpose: Intraoperative radiation therapy (IORT) is advocated by some for patients with locally advanced rectal cancer (LARC) who have involved or narrow circumferential resection margins (CRM) after rectal surgery. This study evaluates the potentially beneficial effect of IORT on local control. Methods and Materials: All surgically treated patients with LARC treated in a tertiary referral center between 1996 and 2012 were analyzed retrospectively. The outcome in patients treated with IORT with a clear but narrow CRM (≤2 mm) or a microscopically involved CRM was compared with the outcome in patients who were not treated with IORT. Results: A total of 409 patients underwent resection of LARC, and 95 patients (23%) had a CRM ≤ 2 mm. Four patients were excluded from further analysis because of a macroscopically involved resection margin. In 43 patients with clear but narrow CRMs, there was no difference in the cumulative 5-year local recurrence-free survival of patients treated with (n=21) or without (n=22) IORT (70% vs 79%, P=.63). In 48 patients with a microscopically involved CRM, there was a significant difference in the cumulative 5-year local recurrence-free survival in favor of the patients treated with IORT (n=31) compared with patients treated without IORT (n=17) (84 vs 41%, P=.01). Multivariable analysis confirmed that IORT was independently associated with a decreased local recurrence rate (hazard ratio 0.24, 95% confidence interval 0.07-0.86). There was no significant difference in complication rate of patients treated with or without IORT (65% vs 52%, P=.18) Conclusion: The current study suggests that IORT reduces local recurrence rates in patients with LARC with a microscopically involved CRM.

  16. Strategies of dose escalation in the treatment of locally advanced non-small cell lung cancer: image guidance and beyond.

    PubMed

    Chi, Alexander; Nguyen, Nam Phong; Welsh, James S; Tse, William; Monga, Manish; Oduntan, Olusola; Almubarak, Mohammed; Rogers, John; Remick, Scot C; Gius, David

    2014-01-01

    Radiation dose in the setting of chemo-radiation for locally advanced non-small cell lung cancer (NSCLC) has been historically limited by the risk of normal tissue toxicity and this has been hypothesized to correlate with the poor results in regard to local tumor recurrences. Dose escalation, as a means to improve local control, with concurrent chemotherapy has been shown to be feasible with three-dimensional conformal radiotherapy in early phase studies with good clinical outcome. However, the potential superiority of moderate dose escalation to 74 Gy has not been shown in phase III randomized studies. In this review, the limitations in target volume definition in previous studies; and the factors that may be critical to safe dose escalation in the treatment of locally advanced NSCLC, such as respiratory motion management, image guidance, intensity modulation, FDG-positron emission tomography incorporation in the treatment planning process, and adaptive radiotherapy, are discussed. These factors, along with novel treatment approaches that have emerged in recent years, are proposed to warrant further investigation in future trials in a more comprehensive and integrated fashion. PMID:24999451

  17. Treatment of locally advanced, high-grade, malignant tumors of major salivary glands

    SciTech Connect

    Reddy, S.P.; Marks, J.E.

    1988-04-01

    A retrospective review of 45 patients with Stage III and IV malignant tumors of the major salivary glands was undertaken to determine tumor control and patient survival after treatment with surgery and conventional ionizing-radiation therapy. Eight of the 23 patients received early postoperative radiotherapy after initial surgical resection, with a local control rate of 75%. Twelve of 23 patients had surgery as definitive treatment and the tumor recurred locally in all; seven of these 12 patients were subsequently salvaged by further surgery plus postoperative radiotherapy or by radiotherapy alone, with 58% ultimate local control. The remaining three patients had unresectable tumors at diagnosis and received radiation alone, with a local tumor control rate of 33%. Patients were also analyzed according to the extent of surgical resection prior to radiation therapy and according to radiation dose. Eighty-eight percent of completely resected, 50% of partially resected, and 44% of unresected tumors were locally controlled for an overall local control rate of 61%. The 5-year survival rate was significantly higher for patients with local tumor control than for patients who failed locally (31% vs. 0%).

  18. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    SciTech Connect

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2012-01-15

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTV{sub P}) and involved lymph nodes (GTV{sub LN}) to simulate the localization process in image-guided radiation therapy. Techniques included ''standard'' (direct registration of weekly images to a planning CT), ''seeded'' (manual prealignment of targets to guide standard registration), ''transitive-based'' (alignment of pretreatment and planning CTs through one or more intermediate images), and ''rereferenced'' (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 {+-} 5.4 mm and 5.4 {+-} 3.4 mm for the GTV{sub P} and GTV{sub LN}, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTV{sub P} centroid LE to 4.7 {+-} 3.7 mm (p = 0.011) and 4.3 {+-} 2.5 mm (p < 1 x 10{sup -3}), respectively, but the smallest GTV{sub P} LE of 2.4 {+-} 2.1 mm was provided by rereferenced registration (p < 1 x 10{sup -6}). Standard registration significantly reduced GTV{sub LN} centroid LE to 3.2 {+-} 2.5 mm (p < 1 x 10{sup -3}) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low

  19. Hepatocellular carcinoma: Where are we?

    PubMed Central

    Mazzanti, Roberto; Arena, Umberto; Tassi, Renato

    2016-01-01

    Hepatocellular carcinoma (HCC) is the second cause of death due to malignancy in the world, following lung cancer. The geographic distribution of this disease accompanies its principal risk factors: Chronic hepatitis B virus and hepatitis C virus infection, alcoholism, aflatoxin B1 intoxication, liver cirrhosis, and some genetic attributes. Recently, type II diabetes has been shown to be a risk factor for HCC together with obesity and metabolic syndrome. Although the risk factors are quite well known and it is possible to diagnose HCC when the tumor is less than 1 cm diameter, it remains elusive at the beginning and treatment is often unsuccessful. Liver transplantation is thus far considered the best treatment for HCC as it cures HCC and the underlying liver disease. Using the Milan criteria, overall survival after liver transplantation for HCC is about 70% after 5 years. Many attempts have been made to go beyond the Milan Criteria and according to recent works reasonably good results have been achieved by using a histochemical marker such as cytokeratine 19 and the so-called “up to seven criteria” to divide patients into categories according to their risk of relapse. In addition to liver transplantation other therapies have been proposed such as resection, tumor ablation by different means, embolization and chemotherapy. An important step in the treatment of advanced HCC has been the introduction of sorafenib, the first oral, systemic drug that has provided significant improvement in survival. Treatment of HCC patients must be multidisciplinary and by using the different approaches discussed in this review it is possible to offer prolonged survival and quite good and sometimes even excellent quality of life to many patients. PMID:26929917

  20. Nonalcoholic fatty liver disease and hepatocellular carcinoma.

    PubMed

    Zoller, Heinz; Tilg, Herbert

    2016-08-01

    The fastest growing cause of cancer-related death is hepatocellular carcinoma (HCC), which is at least partly attributable to the rising prevalence of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to malignant transformation into hepatocellular cancer. The estimated annual HCC incidence in the progressive form of NAFLD - non-alcoholic steatohepatitis (NASH) - is about 0.3%. The risk of HCC development is higher in men and increases with age, more advanced fibrosis, progressive obesity, insulin resistance and diabetes mellitus. Studies on the molecular mechanism of HCC development in NAFLD have shown that hepatocarcinogenesis is associated with complex changes at the immunometabolic interface. In line with these clinical risk factors, administration of a choline-deficient high-fat diet to mice over a prolonged period results in spontaneous HCC development in a high percentage of animals. The role of altered insulin signaling in tumorigenesis is further supported by the observation that components of the insulin-signaling cascade are frequently mutated in hepatocellular cancer cells. These changes further enhance insulin-mediated growth and cell division of hepatocytes. Furthermore, studies investigating nuclear factor kappa B (NF-κB) signaling and HCC development allowed dissection of the complex links between inflammation and carcinogenesis. To conclude, NAFLD reflects an important risk factor for HCC, develops also in non-cirrhotic livers and is a prototypic cancer involving inflammatory and metabolic pathways. STRENGTHS/WEAKNESSES AND SUMMARY OF THE TRANSLATIONAL POTENTIAL OF THE MESSAGES IN THE PAPER: The systematic review summarizes findings from unbiased clinical and translational studies on hepatocellular cancer in non-alcoholic fatty liver disease. This provides a concise overview on the epidemiology, risk factors and molecular

  1. Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

    PubMed Central

    Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

    2016-01-01

    Objectives If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m2, d1), and gemcitabine (1,000 mg/m2 d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. Results In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5–7 and 11–15 months, respectively. The extension of surgery did not affect the outcome. Conclusion The

  2. Outcomes of High-Dose-Rate Interstitial Brachytherapy in the Treatment of Locally Advanced Cervical Cancer: Long-term Results

    SciTech Connect

    Pinn-Bingham, Melva; Puthawala, Ajmel A.; Syed, A.M. Nisar; Sharma, Anil; DiSaia, Philip; Berman, Michael; Tewari, Krishnansu S.; Randall-Whitis, Leslie; Mahmood, Usama; Ramsinghani, Nilam; Kuo, Jeffrey; Chen, Wen-Pin; McLaren, Christine E.

    2013-03-01

    Purpose: The purpose of this study was to determine locoregional control (LRC), disease-free survival (DFS), and toxicity of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the treatment of locally advanced cervical cancer. Methods and Materials: Between March 1996 and May 2009, 116 patients with cervical cancer were treated. Of these, 106 (91%) patients had advanced disease (International Federation of Gynecology and Obstetrics stage IIB-IVA). Ten patients had stage IB, 48 had stage II, 51 had stage III, and 7 had stage IVA disease. All patients were treated with a combination of external beam radiation therapy (EBRT) to the pelvis (5040 cGy) and 2 applications of HDR-ISBT to a dose of 3600 cGy to the implanted volume. Sixty-one percent of patients also received interstitial hyperthermia, and 94 (81%) patients received chemotherapy. Results: Clinical LRC was achieved in 99 (85.3%) patients. Three-year DFS rates were 59%, 67%, 71%, and 57% for patients with stage IB, II, III, and IVA disease, respectively. The 5-year DFS and overall survival rates for the entire group were 60% and 44%, respectively. Acute and late toxicities were within acceptable limits. Conclusions: Locally advanced cervical cancer patients for whom intracavitary BT is unsuitable can achieve excellent LRC and OS with a combination of EBRT and HDR-ISBT.

  3. Outcomes of High-Dose-Rate Interstitial Brachytherapy in the Treatment of Locally Advanced Cervical Cancer: Long-term Results

    PubMed Central

    Pinn-Bingham, Melva; Puthawala, Ajmel A.; Syed, A.M. Nisar; Sharma, Anil; DiSaia, Philip; Berman, Michael; Tewari, Krishnansu S.; Randall-Whitis, Leslie; Mahmood, Usama; Ramsinghani, Nilam; Kuo, Jeffrey; Chen, Wen-Pin; McLaren, Christine E.

    2013-01-01

    Purpose The purpose of this study was to determine locoregional control (LRC), disease-free survival (DFS), and toxicity of high-dose-rate interstitial brachytherapy (HDR-ISBT) in the treatment of locally advanced cervical cancer. Methods and Materials Between March 1996 and May 2009, 116 patients with cervical cancer were treated. Of these, 106 (91%) patients had advanced disease (International Federation of Gynecology and Obstetrics stage IIB-IVA). Ten patients had stage IB, 48 had stage II, 51 had stage III, and 7 had stage IVA disease. All patients were treated with a combination of external beam radiation therapy (EBRT) to the pelvis (5040 cGy) and 2 applications of HDR-ISBT to a dose of 3600 cGy to the implanted volume. Sixty-one percent of patients also received interstitial hyperthermia, and 94 (81%) patients received chemotherapy. Results Clinical LRC was achieved in 99 (85.3%) patients. Three-year DFS rates were 59%, 67%, 71%, and 57% for patients with stage IB, II, III, and IVA disease, respectively. The 5-year DFS and overall survival rates for the entire group were 60% and 44%, respectively. Acute and late toxicities were within acceptable limits. Conclusions Locally advanced cervical cancer patients for whom intracavitary BT is unsuitable can achieve excellent LRC and OS with a combination of EBRT and HDR-ISBT. PMID:22763030

  4. The role of surgery in locally advanced carcinoma of cervix after sub-optimal chemoradiation: Indian scenario

    PubMed Central

    Kundargi, Rajshekar S.; Guruprasad, B.; Hanumantappa, Nikesh; Rathod, Praveen Shankar; Devi, Uma K.; Bafna, U. D.

    2013-01-01

    Background: Standard treatment of advanced cervical cancer is concurrent chemoradiation. Radical radiotherapy for carcinoma cervix includes pelvic external beam radiotherapy (EBRT) with the concomitant platinum based chemotherapy followed by intracavitary brachytherapy (ICBT) to boost central disease. Management of patients who are suboptimally treated, especially, after unsuccessful ICBT insertion is not well-defined. This study explores the role of hysterectomy in these patients. Materials and Methods: From January 2006 to December 2011, 38 patients with locally advanced cervical cancer, in whom ICBT insertion was unsuccessful, were analyzed retrospectively. Operable patients with no parametrial involvement underwent hysterectomy and outcomes (recurrence free and overall survival) were noted. Results: The major complications in post operative period were wound infection, paralytic ileus and bladder atony all of which were conservatively managed with no mortality. At median follow-up of 36 months (range 12-60 months) there was no recurrence in patients with stage 1B2 and stage IIA, 25 out of 38 (65.8%) were event free and the overall survival was 71%. Conclusion: Many patients in Indian scenario receive suboptimal therapy in locally advanced cervical cancer. EBRT with chemotherapy followed by type 1 extra-fascial hysterectomy can be a good alternative for these patients. PMID:24455590

  5. Long-Term Progression-Free Survival in a Patient with Locally Advanced, Unresectable Pancreatic Adenocarcinoma

    PubMed Central

    Kahn, Leonel A; Matin, Mahan; Bold, Richard J; Tanaka, Michael I; Monjazeb, Arta M

    2015-01-01

    Pancreatic adenocarcinoma is amongst the most lethal malignancies with dismal five-year survival rates. Surgical excision is the mainstay of therapy and unresectable disease is considered incurable. Herein, we describe a patient with unresectable, advanced stage pancreatic adenocarcinoma with a remarkable clinical course following definitive chemoradiotherapy. PMID:26824007

  6. Surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft

    PubMed Central

    Bellver-Fernández, Ricardo; Martínez-Rodriguez, Ana-María; Gioia-Palavecino, Claudio; Caffesse, Raul-Guillermo

    2016-01-01

    Background A coronally advanced flap with subepithelial connective tissue graft is the gold standard surgical treatment of gingival recessions, since it offers a higher probability of achieving complete root coverage compared with other techniques. However, optimum short- and middle-term clinical results have also been obtained with coronally advanced flaps alone. The aim of the present study was to evaluate the results obtained by the surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft. Material and Methods The reduction of recession height was assessed, together with the gain in gingival attachment apical to the recession, and total reduction of recession, in a comparative study of two techniques. Twenty-two gingival recessions were operated upon: 13 in the control group (coronally advanced flap) and 9 in the test group (coronally advanced flap associated to subepithelial connective tissue graft). Results After 18 months, the mean reduction of recession height was 2.2 ± 0.8 mm in the control group and 2.3 ± 0.7 mm in the test group, with a mean gain in gingival attachment of 1.3 ± 0.9 mm and 2.3 ± 1.3 mm, respectively. In percentage terms, the mean reduction of recession height was 84.6 ± 19.6% in the control group and 81.7 ± 17.8% in the test group, with a mean gain in gingival attachment of 20.5 ± 37.4% and 184.4 ± 135.5%, respectively. Conclusions Significant reduction of gingival recession was achieved with both techniques, though the mean gain in gingival attachment (in mm and as a %) was greater in test group. Key words:Gingival recession, coronally advanced flap, subepthelial connective tissue graft. PMID:26595836

  7. Long-Term Outcomes With Intraoperative Radiotherapy as a Component of Treatment for Locally Advanced or Recurrent Uterine Sarcoma

    SciTech Connect

    Barney, Brandon M.; Petersen, Ivy A.; Dowdy, Sean C.; Bakkum-Gamez, Jamie N.; Haddock, Michael G.

    2012-05-01

    Purpose: To report our institutional experience with intraoperative radiotherapy (IORT) as a component of treatment for women with locally advanced or recurrent uterine sarcoma. Methods and Materials: From 1990 to 2010, 16 women with primary (n = 3) or locoregionally recurrent (n = 13) uterine sarcoma received IORT as a component of combined modality treatment. Tumor histology studies found leiomyosarcoma (n = 9), endometrial stromal sarcoma (n = 4), and carcinosarcoma (n = 3). Surgery consisted of gross total resection in 2 patients, subtotal resection in 6 patients, and resection with close surgical margins in 8 patients. The median IORT dose was 12.5 Gy (range, 10-20 Gy). All patients received perioperative external beam radiotherapy (EBRT; median dose, 50.4 Gy; range, 20-62.5 Gy), and 6 patients also received perioperative systemic therapy. Results: Seven of the 16 patients are alive at a median follow-up of 44 months (range, 11-203 months). The 3-year Kaplan-Meier estimate of local relapse (within the EBRT field) was 7%, and central control (within the IORT field) was 100%. No local failures occurred in any of the 6 patients who underwent subtotal resection. The 3-year freedom from distant relapse was 48%, with failures occurring most frequently in the lungs or mediastinum. Median survival was 18 months, and 3-year Kaplan-Meier estimates of cause-specific and overall survival were 58% and 53%, respectively. Three patients (19%) experienced late Grade 3 toxicity. Conclusions: A combined modality approach with perioperative EBRT, surgery, and IORT for locally advanced or recurrent uterine sarcoma resulted in excellent local disease control with acceptable toxicity, even in patients with positive resection margins. With this approach, some patients were able to experience long-term freedom from recurrence.

  8. Single-Fraction Stereotactic Body Radiation Therapy and Sequential Gemcitabine for the Treatment of Locally Advanced Pancreatic Cancer

    SciTech Connect

    Schellenberg, Devin; Kim, Jeff; Christman-Skieller, Claudia; Chun, Carlene L.; Columbo, Laurie Ann; Ford, James M.; Fisher, George A.; Kunz, Pamela L.; Van Dam, Jacques; Quon, Andrew; Desser, Terry S.; Norton, Jeffrey; Hsu, Annie; Maxim, Peter G.; Xing, Lei; Goodman, Karyn A.; Chang, Daniel T.; Koong, Albert C.

    2011-09-01

    Purpose: This Phase II trial evaluated the toxicity, local control, and overall survival in patients treated with sequential gemcitabine and linear accelerator-based single-fraction stereotactic body radiotherapy (SBRT). Methods and Materials: Twenty patients with locally advanced, nonmetastatic pancreatic adenocarcinoma were enrolled on this prospective single-institution, institutional review board-approved study. Gemcitabine was administered on Days 1, 8, and 15, and SBRT on Day 29. Gemcitabine was restarted on Day 43 and continued for 3-5 cycles. SBRT of 25 Gy in a single fraction was delivered to the internal target volume with a 2- 3-mm margin using a nine-field intensity-modulated radiotherapy technique. Respiratory gating was used to account for breathing motion. Follow-up evaluations occurred at 4-6 weeks, 10-12 weeks, and every 3 months after SBRT. Results: All patients completed SBRT and a median of five cycles of chemotherapy. Follow-up for the 2 remaining alive patients was 25.1 and 36.4 months. No acute Grade 3 or greater nonhematologic toxicity was observed. Late Grade 3 or greater toxicities occurred in 1 patient (5%) and consisted of a duodenal perforation (G4). Three patients (15%) developed ulcers (G2) that were medically managed. Overall, median survival was 11.8 months, with 1-year survival of 50% and 2-year survival of 20%. Using serial computed tomography, the freedom from local progression was 94% at 1 year. Conclusion: Linear accelerator-delivered SBRT with sequential gemcitabine resulted in excellent local control of locally advanced pancreatic cancer. Future studies will address strategies for reducing long-term duodenal toxicity associated with SBRT.

  9. Neoadjuvant Chemotherapy in Locally Advanced and Borderline Resectable Nonsquamous Sinonasal Tumors (Esthesioneuroblastoma and Sinonasal Tumor with Neuroendocrine Differentiation)

    PubMed Central

    Patil, Vijay M.; Joshi, Amit; Noronha, Vanita; Sharma, Vibhor; Zanwar, Saurabh; Dhumal, Sachin; Kane, Shubhada; Pai, Prathamesh; D'Cruz, Anil; Chaturvedi, Pankaj; Bhattacharjee, Atanu; Prabhash, Kumar

    2016-01-01

    Introduction. Sinonasal tumors are chemotherapy responsive which frequently present in advanced stages making NACT a promising option for improving resection and local control in borderline resectable and locally advanced tumours. Here we reviewed the results of 25 such cases treated with NACT. Materials and Methods. Sinonasal tumor patients treated with NACT were selected for this analysis. These patients received NACT with platinum and etoposide for 2 cycles. Patients who responded and were amenable for gross total resection underwent surgical resection and adjuvant CTRT. Those who responded but were not amenable for resection received radical CTRT. Patients who progressed on NACT received either radical CTRT or palliative radiotherapy. Results. The median age of the cohort was 42 years (IQR 37–47 years). Grades 3-4 toxicity with NACT were seen in 19 patients (76%). The response rate to NACT was 80%. Post-NACT surgery was done in 12 (48%) patients and radical chemoradiation in 9 (36%) patients. The 2-year progression free survival and overall survival were 75% and 78.5%, respectively. Conclusion. NACT in sinonasal tumours has a response rate of 80%. The protocol of NACT followed by local treatment is associated with improvement in outcomes as compared to our historical cohort. PMID:26955484

  10. Concomitant cetuximab and radiation therapy: A possible promising strategy for locally advanced inoperable non-melanoma skin carcinomas

    PubMed Central

    DELLA VITTORIA SCARPATI, GIUSEPPINA; PERRI, FRANCESCO; PISCONTI, SALVATORE; COSTA, GIUSEPPE; RICCIARDIELLO, FILIPPO; DEL PRETE, SALVATORE; NAPOLITANO, ALBERTO; CARRATURO, MARCO; MAZZONE, SALVATORE; ADDEO, RAFFAELE

    2016-01-01

    Non-melanoma skin cancers (NMSCs) include a heterogeneous group of malignancies arising from the epidermis, comprising squamous cell carcinoma (SCC), basal cell carcinoma (BCC), Merkel cell carcinoma and more rare entities, including malignant pilomatrixoma and sebaceous gland tumours. The treatment of early disease depends primarily on surgery. In addition, certain patients present with extensive local invasion or metastasis, which renders these tumours surgically unresectable. Improving the outcome of radiotherapy through the use of concurrent systemic therapy has been demonstrated in several locally advanced cancer-treatment paradigms. Recently, agents targeting the human epidermal growth factor receptor (EGFR) have exhibited a consolidated activity in phase II clinical trials and case series reports. Cetuximab is a monoclonal antibody that binds to and completely inhibits the EGFR, which has been revealed to be up-regulated in a variety of SCCs, including NMSCs. The present review aimed to summarize the role of anti-EGFR agents in the predominant types of NMSC, including SCC and BCC, and focuses on the cetuximab-based studies, highlighting the biological rationale of this therapeutic option. In addition, the importance of the association between cetuximab and radiotherapy for locally advanced NMSC is discussed. PMID:27073643

  11. Intraoperative electron beam radiation therapy for recurrent locally advanced rectal or rectosigmoid carcinoma

    SciTech Connect

    Willett, C.G.; Shellito, P.C.; Tepper, J.E.; Eliseo, R.; Convery, K.; Wood, W.C. )

    1991-03-15

    A multimodality approach of moderate-dose to high-dose preoperative radiation therapy, surgical resection, and intraoperative electron beam radiation therapy (IORT) has been used for patients with locally recurrent rectal or rectosigmoid carcinoma. The 5-year actuarial local control and disease-free survival for 30 patients undergoing this treatment program were 26% and 19%, respectively. The most important factor predicting a favorable outcome was complete resection with negative pathologic resection margins. The determinant local control and disease-free survival for 13 patients undergoing complete resection were 62% and 54%, respectively, whereas for 17 patients undergoing partial resection these figures were 18% and 6%, respectively. There did not appear to be a difference in local control or survival based on the original surgical resection (abdominoperineal resection versus low anterior resection). However, the likelihood of obtaining a complete resection after preoperative radiation therapy was higher in patients who had previously undergone a low anterior resection than patients undergoing prior abdominoperineal resection. For the 30 patients undergoing external beam irradiation, resection, and IORT, the most significant toxicities were soft tissue or sacral injury and pelvic neuropathy. Efforts to further improve local control are directed toward the concurrent use of chemotherapy (5-fluorouracil with and without leucovorin) as radiation dose modifiers during external beam irradiation and the use of additional postoperative radiation therapy.

  12. Microwave ablation of hepatocellular carcinoma

    PubMed Central

    Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

    2015-01-01

    Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s’, RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s’, showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

  13. Microwave ablation of hepatocellular carcinoma.

    PubMed

    Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

    2015-11-01

    Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s', RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s', showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

  14. Toxicity and Efficacy of Concurrent Gemcitabine and Radiotherapy for Locally Advanced Pancreatic Cancer.

    PubMed

    Crane, Christopher; Janjan, N; Evans, D; Wolff, R; Ballo, M; Milas, L; Mason, K; Charnsangavej, C; Pisters, P; Lee, J; Lenzi, R; Vauthey, J; Wong, A; Phan, T; Nguyen, Q; Abbruzzese, J

    2001-01-01

    Gemcitabine has been demonstrated to be a potentradiosensitizer in the laboratory and in the clinic (1-7)and has proven clinical systemic activity to pancreaticcancer. Responses to systemic gemcitabine inpatients with metastatic pancreatic adenocarcinomahave been documented in phase I, phase II, and phaseIII clinical settings (8,9). Moreover, a recent randomizedtrial of gemcitabine vs 5-FU as first-linetherapy in patients with advanced pancreatic adenocarcinomademonstrated a modest median survivalbenefit (4.41 vs 5.65 mo,p= 0.0025) for those patientswho received gemcitabine compared to those whoreceived 5-FU (10). In addition, gemcitabine wasshown to improve cancer-related symptoms and performancestatus as assessed by a quantitative clinicalbenefit scale in both untreated and previouslytreated patients with metastatic adenocarcinoma ofthe pancreas (10,11). Based on these data, the FDAapproved gemcitabine as a first-line agent for patientswith advanced adenocarcinoma of the pancreas. PMID:12754400

  15. A dosimetric comparison of two-phase adaptive intensity-modulated radiotherapy for locally advanced nasopharyngeal cancer.

    PubMed

    Chitapanarux, Imjai; Chomprasert, Kittisak; Nobnaop, Wannapa; Wanwilairat, Somsak; Tharavichitkul, Ekasit; Jakrabhandu, Somvilai; Onchan, Wimrak; Traisathit, Patrinee; Van Gestel, Dirk

    2015-05-01

    The purpose of this investigation was to evaluate the potential dosimetric benefits of a two-phase adaptive intensity-modulated radiotherapy (IMRT) protocol for patients with locally advanced nasopharyngeal cancer (NPC). A total of 17 patients with locally advanced NPC treated with IMRT had a second computed tomography (CT) scan after 17 fractions in order to apply and continue the treatment with an adapted plan after 20 fractions. To simulate the situation without adaptation, a hybrid plan was generated by applying the optimization parameters of the original treatment plan to the anatomy of the second CT scan. The dose-volume histograms (DVHs) and dose statistics of the hybrid plan and the adapted plan were compared. The mean volume of the ipsilateral and contralateral parotid gland decreased by 6.1 cm(3) (30.5%) and 5.4 cm(3) (24.3%), respectively. Compared with the hybrid plan, the adapted plan provided a higher dose to the target volumes with better homogeneity, and a lower dose to the organs at risk (OARs). The Dmin of all planning target volumes (PTVs) increased. The Dmax of the spinal cord and brainstem were lower in 94% of the patients (1.6-5.9 Gy, P < 0.001 and 2.1-9.9 Gy, P < 0.001, respectively). The Dmean of the contralateral parotid decreased in 70% of the patients (range, 0.2-4.4 Gy). We could not find a relationship between dose variability and weight loss. Our two-phase adaptive IMRT protocol improves dosimetric results in terms of target volumes and OARs in patients with locally advanced NPC. PMID:25666189

  16. Surgical treatment for locally advanced lower third rectal cancer after neoadjuvent chemoradiation with capecitabine: prospective phase II trial

    PubMed Central

    Elwanis, Mostafa Abd; Maximous, Doaa W; Elsayed, Mohamed Ibrahim; Mikhail, Nabiel NH

    2009-01-01

    Introduction Treatment of rectal cancer requires a multidisciplinary approach with standardized surgical, pathological and radiotherapeutic procedures. Sphincter preserving surgery for cancer of the lower rectum needs a long-course of neoadjuvant treatments to reduce tumor volume, to induce down-staging that increases circumferential resection margin, and to facilitate surgery. Aim To evaluate the rate of anal sphincter preservation in low lying, resectable, locally advanced rectal cancer and the resectability rate in unresectable cases after neoadjuvent chemoradiation by oral Capecitabine. Patients and methods This trial included 43 patients with low lying (4–7 cm from anal verge) locally advanced rectal cancer, of which 33 were resectable. All patients received preoperative concurrent chemoradiation (45 Gy/25 fractions over 5 weeks with oral capecitabine 825 mg/m2 twice daily on radiotherapy days), followed after 4–6 weeks by total mesorectal excision technique. Results Preoperative chemoradiation resulted in a complete pathologic response in 4 patients (9.3%; 95% CI 3–23.1) and an overall downstaging in 32 patients (74.4%; 95% CI 58.5–85). Sphincter sparing surgical procedures were done in 20 out of 43 patients (46.5%; 95% CI 31.5–62.2). The majority (75%) were of clinical T3 disease. Toxicity was moderate and required no treatment interruption. Grade II anemia occurred in 4 patients (9.3%, 95% CI 3–23.1), leucopenia in 2 patients (4.7%, 95% CI 0.8–17) and radiation dermatitis in 4 patients (9.3%, 95% CI 3–23.1) respectively. Conclusion In patients with low lying, locally advanced rectal cancer, preoperative chemoradiation using oral capecitabine 825 mg/m2, twice a day on radiotherapy days, was tolerable and effective in downstaging and resulted in 46.5% anal sphincter preservation rate. PMID:19508705

  17. Factors Associated With Long-Term Dysphagia After Definitive Radiotherapy for Locally Advanced Head-and-Neck Cancer

    SciTech Connect

    Caudell, Jimmy J.; Schaner, Philip E.; Meredith, Ruby F.; Locher, Julie L.; Nabell, Lisle M.; Carroll, William R.; Magnuson, J. Scott; Spencer, Sharon A.; Bonner, James A.

    2009-02-01

    Purpose: The use of altered fractionation radiotherapy (RT) regimens, as well as concomitant chemotherapy and RT, to intensify therapy for locally advanced head-and-neck cancer can lead to increased rates of long-term dysphagia. Methods and Materials: We identified 122 patients who had undergone definitive RT for locally advanced head-and-neck cancer, after excluding those who had been treated for a second or recurrent head-and-neck primary, had Stage I-II disease, developed locoregional recurrence, had <12 months of follow-up, or had undergone postoperative RT. The patient, tumor, and treatment factors were correlated with a composite of 3 objective endpoints as a surrogate for severe long-term dysphagia: percutaneous endoscopic gastrostomy tube dependence at the last follow-up visit; aspiration on a modified barium swallow study or a clinical diagnosis of aspiration pneumonia; or the presence of a pharyngoesophageal stricture. Results: A composite dysphagia outcome occurred in 38.5% of patients. On univariate analysis, the primary site (p = 0.01), use of concurrent chemotherapy (p = 0.01), RT schedule (p = 0.02), and increasing age (p = 0.04) were significantly associated with development of composite long-term dysphagia. The use of concurrent chemotherapy (p = 0.01), primary site (p = 0.02), and increasing age (p = 0.02) remained significant on multivariate analysis. Conclusion: The addition of concurrent chemotherapy to RT for locally advanced head-and-neck cancer resulted in increased long-term dysphagia. Early intervention using swallowing exercises, avoidance of nothing-by-mouth periods, and the use of intensity-modulated RT to reduce the dose to the uninvolved swallowing structures should be explored further in populations at greater risk of long-term dysphagia.

  18. Pathologic response with neoadjuvant chemotherapy and stereotactic body radiotherapy for borderline resectable and locally-advanced pancreatic cancer

    PubMed Central

    2013-01-01

    Background Neoadjuvant stereotactic body radiotherapy (SBRT) has potential applicability in the management of borderline resectable and locally-advanced pancreatic adenocarcinoma. In this series, we report the pathologic outcomes in the subset of patients who underwent surgery after neoadjuvant SBRT. Methods Patients with borderline resectable or locally-advanced pancreatic adenocarcinoma who were treated with SBRT followed by resection were included. Chemotherapy was to the discretion of the medical oncologist and preceded SBRT for most patients. Results Twelve patients met inclusion criteria. Most (92%) received neoadjuvant chemotherapy, and gemcitabine/capecitabine was most frequently utilized (n = 7). Most were treated with fractionated SBRT to 36 Gy/3 fractions (n = 7) and the remainder with single fraction to 24 Gy (n = 5). No grade 3+ acute toxicities attributable to SBRT were found. Two patients developed post-surgical vascular complications and one died secondary to this. The mean time to surgery after SBRT was 3.3 months. An R0 resection was performed in 92% of patients (n = 11/12). In 25% (n = 3/12) of patients, a complete pathologic response was achieved, and an additional 16.7% (n = 2/12) demonstrated <10% viable tumor cells. Kaplan-Meier estimated median progression free survival is 27.4 months. Overall survival is 92%, 64% and 51% at 1-, 2-, and 3-years. Conclusions This study reports the pathologic response in patients treated with neoadjuvant chemotherapy and SBRT for borderline resectable and locally-advanced pancreatic cancer. In our experience, 92% achieved an R0 resection and 41.7% of patients demonstrated either complete or extensive pathologic response to treatment. The results of a phase II study of this novel approach will be forthcoming. PMID:24175982

  19. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

  20. A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

    SciTech Connect

    Ikeda, Masafumi; Ioka, Tatsuya; Ito, Yoshinori; Yonemoto, Naohiro; Nagase, Michitaka; Yamao, Kenji; Miyakawa, Hiroyuki; Ishii, Hiroshi; Furuse, Junji; Sato, Keiko; Sato, Tosiya; Okusaka, Takuji

    2013-01-01

    Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received a maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.

  1. Phase II Study of Oral S-1 and Concurrent Radiotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

    SciTech Connect

    Sudo, Kentaro; Yamaguchi, Taketo; Ishihara, Takeshi; Nakamura, Kazuyoshi; Hara, Taro; Denda, Tadamichi; Tawada, Katsunobu; Imagumbai, Toshiyuki; Araki, Hitoshi; Sakai, Mitsuhiro; Hatano, Kazuo; Kawakami, Hiroyuki; Uno, Takashi; Ito, Hisao; Yokosuka, Osamu

    2011-05-01

    Purpose: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m{sup 2}/day from day 1 to 14 and 22 to 35. Two weeks after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. Results: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. Conclusions: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.

  2. Use of Respiratory-Correlated Four-Dimensional Computed Tomography to Determine Acceptable Treatment Margins for Locally Advanced Pancreatic Adenocarcinoma

    SciTech Connect

    Goldstein, Seth D.; Ford, Eric C.; Duhon, Mario; McNutt, Todd; Wong, John; Herman, Joseph M.

    2010-02-01

    Purpose: Respiratory-induced excursions of locally advanced pancreatic adenocarcinoma could affect dose delivery. This study quantified tumor motion and evaluated standard treatment margins. Methods and Materials: Respiratory-correlated four-dimensional computed tomography images were obtained on 30 patients with locally advanced pancreatic adenocarcinoma; 15 of whom underwent repeat scanning before cone-down treatment. Treatment planning software was used to contour the gross tumor volume (GTV), bilateral kidneys, and biliary stent. Excursions were calculated according to the centroid of the contoured volumes. Results: The mean +- standard deviation GTV excursion in the superoinferior (SI) direction was 0.55 +- 0.23 cm; an expansion of 1.0 cm adequately accounted for the GTV motion in 97% of locally advanced pancreatic adenocarcinoma patients. Motion GTVs were generated and resulted in a 25% average volume increase compared with the static GTV. Of the 30 patients, 17 had biliary stents. The mean SI stent excursion was 0.84 +- 0.32 cm, significantly greater than the GTV motion. The xiphoid process moved an average of 0.35 +- 0.12 cm, significantly less than the GTV. The mean SI motion of the left and right kidneys was 0.65 +- 0.27 cm and 0.77 +- 0.30 cm, respectively. At repeat scanning, no significant changes were seen in the mean GTV size (p = .8) or excursion (p = .3). Conclusion: These data suggest that an asymmetric expansion of 1.0, 0.7, and 0.6 cm along the respective SI, anteroposterior, and medial-lateral directions is recommended if a respiratory-correlated four-dimensional computed tomography scan is not available to evaluate the tumor motion during treatment planning. Surrogates of tumor motion, such as biliary stents or external markers, should be used with caution.

  3. Hepatocellular carcinoma: natural history, current management, and emerging tools

    PubMed Central

    Tinkle, Christopher L; Haas-Kogan, Daphne

    2012-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver tumor and represents the third-leading cause of cancer-related death in the world. The incidence of HCC continues to increase worldwide, with a unique geographic, age, and sex distribution. The most important risk factor associated with HCC is liver cirrhosis, with the majority of cases caused by chronic infection with hepatitis B (HBV) and C (HCV) viruses and alcohol abuse, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary prevention in the form of HBV vaccination has led to a significant decrease in HBV-related HCC, and initiation of antiviral therapy appears to reduce the incidence of HCC in patients with chronic HBV or HCV infection. Additionally, the use of ultrasonography enables the early detection of small liver tumors and forms the backbone of recommended surveillance programs for patients at high risk for the development of HCC. Cross-sectional imaging studies, including computed tomography and magnetic resonance imaging, represent further noninvasive techniques that are increasingly employed to diagnose HCC in patients with cirrhosis. The mainstay of potentially curative therapy includes surgery – either resection or liver transplantation. However, most patients are ineligible for surgery, because of either advanced disease or underlying liver dysfunction, and are managed with locoregional and/or systemic therapies. Randomized controlled trials have demonstrated a survival benefit with both local therapies, either ablation or embolization, and systemic therapy in the form of the multikinase inhibitor sorafenib. Despite this, median survival remains poor and recurrence rates significant. Further advances in our understanding of the molecular pathogenesis of HCC hold promise in improving the diagnosis and treatment of this highly lethal cancer. PMID:22904613

  4. Current management of hepatocellular carcinoma: An Eastern perspective

    PubMed Central

    Yim, Hyung Joon; Suh, Sang Jun; Um, Soon Ho

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress. PMID:25852267

  5. Combined androgen deprivation therapy and radiation therapy for locally advanced prostate cancer: a randomised, phase 3 trial

    PubMed Central

    Warde, Padraig; Mason, Malcolm; Ding, Keyue; Kirkbride, Peter; Brundage, Michael; Cowan, Richard; Gospodarowicz, Mary; Sanders, Karen; Kostashuk, Edmund; Swanson, Greg; Barber, Jim; Hiltz, Andrea; Parmar, Mahesh KB; Sathya, Jinka; Anderson, John; Hayter, Charles; Hetherington, John; Sydes, Matthew R; Parulekar, Wendy

    2011-01-01

    Summary Background Whether the addition of radiation therapy (RT) improves overall survival in men with locally advanced prostate cancer managed with androgen deprivation therapy (ADT) is unclear. Our aim was to compare outcomes in such patients with locally advanced prostate cancer. Methods Patients with: locally advanced (T3 or T4) prostate cancer (n=1057); or organ-confined disease (T2) with either a prostate-specific antigen (PSA) concentration more than 40 ng/mL (n=119) or PSA concentration more than 20 ng/mL and a Gleason score of 8 or higher (n=25), were randomly assigned (done centrally with stratification and dynamic minimisation, not masked) to receive lifelong ADT and RT (65–69 Gy to the prostate and seminal vesicles, 45 Gy to the pelvic nodes). The primary endpoint was overall survival. The results presented here are of an interim analysis planned for when two-thirds of the events for the final analysis were recorded. All efficacy analyses were done by intention to treat and were based on data from all patients. This trial is registered at controlledtrials.com as ISRCTN24991896 and Clinicaltrials.gov as NCT00002633. Results Between 1995 and 2005, 1205 patients were randomly assigned (602 in the ADT only group and 603 in the ADT and RT group); median follow-up was 6·0 years (IQR 4·4–8·0). At the time of analysis, a total of 320 patients had died, 175 in the ADT only group and 145 in the ADT and RT group. The addition of RT to ADT improved overall survival at 7 years (74%, 95% CI 70–78 vs 66%, 60–70; hazard ratio [HR] 0·77, 95% CI 0·61–0·98, p=0·033). Both toxicity and health-related quality-of-life results showed a small effect of RT on late gastrointestinal toxicity (rectal bleeding grade >3, three patients (0·5%) in the ADT only group, two (0·3%) in the ADT and RT group; diarrhoea grade >3, four patients (0·7%) vs eight (1·3%); urinary toxicity grade >3, 14 patients (2·3%) in both groups). Interpretation The benefits of combined

  6. Nutrition and Hepatocellular Cancer

    PubMed Central

    Schütte, Kerstin; Schulz, Christian; Malfertheiner, Peter

    2016-01-01

    Background Hepatocellular carcinoma (HCC) significantly contributes to the global burden of cancer. Liver cancer is the third most frequent cause of cancer-related death with HCC representing more than 90% of primary liver cancers. The majority of patients are not only affected by the malignant disease but do also suffer from chronic liver disease. Therefore, several factors impact on the prognosis of patients with HCC, including tumor-related factors, liver function and patient-related factors such as performance status and other comorbidities. The nutritional status is of high significance for the patients' performance status, the tolerance of tumor-targeting therapy and the prognosis of cancer of any type and is specially referenced in HCC. This overview is on current concepts on the role of nutritional factors in hepatocarcinogenesis and the role of nutrition in patients affected by HCC. Summary Nutritional status and composition of diet are relevant factors related to the risk of HCC. They also have an important role concerning the prognosis of patients with HCC. Besides risk factors, several macro- and micronutrient components have been found to be inversely correlated with the risk of HCC. To prevent disease progression to liver cirrhosis or HCC in patients with nonalcoholic steatohepatitis, it is crucial to optimize the metabolic state Key Message and Practical Implication Evidence from well-designed prospective interventional trials with the aim to reduce the HCC incidence or to prolong survival in patients with HCC based on nutritional modification is still to be generated. PMID:27403413

  7. Screening for hepatocellular carcinoma.

    PubMed

    Nguyen, Mindie H; Keeffe, Emmet B

    2002-01-01

    Hepatocellular carcinoma (HCC) is common throughout the world and most often develops as a late complication of chronic viral hepatitis or cirrhosis of any cause. As a result of the high prevalence rate of chronic hepatitis C, the incidence of HCC is rising in the United States, as well as in European and Asian countries. The overall survival rate of HCC is poor, and surgical resection and liver transplantation are the only curative treatment options. Screening for HCC offers the best hope for early detection, eligibility for treatment, and improved survival. Most physicians routinely screen at-risk patients with chronic viral hepatitis and cirrhosis for HCC, despite the lack of official guidelines. The current consensus recommendations are to screen healthy hepatitis B virus carriers with annual or semiannual serum alpha-fetoprotein; carriers with chronic hepatitis or cirrhosis and patients with cirrhosis of any etiology are surveyed with twice yearly serum alpha-fetoprotein and liver ultrasound. This article will review the current recommendations for HCC screening, the rationale that led to these recommendations, and the challenges of cost-effectiveness research in this area. PMID:12394211

  8. Staging of hepatocellular carcinoma.

    PubMed

    Duseja, Ajay

    2014-08-01

    Hepatocellular carcinoma (HCC) is different from other malignancies because the prognosis in HCC is not only dependent upon the tumor stage but also on the liver function impairment due to accompanying cirrhosis liver. Various other staging systems used in HCC include the European systems [French staging system, Barcelona Clinic Liver Cancer (BCLC) staging system and the cancer of the liver Italian program (CLIP)] and Asian systems [Okuda staging system, Japan integrated Staging (JIS), Tokyo score and Chinese University Prognostic Index (CUPI)]. Out of all the staging systems used in HCC, Barcelona Clinic Liver Cancer (BCLC) staging system is probably the best because it takes in to account the tumor status (defined by tumor size and number, presence of vascular invasion and extrahepatic spread), liver function (defined either by the Child-Pugh's class) and general health status of the patient (defined by the ECOG classification and the presence of symptoms). Since most of the extrahepatic spread in HCC occurs to lymph nodes, lungs and bones, the assessment can be done with either PET/CT or a combination of CT (Chest and abdomen) and a bone scan. This article describes the various staging systems used in HCC, guides choosing a staging system particularly in the Indian context and the assessment of extra-hepatic spread in HCC. PMID:25755615

  9. Chemoembolization of hepatocellular carcinoma.

    PubMed

    Lencioni, Riccardo; Petruzzi, Pasquale; Crocetti, Laura

    2013-03-01

    Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and relatively preserved liver function. In a meta-analysis of randomized controlled trials comparing conventional TACE regimens-including the administration of an anticancer-in-oil emulsion followed by embolic agents-versus best supportive care, TACE was shown to improve median survival from 16 to 20 months. Various strategies to improve outcomes for this patient group have become the subject of much ongoing clinical research. The introduction of an embolic drug-eluting bead (DEB) has been shown to substantially improve the pharmacokinetic profile of TACE, providing levels of consistency and repeatability not available with conventional regimens while concomitantly significantly diminishing systemic drug exposure. In randomized trials, DEB-TACE significantly reduced liver toxicity and drug-related adverse events compared with conventional TACE. In this article, technique, indications and contraindications, and clinical outcomes of conventional and DEB-TACE in the management of HCC are reviewed. In addition, scientific background and early clinical experience with the use of combination regimens including TACE and systemically active molecular-targeted agents with antiangiogenic properties are discussed. The combination of DEB-TACE and antiangiogenic therapy represents a potentially powerful approach that is currently undergoing clinical investigation in a phase 3 setting. PMID:24436512

  10. Chemoembolization of Hepatocellular Carcinoma

    PubMed Central

    Lencioni, Riccardo; Petruzzi, Pasquale; Crocetti, Laura

    2013-01-01

    Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and relatively preserved liver function. In a meta-analysis of randomized controlled trials comparing conventional TACE regimens—including the administration of an anticancer-in-oil emulsion followed by embolic agents—versus best supportive care, TACE was shown to improve median survival from 16 to 20 months. Various strategies to improve outcomes for this patient group have become the subject of much ongoing clinical research. The introduction of an embolic drug-eluting bead (DEB) has been shown to substantially improve the pharmacokinetic profile of TACE, providing levels of consistency and repeatability not available with conventional regimens while concomitantly significantly diminishing systemic drug exposure. In randomized trials, DEB-TACE significantly reduced liver toxicity and drug-related adverse events compared with conventional TACE. In this article, technique, indications and contraindications, and clinical outcomes of conventional and DEB-TACE in the management of HCC are reviewed. In addition, scientific background and early clinical experience with the use of combination regimens including TACE and systemically active molecular-targeted agents with antiangiogenic properties are discussed. The combination of DEB-TACE and antiangiogenic therapy represents a potentially powerful approach that is currently undergoing clinical investigation in a phase 3 setting. PMID:24436512

  11. Genetic heterogeneity of hepatocellular carcinoma

    SciTech Connect

    Unsal, H.; Isselbacher, K.J. ); Yakicier, C.; Marcais, C.; Ozturk, M. ); Kew, M. ); Volkmann, M. ); Zentgraf, H. )

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  12. Local markets for global health technologies: lessons learned from advancing 6 new products.

    PubMed

    Matthias, Dipika Mathur; Taylor, Catharine H; Sen, Debjeet; Metzler, Mutsumi

    2014-05-01

    Key components to support local institutional and consumer markets are: supply chain, finance, clinical use, and consumer use. Key lessons learned: (1) Build supply and demand simultaneously. (2) Support a lead organization to drive the introduction process. (3) Plan for scale up from the start. (4) Profitability for the private sector is an absolute. PMID:25275438

  13. Progression of Intravesical Condyloma Acuminata to Locally Advanced Poorly Differentiated Squamous Cell Carcinoma.

    PubMed

    Khambati, A; Bhanji, Y; Oberlin, D T; Yang, X J; Nadler, R B; Perry, K T; Kundu, S D

    2016-07-01

    Condyloma acuminata (CA) is a common sexually transmitted disease caused by Human Papilloma Virus (HPV) infection. CA of the bladder, however, is an exceedingly rare lesion. We present a rare case of poorly differentiated locally invasive squamous cell carcinoma (SCC) arising from recurrent CA of the bladder in an immunocompetent patient and discuss pathophysiology and management of this unusual condition. PMID:27335797

  14. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers

    PubMed Central

    Hadaki, Maher; Harrison, Mark

    2013-01-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore—with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of ‘on target’ effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments

  15. Primary Tumor Necrosis Predicts Distant Control in Locally Advanced Soft-Tissue Sarcomas After Preoperative Concurrent Chemoradiotherapy

    SciTech Connect

    MacDermed, Dhara M.; Miller, Luke L.; Peabody, Terrance D.; Simon, Michael A.; Luu, Hue H.; Haydon, Rex C.; Montag, Anthony G.; Undevia, Samir D.

    2010-03-15

    Purpose: Various neoadjuvant approaches have been evaluated for the treatment of locally advanced soft-tissue sarcomas. This retrospective study describes a uniquely modified version of the Eilber regimen developed at the University of Chicago. Methods and Materials: We treated 34 patients (28 Stage III and 6 Stage IV) with locally advanced soft-tissue sarcomas of an extremity between 1995 and 2008. All patients received preoperative therapy including ifosfamide (2.5 g/m2 per day for 5 days) with concurrent radiation (28 Gy in 3.5-Gy daily fractions), sandwiched between various chemotherapy regimens. Postoperatively, 47% received further adjuvant chemotherapy. Results: Most tumors (94%) were Grade 3, and all were T2b, with a median size of 10.3 cm. Wide excision was performed in 29 patients (85%), and 5 required amputation. Of the resected tumor specimens, 50% exhibited high (>=90%) treatment-induced necrosis and 11.8% had a complete pathologic response. Surgical margins were negative in all patients. The 5-year survival rate was 42.3% for all patients and 45.2% for Stage III patients. For limb-preservation patients, the 5-year local control rate was 89.0% and reoperation was required for wound complications in 17.2%. The 5-year freedom-from-distant metastasis rate was 53.4% (Stage IV patients excluded), and freedom from distant metastasis was superior if treatment-induced tumor necrosis was 90% or greater (84.6% vs. 19.9%, p = 0.02). Conclusions: This well-tolerated concurrent chemoradiotherapy approach yields excellent rates of limb preservation and local control. The resulting treatment-induced necrosis rates are predictive of subsequent metastatic risk, and this information may provide an opportunity to guide postoperative systemic therapies.

  16. The status of targeted agents in the setting of neoadjuvant radiation therapy in locally advanced rectal cancers.

    PubMed

    Glynne-Jones, Rob; Hadaki, Maher; Harrison, Mark

    2013-09-01

    Radiotherapy has a longstanding and well-defined role in the treatment of resectable rectal cancer to reduce the historically high risk of local recurrence. In more advanced borderline or unresectable cases, where the circumferential resection margin (CRM) is breached or threatened according to magnetic resonance imaging (MRI), despite optimized local multimodality treatment and the gains achieved by modern high quality total mesorectal excision (TME), at least half the patients fail to achieve sufficient downstaging with current schedules. Many do not achieve an R0 resection. In less locally advanced cases, even if local control is achieved, this confers only a small impact on distant metastases and a significant proportion of patients (30-40%) still subsequently develop metastatic disease. In fact, distant metastases have now become the predominant cause of failure in rectal cancer. Therefore, increasing the intensity and efficacy of chemotherapy and chemoradiotherapy by integrating additional cytotoxics and biologically targetted agents seems an appealing strategy to explore-with the aim of enhancing curative resection rates and improving distant control and survival. However, to date, we lack validated biomarkers for these biological agents apart from wild-type KRAS. For cetuximab, the appearance of an acneiform rash is associated with response, but low levels of magnesium appear more controversial. There are no molecular biomarkers for bevacizumab. Although some less invasive clinical markers have been proposed for bevacizumab, such as circulating endothelial cells (CECS), circulating levels of VEGF and the development of overt hypertension, these biomarkers have not been validated and are observed to emerge only after a trial of the agent. We also lack a simple method of ongoing monitoring of 'on target' effects of these biological agents, which could determine and pre-empt the development of resistance, prior to radiological and clinical assessessments or

  17. Immunological landscape and immunotherapy of hepatocellular carcinoma.

    PubMed

    Prieto, Jesús; Melero, Ignacio; Sangro, Bruno

    2015-12-01

    Advanced hepatocellular carcinoma (HCC) is a serious therapeutic challenge and targeted therapies only provide a modest benefit in terms of overall survival. Novel approaches are urgently needed for the treatment of this prevalent malignancy. Evidence demonstrating the antigenicity of tumour cells, the discovery that immune checkpoint molecules have an essential role in immune evasion of tumour cells, and the impressive clinical results achieved by blocking these inhibitory receptors, are revolutionizing cancer immunotherapy. Here, we review the data on HCC immunogenicity, the mechanisms for HCC immune subversion and the different immunotherapies that have been tested to treat HCC. Taking into account the multiplicity of hyperadditive immunosuppressive forces acting within the HCC microenvironment, a combinatorial approach is advised. Strategies include combinations of systemic immunomodulation and gene therapy, cell therapy or virotherapy. PMID:26484443

  18. Fibrolamellar hepatocellular carcinoma: current clinical perspectives

    PubMed Central

    Lafaro, Kelly J; Pawlik, Timothy M

    2015-01-01

    Fibrolamellar carcinoma (FLC) is a variant of hepatocellular carcinoma (HCC), which comprises ∼1%–9% of all HCCs. Although FLC is a variant of HCC, it is distinct from HCC in that it most often affects younger patients (10–35 years of age) with no underlying liver disease. FLC often presents with vague abdominal pain, nausea, abdominal fullness, malaise, and weight loss. Surgery is the current mainstay of treatment for FLC and remains the only potentially curative option. While FLCs are considered less responsive to chemotherapy than their classic HCC counterparts, there have been suggestions that multimodality treatments may be effective, especially in advanced cases. Further research is necessary to determine effective systemic therapies as an adjunct to surgery for FLC. PMID:27508204

  19. The mutational landscape of hepatocellular carcinoma

    PubMed Central

    2015-01-01

    The development of hepatocellular carcinoma (HCC) is a complex process, and HCC arises from the accumulation of multiple genetic alterations leading to changes in the genomic landscape. Current advances in genomic technologies have revolutionized the search for genetic alterations in cancer genomes. Recent studies in which all coding exons in HCC were sequenced have shed new light on the genomic landscape of this malignant disease. Catalogues of these somatic mutations and systematic analysis of catalogued mutations will lead us to uncover candidate HCC driver genes, although further functional validation is needed to determine whether these genes play a causal role in the development of HCC. This review provides an overview of previously known oncogenes and new oncogene candidates in HCC that were uncovered from recent exome or whole-genome sequencing studies. This knowledge provides direction for future personalized treatment approaches for patients with HCC. PMID:26523267

  20. Potentiality of immunotherapy against hepatocellular carcinoma

    PubMed Central

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future. PMID:26420958

  1. Hypofractionated Accelerated Radiotherapy With Concurrent Chemotherapy For Locally Advanced Squamous Cell Carcinoma of the Head and Neck

    SciTech Connect

    Sanghera, Paul; McConkey, Chris; Ho, Kean-Fatt; Glaholm, John; Hartley, Andrew . E-mail: andrew.hartley@uhb.nhs.uk

    2007-04-01

    Purpose: To investigate the tumor control rates in locally advanced head-and-neck cancer using accelerated hypofractionated radiotherapy with chemotherapy. Methods and Materials: The data from patients with squamous cell cancer of the larynx, oropharynx, oral cavity, and hypopharynx (International Union Against Cancer Stage II-IV), who received accelerated hypofractionated radiotherapy with chemotherapy between January 1, 1998, and April 1, 2005, were retrospectively analyzed. Two different chemotherapy schedules were used, carboplatin and methotrexate, both single agents administered on an outpatient basis. The endpoints were overall survival, local control, and disease-free survival. Results: A total of 81 patients were analyzed. The 2-year overall survival rate was 71.6% (95% confidence interval [CI], 61.5-81.8%). The 2-year disease-free survival rate was 68.6% (95% CI, 58.4-78.8%). The 2-year local control rate was 75.4% (95% CI, 65.6-85.1%). When excluding patients with Stage II oral cavity, larynx, and hypopharynx tumors, 68 patients remained. For these patients, the 2-year overall survival, local control, and disease-free survival rate was 67.6% (95% CI, 56.0-79.2%), 72.0% (95% CI, 61.0-83.0%), and 64.1% (95% CI, 52.6-75.7%), respectively. Conclusion: Accelerated hypofractionated radiotherapy and synchronous chemotherapy can achieve high tumor control rates while being resource sparing and should be the subject of prospective evaluation.

  2. Treatment experience: locally advanced sarcomas with 15 MeV fast neutrons

    SciTech Connect

    Ornitz, R.; Herskovic, A.; Schell, M.; Fender, F.; Rogers, C.C.

    1980-06-01

    Experience with ten evaluable osseous sarcomas and ten evaluable advanced soft tissue sarcomas treated with neutrons of a mean neutron energy of 15 MeV are described. Neutron irradiation with or without conventional megavoltage radiotherapy is an effective modality in the treatment of these patients. No correlation between response rate and grade or whether fast neutrons alone or combined with megavoltage radiotherapy was noted. Those patients receiving a neutron dose of 2195 neutron plus gamma rads or greater all had a complete response.

  3. Characterization of failure modes in deep UV and deep green LEDs utilizing advanced semiconductor localization techniques.

    SciTech Connect

    Tangyunyong, Paiboon; Miller, Mary A.; Cole, Edward Isaac, Jr.

    2012-03-01

    We present the results of a two-year early career LDRD that focused on defect localization in deep green and deep ultraviolet (UV) light-emitting diodes (LEDs). We describe the laser-based techniques (TIVA/LIVA) used to localize the defects and interpret data acquired. We also describe a defect screening method based on a quick electrical measurement to determine whether defects should be present in the LEDs. We then describe the stress conditions that caused the devices to fail and how the TIVA/LIVA techniques were used to monitor the defect signals as the devices degraded and failed. We also describe the correlation between the initial defects and final degraded or failed state of the devices. Finally we show characterization results of the devices in the failed conditions and present preliminary theories as to why the devices failed for both the InGaN (green) and AlGaN (UV) LEDs.

  4. Local and global principles of striate cortical organization: an advanced model.

    PubMed

    Bauer, R; Dow, B M

    1991-01-01

    A model of the functional architecture in monkey striate cortex is proposed, based on recent data, in which the global structure is a result of the local structure. The local structure itself is organized around the cytochrome oxidase blobs. It is characterized by different anisotropic distributions of preferred orientations in upper and lower layers. In particular, the upper layers show a bias for "radial" orientations and the lower layers show a bias for "concentric" orientations (Bauer and Dow 1989). This organization may derive from the symmetry of the visual field and visual system which tends to be radial or concentric rather than cartesian. Functionally, the increased sensitivities of the different radial and concentric maps of orientation and movement detectors seem to be an adaptive fit to optic flow fields on the retina during complex movements of the subject in its environment. PMID:1650592

  5. Modeling Combined Chemotherapy and Particle Therapy for Locally Advanced Pancreatic Cancer

    PubMed Central

    Durante, Marco; Tommasino, Francesco; Yamada, Shigeru

    2015-01-01

    Pancreatic ductal adenocarcinoma is the only cancer for which deaths are predicted to increase in 2014 and beyond. Combined radiochemotherapy protocols using gemcitabine and hypofractionated X-rays are ongoing in several clinical trials. Recent results indicate that charged particle therapy substantially increases local control of resectable and unresectable pancreas cancer, as predicted from previous radiobiology studies considering the high tumor hypoxia. Combination with chemotherapy improves the overall survival (OS). We compared published data on X-ray and charged particle clinical results with or without adjuvant chemotherapy calculating the biological effective dose. We show that chemoradiotherapy with protons or carbon ions results in 1 year OS significantly higher than those obtained with other treatment schedules. Further hypofractionation using charged particles may result in improved local control and survival. A comparative clinical trial using the standard X-ray scheme vs. the best current standard with carbon ions is crucial and may open new opportunities for this deadly disease. PMID:26217585

  6. Epidermal growth factor receptor as a predictor of tumor downstaging in locally advanced rectal cancer patients treated with preoperative chemoradiotherapy

    SciTech Connect

    Kim, Jun-Sang . E-mail: k423j@cnu.ac.kr; Kim, Jin-Man; Li, Shengjin; Yoon, Wan-Hee; Song, Kyu-Sang; Kim, Ki-Hwan; Yeo, Seung-Gu; Nam, Ji Sook; Cho, Moon-June

    2006-09-01

    Purpose: To examine retrospectively whether levels of epidermal growth factor receptor (EGFR) expression can predict tumor downstaging after preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Methods and Materials: A total of 183 patients with rectal cancer (cT3-T4 or N+) were enrolled in this study. Preoperative chemoradiotherapy consisted of 50.4 Gy of pelvic radiation with concurrent 5-fluorouracil and leucovorin bolus intravenous chemotherapy in 94 patients or oral capecitabine and leucovorin in 89 patients. EGFR expression in pretreatment paraffin-embedded tumor biopsy specimens was assessed by immunohistochemistry. EGFR expression was determined from the intensity and extent of staining. Tumor downstaging was defined as a reduction of at least one T-stage level. Results: Tumor downstaging occurred in 97 patients (53%), and the tumors showed a pathologic complete response in 27 patients (15%). Positive EGFR expression was observed in 140 (76%) of 183 patients. EGFR expression levels were low in 113 patients (62%) and high in 70 patients (38%). On logistic regression analysis, the significant predictive factor for increased tumor downstaging was a low level of EGFR expression and preoperative chemotherapy using oral capecitabine (odds ratio, 0.437; p 0.012 vs. odds ratio, 3.235; p < 0.001, respectively). Conclusion: A high level of EGFR expression may be a significant predictive molecular marker for decreased tumor downstaging after preoperative chemoradiotherapy in locally advanced rectal cancer.

  7. Anatomic and Dosimetric Changes During the Treatment Course of Intensity-Modulated Radiotherapy for Locally Advanced Nasopharyngeal Carcinoma

    SciTech Connect

    Wang Xin; Lu Jiade; Xiong Xiaopeng; Zhu Guopei; Ying Hongmei; He Shaoqin; Hu Weigang; Hu Chaosu

    2010-07-01

    Many patients with nasopharyngeal carcinoma (NPC) have marked anatomic change during intensity-modulated radiation therapy (IMRT). In this study, the magnitude of anatomic changes and its dosimetric effects were quantified. Fifteen patients with locally advanced NPC treated with IMRT had repeated computed tomography (CT) after 18 fractions. A hybrid plan was made to the anatomy of the second computed tomography scan. The dose of the original plan, hybrid plan, and new plan were compared. The mean volume of left and right parotid decreased 6.19 mL and 6.44 mL, respectively. The transverse diameters of the upper bound of odontoid process, the center of odontoid process, and the center of C2 vertebral body slices contracted with the mean contraction of 8.2 mm, 9.4 mm, and 7.6 mm. Comparing the hybrid plan with the treatment plan, the coverage of target was maintained while the maximum dose to the brain stem and spinal cord increased by 0.08 to 6.51 Gy and 0.05 to 7.8 Gy. The mean dose to left and right parotid increased by 2.97 Gy and 2.57 Gy, respectively. A new plan reduced the dose of spinal cord, brain stem, and parotids. Measurable anatomic changes occurring during the IMRT for locally advanced NPC maintained the coverage of targets but increased the dose to critical organs. Those patients might benefit from replanning.

  8. Locally Advanced Rectal Cancer Patients Receiving Radio-Chemotherapy: A Novel Clinical-Pathologic Score Correlates With Global Outcome

    SciTech Connect

    Berardi, Rossana; Mantello, Giovanna; Scartozzi, Mario; Del Prete, Stefano; Luppi, Gabriele; Martinelli, Roberto; Fumagalli, Marco; Grillo-Ruggieri, Filippo; Bearzi, Italo; Mandolesi, Alessandra; Marmorale, Cristina; Cascinu, Stefano

    2009-12-01

    Purpose: To determine the importance of downstaging of locally advanced rectal cancer after neoadjuvant treatment. Methods and Materials: The study included all consecutive patients with locally advanced rectal cancer who underwent neoadjuvant treatment (chemotherapy and/or radiotherapy) in different Italian centers from June 1996 to December 2003. A novel score was used, calculated as the sum of numbers obtained by giving a negative or positive point, respectively, to each degree of increase or decrease in clinical to pathologic T and N status. Results: A total of 317 patients were eligible for analysis. Neoadjuvant treatments performed were as follows: radiotherapy alone in 75 of 317 patients (23.7%), radiotherapy plus chemotherapy in 242 of 317 patients (76.3%). Worse disease-free survival was observed in patients with a lower score (Score 1 = -3 to +3 vs. Score 2 = +4 to +7; p = 0.04). Conclusions: Our results suggest that a novel score, calculated from preoperative and pathologic tumor and lymph node status, could represent an important parameter to predict outcome in patients receiving neoadjuvant treatment for rectal cancer. The score could be useful to select patients for adjuvant chemotherapy after neoadjuvant treatment and surgery.

  9. Treatment of locally advanced pancreatic cancer by percutaneous and intraoperative irreversible electroporation: general hospital cancer center experience.

    PubMed

    Lambert, L; Horejs, J; Krska, Z; Hoskovec, D; Petruzelka, L; Krechler, T; Kriz, P; Briza, J

    2016-01-01

    The aim of this study was to evaluate the safety of irreversible electroporation (IRE) and the outcome of patients undergoing IRE of locally advanced pancreatic cancer (PC). Twenty-one patients with unresectable PC underwent open (n=19) or percutaneous (n=2) IRE of the tumor using the Nanoknife system with two electrodes that were repositioned several times to affect the whole mass. The size of the tumor was 39±10mm with a range from 21 to 65mm. Five patients underwent neoadjuvant chemotherapy and seven patients were treated with chemotherapy after IRE. Complications occurred in five patients, which resulted in prolongation of the average hospital stay from 10 to 34 days. There was no mortality in the first postoperative month. Median survival after IRE was 10.2 months compared to 9.3 months in a matched cohort (hazard ratio = .54, p = .053). The quality of life was declining slowly. 81% of time after IRE the Karnofsky performance status was ≥70 and sharp decline occurred approximately 8 weeks before death.In conclusion, IRE is a safe palliative treatment option for a percentage of patients with locally advanced pancreatic carcinoma. The patients treated with open IRE lived a decent life until 8 weeks before their death. We believe that IRE of pancreatic carcinoma can be regarded as an option, if imaging or explorative laparotomy show that R0 resection in not possible. PMID:26774149

  10. Evaluation of the Dosimetric Feasibility of Hippocampal Sparing Intensity-Modulated Radiotherapy in Patients with Locally Advanced Nasopharyngeal Carcinoma

    PubMed Central

    Gan, Hua; Denniston, Kyle A.; Li, Sicong; Tan, Wenyong; Wang, Zhaohua

    2014-01-01

    Purpose The objective of this study was to evaluate the dosimetric feasibility of using hippocampus (HPC) sparing intensity-modulated radiotherapy (IMRT) in patients with locally advanced nasopharyngeal carcinoma (NPC). Materials/Methods Eight cases of either T3 or T4 NPC were selected for this study. Standard IMRT treatment plans were constructed using the volume and dose constraints for the targets and organs at risk (OAR) per Radiation Therapy Oncology Group (RTOG) 0615 protocol. Experimental plans were constructed using the same criteria, with the addition of the HPC as an OAR. The two dose-volume histograms for each case were compared for the targets and OARs. Results All plans achieved the protocol dose criteria. The homogeneity index, conformity index, and coverage index for the planning target volumes (PTVs) were not significantly compromised by the avoidance of the HPC. The doses to all OARs, excluding the HPC, were similar. Both the dose (Dmax, D2%, D40%, Dmean, Dmedian, D98% and Dmin) and volume (V5, V10, V15, V20, V30, V40 and V50) parameters for the HPC were significantly lower in the HPC sparing plans (p<0.05), except for Dmin (P = 0.06) and V5 (P = 0.12). Conclusions IMRT for patients with locally advanced NPC exposes the HPC to a significant radiation dose. HPC sparing IMRT planning significantly decreases this dose, with minimal impact on the therapeutic targets and other OARs. PMID:24587184

  11. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

    PubMed Central

    Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

    2016-01-01

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma. PMID:27390539

  12. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review.

    PubMed

    Lee, Edward Wolfgang; Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

    2016-01-01

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma. PMID:27390539

  13. Infiltrative Hepatocellular Carcinoma

    PubMed Central

    Yan, Xiaopeng; Fu, Xu; Deng, Min; Chen, Jun; He, Jian; Shi, Jiong; Qiu, Yudong

    2016-01-01

    Abstract Data on infiltrative hepatocellular carcinoma (iHCC) receiving hepatectomy are unclear. Our study assessed the outcomes, effects of anatomical resection, and prognostic factors in a cohort of Chinese patients with iHCC undergoing hepatectomy. Data from 47 patients with iHCC undergoing hepatectomy were analyzed in a retrospective study. Independent prognostic factors of overall survival (OS) and recurrence-free survival (RFS) were identified using univariate and multivariate analyses. Correlations between microvascular invasion (MVI) and clinicopathological features were assessed using the χ2 test, Student t test, or the Mann–Whitney U test. Survival outcomes were estimated using the Kaplan-Meier method. The median OS was 27.37 months and the 1-year RFS rate were 61.7%. Alpha-fetoprotein (AFP) level was not a specific parameter in iHCC patients undergoing hepatectomy. Anatomic resection was significantly associated with increased RFS (P = 0.007). Patients showing MVI were observed with decreased RFS (P < 0.001). A high lactate dehydrogenase (LDH) level was significantly associated with decreased OS and RFS (P = 0.003 and P = 0.020, respectively). MVI was shown correlated with the levels of aspartate aminotransferase (AST), gamma glutamyl transpeptidase (GGT), and LDH. Subgroup analysis indicated that in mild MVI group, survival outcome was significantly more favorable in patients with high LDH level (P = 0.019). iHCC patients are related with higher MVI rate and patients may still derive survival benefit from anatomic resection at early and intermediate stages. MVI classification could be used to identify iHCC patients with a poorer survival, especially those with a high preoperative LDH level. PMID:27175659

  14. Antibiotics/antimicrobials: systemic and local administration in the therapy of mild to moderately advanced periodontitis.

    PubMed

    Jepsen, Karin; Jepsen, Søren

    2016-06-01

    This review gives an update of the current scientific evidence on the efficacy of the adjunctive use of systemic and local antibiotics/antimicrobials in the treatment of periodontitis. In particular, it addresses whether their use can improve the results of nonsurgical mechanical therapy in mild-to-moderate forms of the disease. Large numbers of randomized clinical trials and systematic reviews with meta-analyses have clearly established that adjunctive systemic antibiotics, combined with mechanical debridement, offer clinical improvements additional to those obtained with scaling and root planing alone. These effects are more pronounced in aggressive periodontitis and in initially deep pockets, whereas more limited additional improvements, of 0.3 mm for additional pocket reduction and 0.2 mm for additional clinical attachment gain, have been documented for moderately deep sites (4-6 mm) in patients with chronic periodontitis. The marginal clinical benefit in patients with moderate disease has to be balanced against possible side effects. Notably, it has to be realized that an increasing number of warnings have been articulated against the unrestricted use of antibiotics in treating periodontal diseases because of the emerging global public health issue of bacterial resistance. The effects of the adjunctive local administration of antimicrobials have also been very well documented in several systematic reviews. Overall, in persistent or recurrent localized deep sites, the application of antimicrobials by sustained-delivery devices may offer a benefit of an additional 0.4 mm in pocket depth reduction and 0.3 mm in clinical attachment level gain. In conclusion, the slight additional benefits of adjunctive antimicrobials, which were shown for moderate forms of periodontitis, have to be balanced against their side effects and therefore their prescription should be limited as much as possible. PMID:27045432

  15. Neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer.

    PubMed

    Doi, Hiroshi; Beppu, Naohito; Odawara, Soichi; Tanooka, Masao; Takada, Yasuhiro; Niwa, Yasue; Fujiwara, Masayuki; Kimura, Fumihiko; Yanagi, Hidenori; Yamanaka, Naoki; Kamikonya, Norihiko; Hirota, Shozo

    2013-11-01

    The purpose of this study was to examine the safety and feasibility of a novel protocol of neoadjuvant short-course hyperfractionated accelerated radiotherapy (SC-HART) combined with S-1 for locally advanced rectal cancer. A total of 56 patients with lower rectal cancer of cT3N1M0 (Stage III b) was treated with SC-HART followed by radical surgery, and were analyzed in the present study. SC-HART was performed with a dose of 2.5 Gy twice daily, with an interval of at least 6 hours between fractions, up to a total dose of 25 Gy (25 Gy in 10 fractions for 5 days) combined with S-1 for 10 days. Radical surgery was performed within three weeks following the end of the SC-HART. The median age was 64.6 (range, 39-85) years. The median follow-up term was 16.3 (range, 2-53) months. Of the 56 patients, 53 (94.4%) had no apparent adverse events before surgery; 55 (98.2%) completed the full course of neoadjuvant therapy, while one patient stopped chemotherapy because of Grade 3 gastrointestinal toxicity (CTCAE v.3). The sphincter preservation rate was 94.6%. Downstaging was observed in 45 patients (80.4%). Adjuvant chemotherapy was administered to 43 patients (76.8%). The local control rate, disease-free survival rate and disease-specific survival rate were 100%, 91.1% and 100%, respectively. To conclude, SC-HART combined with S-1 for locally advanced rectal cancer was well tolerated and produced good short-term outcomes. SC-HART therefore appeared to have a good feasibility for use in further clinical trials. PMID:23658415

  16. Clinicopathological evaluation of pre-operative chemoradiotherapy with S-1 as a treatment for locally advanced oral squamous cell carcinoma

    PubMed Central

    KAWANO, SHINTARO; ZHENG, YANQUN; OOBU, KAZUNARI; MATSUBARA, RYOTA; GOTO, YUICHI; CHIKUI, TORU; YOSHITAKE, TADAMASA; KIYOSHIMA, TAMOTSU; JINNO, TEPPEI; MARUSE, YASUYUKI; MITATE, EIJI; KITAMURA, RYOJI; TANAKA, HIDEAKI; TOYOSHIMA, TAKESHI; SUGIURA, TSUYOSHI; NAKAMURA, SEIJI

    2016-01-01

    The administration of pre-operative chemotherapy with S-1 and concurrent radiotherapy at a total dose of 30 Gy was clinicopathologically evaluated as a treatment for locally advanced oral squamous cell carcinoma (OSCC) in the present study. The participants comprised 81 patients with OSCC, consisting of 29 patients with stage II disease, 12 patients with stage III disease and 40 patients with stage IV disease. All patients received a total radiation dose of 30 Gy in daily fractions of 2 Gy, 5 times a week, for 3 weeks, and the patients were concurrently administered S-1 at a dose of 80–120 mg, twice daily, over 4 consecutive weeks. Radical surgery was performed in all cases at 2–6 weeks subsequent to the end of pre-operative chemoradiotherapy. The most common adverse event was oropharyngeal mucositis, but this was transient in all patients. No severe hematological or non-hematological toxicities were observed. The clinical and histopathological response rates were 70.4 and 75.3%, respectively. Post-operatively, local failure developed in 6 patients (7.4%) and neck failure developed in 2 patients (2.5%). Distant metastases were found in 7 patients (8.6%). The overall survival rate, disease-specific survival rate and locoregional control rate at 5 years were 87.7, 89.9 and 90.6%, respectively. Locoregional recurrence occurred more frequently in patients that demonstrated a poor histopathological response compared with patients that demonstrated a good response (P<0.01). These results indicate that pre-operative S-1 chemotherapy with radiotherapy at a total dose of 30 Gy is feasible and effective for patients with locally advanced OSCC, and that little or no histopathological response may be a risk factor for locoregional recurrence in this treatment. PMID:27123119

  17. Concomitant chemoradiotherapy with docetaxel and cisplatin followed by consolidation chemotherapy in locally advanced unresectable non-small cell lung cancer

    PubMed Central

    Eroglu, Celalettin; Orhan, Okan; Unal, Dilek; Dogu, Gamze G.; Karaca, Halit; Dikilitas, Mustafa; Oztürk, Ahmet; Ozkan, Metin; Kaplan, Bünyamin

    2013-01-01

    OBJECTIVES: To evaluate treatment results and toxicities in patients who received concomitant chemoradiotherapy (CRT) followed by consolidation with docetaxel and cisplatin in locally advanced unresectable non-small cell lung cancer (NSCLC). METHODS: Ninety three patients were included in this retrospective study. The patients received 66 Gy radiotherapy and weekly 20 mg/m2 docetaxel and 20 mg/m2 cisplatin chemotherapy concomitantly. One month later than the end of CRT, consolidation chemotherapy with four cycles of docetaxel 75 mg/m2 and cisplatin 75 mg/m2 were administered at each 21 days. RESULTS: Median age of the patients was 57 (range, 30-74). Following concomitant CRT, 14 patients (15%) showed complete and 50 patients (54%) showed partial response (total response rate was 69%). The median follow-up was 13 months (range: 2-51 months). The median overall survival was 18 months (95% confidential interval [CI]: 13.8-22.1 months); local control was 15 months (95% CI: 9.3-20.6 months); progression-free survival was 9 months (95% CI: 6.5-11.4 months). Esophagitis in eight (9%) patients, neutropenia in seven (8%) patients and pneumonitis in eight (9%) patients developed as grade III-IV toxicity due to concomitant CRT. CONCLUSION: Concomitant CRT with docetaxel and cisplatin followed by docetaxel and cisplatin consolidation chemotherapy might be considered as a feasible, and well tolerated treatment modality with high response rates despite the fact that it has not a survival advantage in patients with locally advanced unresectable NSCLC. PMID:23741274

  18. Advancing High Current Startup via Localized Helicity Injection in the PEGASUS Toroidal Experiment

    NASA Astrophysics Data System (ADS)

    Hinson, E. T.; Barr, J. L.; Bongard, M. W.; Burke, M. G.; Fonck, R. J.; Perry, J. M.; Redd, A. J.; Schlossberg, D. J.

    2013-10-01

    Non-solenoidal startup via local helicity injection (LHI) and poloidal field induction is used to produce Ip = 0 . 17 MA tokamak discharges. Impurity contamination has been reduced to negligible levels by use of conical frustum cathode geometry and local scraper limiters. Attainable currents are governed by global limits of helicity and energy balance, and Taylor relaxation. A simple lumped parameter model based on these limits is used to project discharge evolution, and indicates that attaining 1 MA in NSTX-U will require LHI-driven effective loop voltages to dominate contributions from dLp / dt . This regime contrasts with results to date and will be tested at 0.3 MA in PEGASUS with a new integrated multi-injector array. Injector impedance characteristics are consistent with magnetically-limited regimes observed in higher-power foilless diodes. Bursts of MHD are measured on time scales of order ~ 100 μ s, and correlate with rapid equilibrium changes, discrete rises in Ip, redistribution of the toroidal current, ion heating (Ti ~ 1 keV), transient drops in injector voltage, and apparent n = 1 line-tied kink activity at the injector. NIMROD simulations of high-field-side HI discharges in PEGASUS are in qualitative agreement, suggesting Ip buildup results from inward propagating toroidal current loops created by intermittent reconnection of injected current streams. Work supported by US DOE Grant DE-FG02-96ER54375.

  19. Advances in Local Drug Release and Scaffolding Design to Enhance Cell Therapy for Diabetes.

    PubMed

    Bowers, Daniel T; Botchwey, Edward A; Brayman, Kenneth L

    2015-12-01

    Islet transplant is a curative treatment for insulin-dependent diabetes. However, challenges, including poor tissue survival and a lack of efficient engraftment, must be overcome. An encapsulating or scaffolding material can act as a vehicle for agents carefully chosen for the islet transplant application. From open porous scaffolds to spherical capsules and conformal coatings, greater immune protection is often accompanied by greater distances to microvasculature. Generating a local oxygen supply from the implant material or encouraging vessel growth through the release of local factors can create an oxygenated engraftment site. Intricately related to the vascularization response, inflammatory interaction with the cell supporting implant is a long-standing hurdle to material-based islet transplant. Modulation of the immune responses to the islets as well as the material itself must be considered. To match the post-transplant complexity, the release rate can be tuned to orchestrate temporal responses. Material degradation properties can be utilized in passive approaches or external stimuli and biological cues in active approaches. A combination of multiple carefully chosen factors delivered in an agent-specialized manner is considered by this review to improve the long-term function of islets transplanted in scaffolding and encapsulating materials. PMID:26192271

  20. Case studies from community coalitions: advancing local tobacco control policy in a preemptive state.

    PubMed

    Douglas, Malinda R; Manion, Candida A; Hall-Harper, Vanessa D; Terronez, Kristina M; Love, Corey A; Chan, Andie

    2015-01-01

    Policies that shield people from the harm of tobacco exposure are essential to protect the health of the population. Coalitions have often led the way in safeguarding community health by promoting social norm change though policy adoption. In some states, tobacco control laws are weak, in part because of a tobacco industry tactic of prohibiting or pre-empting communities from enacting ordinances that are more protective. In spite of strong state-level preemptions, local coalitions in Oklahoma have implemented hundreds of voluntary policies in tobacco control that have improved the protection and health of their communities while not violating preemption. Three case studies of policy change are presented that exemplify the key approach of local coalitions working with strong allies and informed decision makers to establish tobacco-free businesses, schools, and outdoor recreational areas. In each of the cases, the policy changes surpassed the protection provided by the state laws and inspired additional policy changes. The key strategies and lessons learned may help tobacco control coalitions in other states limited by preemption to garner more support and momentum for important policy changes within their communities and states. PMID:25528703

  1. Interventional therapies for hepatocellular carcinoma

    PubMed Central

    Francis, Isaac R.; Novelli, Paula M.; Vellody, Ranjith; Pandya, Amit; Krishnamurthy, V.N.

    2012-01-01

    Abstract Hepatocellular carcinoma is the third most common cause of cancer-related death. In the past few years, staging systems have been developed that enable patients to be stratified into treatment algorithms in a multidisciplinary setting. Several of these treatments involve minimally invasive image-guided therapy that can be performed by radiologists. PMID:22487698

  2. Hepatocellular Carcinoma: Current Management and Future Development—Improved Outcomes with Surgical Resection

    PubMed Central

    Kishi, Yoji; Hasegawa, Kiyoshi; Sugawara, Yasuhiko; Kokudo, Norihiro

    2011-01-01

    Currently, surgical resection is the treatment strategy offering the best long-term outcomes in patients with hepatocellular carcinoma (HCC). Especially for advanced HCC, surgical resection is the only strategy that is potentially curative, and the indications for surgical resection have expanded concomitantly with the technical advances in hepatectomy. A major problem is the high recurrence rate even after curative resection, especially in the remnant liver. Although repeat hepatectomy may prolong survival, the suitability may be limited due to multiple tumor recurrence or background liver cirrhosis. Multimodality approaches combining other local ablation or systemic therapy may help improve the prognosis. On the other hand, minimally invasive, or laparoscopic, hepatectomy has become popular over the last decade. Although the short-term safety and feasibility has been established, the long-term outcomes have not yet been adequately evaluated. Liver transplantation for HCC is also a possible option. Given the current situation of donor shortage, however, other local treatments should be considered as the first choice as long as liver function is maintained. Non-transplant treatment as a bridge to transplantation also helps in decreasing the risk of tumor progression or death during the waiting period. The optimal timing for transplantation after HCC recurrence remains to be investigated. PMID:21994868

  3. Image-guided ablation for hepatocellular carcinoma.

    PubMed

    Lencioni, Riccardo; Crocetti, Laura

    2013-01-01

    Image-guided ablation is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when surgical options-including resection and transplantation-are precluded. The term image-guided tumor ablation is defined as the direct application of chemical substances or sources of energy to a focal tumor in an attempt to achieve eradication or substantial tumor destruction. Over the past 25 years, several methods for local tumor destruction have been developed and clinically tested. Radiofrequency ablation (RFA) has shown superior anticancer effect and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials, and is currently established as the standard ablative modality. Nevertheless, novel thermal and nonthermal techniques for tumor ablation-including microwave ablation and irreversible electroporation-seem to have potential to improve the efficacy of RFA and are currently undergoing clinical investigation. PMID:22941021

  4. Clinical Trial of Prophylactic Extended-Field Carbon-Ion Radiotherapy for Locally Advanced Uterine Cervical Cancer (Protocol 0508)

    PubMed Central

    Wakatsuki, Masaru; Kato, Shingo; Kiyohara, Hiroki; Ohno, Tatsuya; Karasawa, Kumiko; Tamaki, Tomoaki; Ando, Ken; Tsujii, Hirohiko; Nakano, Takashi; Kamada, Tadashi; Shozu, Makio

    2015-01-01

    To evaluate the efficacy and the toxicity of prophylactic extended-field carbon-ion radiotherapy (C-ion RT, Protocol 0508) for locally advanced squamous cell carcinoma of the uterine cervix in phase I / II clinical trial. Between May 2006 and January 2012, 26 patients of Protocol 0508 were treated with C-ion RT. The numbers of patients with stage IIB, IIIB, and IVA disease were 13, 11, and 2, respectively. Twenty patients had pelvic lymph node metastases. Median tumor size was 6.1 cm (range, 4.0–10.0 cm). The treatment consisted of extended-field irradiation of 39.0 gray equivalents (GyE) in 13 fractions, and additional 15.0 GyE in 5 fractions was given to the gross tumor volume (GTV) and surrounding tissues. With regard to local boost, 18.0 GyE in 2 fractions was given to GTV only. Total dose to the cervical tumor was 72.0 GyE over 20 fractions. The median follow-up period was 37 months. Twenty-one patients had grade 1 or 2 acute gastrointestinal toxicity, but all patients completed the treatment on schedule. There were no grade 3 or higher late complications, with 8 patients having grade 1 or 2 toxicities, 1 had grade 2 gastrointestinal toxicity and 2 had grade 2 genitourinary toxicity. Four patients (15.4%) developed local recurrence, and 8 patients (30.8%) had distant metastases. The 2-year local control rate, progression-free survival rate and overall survival rate were 83.6%, 61.5% and 73.1%, respectively. There were no severe acute or late complications in this trial. Prophylactic extended-field C-ion RT for locally advanced squamous cell carcinoma of the uterine cervix was a safe treatment. Although the number of patients in this study was small, the results support further investigations to confirm the therapeutic efficacy and to avoid or reduce toxicity. Trial Registration UMIN-CTR UMIN000016169 PMID:25993047

  5. Split hyperfractionated accelerated radiation therapy and concomitant cisplatin for locally advanced head and neck carcinomas: A preliminary report

    SciTech Connect

    Arias, F.; Dominguez, M.A.; Illarramendi, J.J.

    1995-10-15

    The feasibility and activity of an intensive chemoradiotherapeutic scheme for patients with locally advanced squamous cell head and neck cancers were tested in a single institution Phase II pilot study. Between January 1990 and February 1992, 40 patients were entered into this trial. The treatment protocol consisted of split hyperfractionated accelerated radiation therapy (SHART), 1.6 Gy per fraction given twice per day to a total dose of 64-67.2 Gy for a total of 6 weeks with a 2-week gap, and cisplatin (20 mg/sqm/Days 1 to 5, in continuous perfusion) concomitantly. All of the 40 patients are evaluable for response and survival. Toxicity was significant, but tolerable. A complete tumor response to this treatment was achieved by 37 patients (92.5%). With a minimal follow-up of 22 months (median 30 months) there have been 16 local relapses and 19 patients have died, 2 without tumor. The projected 2- and 3-year overall survival rates are 64% (confidence interval (CI) 95%, 49-79%) and 47%, respectively. The 2-year local control probability has been 56% (CI 95, 39-73%). This treatment obtains a high rate of complete responses with increased acute toxicity but tolerable late effects. Preliminary results are encouraging for laryngeal neoplasms. A longer follow-up is needed to evaluate the impact of this treatment on patient survival. 47 refs., 3 figs., 3 tabs.

  6. Having Your Cake and Eating It Too: Combining SBRT and Multi-agent Chemotherapy in Locally Advanced Pancreatic Cancer.

    PubMed

    Kishan, Amar; Lee, Percy

    2016-01-01

    We read with great interest the results of the LAP07 study comparing capecitabine-based chemoradiation with gemcitabine-based therapy for non-progressive locally advanced pancreatic cancer (LAPC), following four months of gemcitabine-based therapy. The results, consistent with previous data, showed that standard chemoradiation improves local control (LC) but not overall survival. In this brief editorial, we emphasize that LC may still be very important in LAPC, as up to 30% of patients with LAPC may die from locally progressive disease. This is particularly likely to be true as systemic therapies continue to improve in efficacy. We very briefly review the data in support of stereotactic body radiotherapy (SBRT) for LAPC, which has been shown to offer excellent LC with minimal late grade ≥ 2 toxicity rate in a recent multi-institutional phase II study. We underscore that  a short course of SBRT offers an expeditious alternative to a long course of chemoradiation, allowing the use of fully-intensive systemic therapy. PMID:27555984

  7. Local Tumor Treatment in Combination with Systemic Ipilimumab Immunotherapy Prolongs Overall Survival in Patients with Advanced Malignant Melanoma.

    PubMed

    Theurich, Sebastian; Rothschild, Sacha I; Hoffmann, Michael; Fabri, Mario; Sommer, Andrea; Garcia-Marquez, Maria; Thelen, Martin; Schill, Catherine; Merki, Ramona; Schmid, Thomas; Koeberle, Dieter; Zippelius, Alfred; Baues, Christian; Mauch, Cornelia; Tigges, Christian; Kreuter, Alexander; Borggrefe, Jan; von Bergwelt-Baildon, Michael; Schlaak, Max

    2016-09-01

    Immune checkpoint inhibition with ipilimumab has revolutionized cancer immunotherapy and significantly improved outcomes of patients with advanced malignant melanoma. Local peripheral treatments (LPT), such as radiotherapy or electrochemotherapy, have been shown to modulate systemic immune responses, and preliminary data have raised the hypothesis that the combination of LPT with systemic immune checkpoint blockade might be beneficial. Clinical data from 127 consecutively treated melanoma patients at four cancer centers in Germany and Switzerland were analyzed. Patients received either ipilimumab (n = 82) or ipilimumab and additional LPT (n = 45) if indicated for local tumor control. The addition of LPT to ipilimumab significantly prolonged overall survival (OS; median OS 93 vs. 42 weeks, unadjusted HR, 0.46; P = 0.0028). Adverse immune-related events were not increased by the combination treatment, and LPT-induced local toxicities were in most cases mild. In a multivariable Cox regression analysis, we show that the effect of added LPT on OS remained statistically significant after adjusting for BRAF status, tumor stage, tumor burden, and central nervous system metastases (adjusted HR, 0.56; 95% confidence interval, 0.31-1.01, P = 0.05). Our data suggest that the addition of LPT to ipilimumab is safe and effective in patients with metastatic melanoma irrespective of clinical disease characteristics and known risk factors. Induction of antitumor immune responses is most likely the underlying mechanism and warrants prospective validation. Cancer Immunol Res; 4(9); 744-54. ©2016 AACR. PMID:27466265

  8. Having Your Cake and Eating It Too: Combining SBRT and Multi-agent Chemotherapy in Locally Advanced Pancreatic Cancer

    PubMed Central

    Lee, Percy

    2016-01-01

    We read with great interest the results of the LAP07 study comparing capecitabine-based chemoradiation with gemcitabine-based therapy for non-progressive locally advanced pancreatic cancer (LAPC), following four months of gemcitabine-based therapy. The results, consistent with previous data, showed that standard chemoradiation improves local control (LC) but not overall survival. In this brief editorial, we emphasize that LC may still be very important in LAPC, as up to 30% of patients with LAPC may die from locally progressive disease. This is particularly likely to be true as systemic therapies continue to improve in efficacy. We very briefly review the data in support of stereotactic body radiotherapy (SBRT) for LAPC, which has been shown to offer excellent LC with minimal late grade ≥ 2 toxicity rate in a recent multi-institutional phase II study. We underscore that  a short course of SBRT offers an expeditious alternative to a long course of chemoradiation, allowing the use of fully-intensive systemic therapy.  PMID:27555984

  9. A Challenging Surgical Approach to Locally Advanced Primary Urethral Carcinoma: A Case Report and Literature Review.

    PubMed

    Lucarelli, Giuseppe; Spilotros, Marco; Vavallo, Antonio; Palazzo, Silvano; Miacola, Carlos; Forte, Saverio; Matera, Matteo; Campagna, Marcello; Colamonico, Ottavio; Schiralli, Francesco; Sebastiani, Francesco; Di Cosmo, Federica; Bettocchi, Carlo; Di Lorenzo, Giuseppe; Buonerba, Carlo; Vincenti, Leonardo; Ludovico, Giuseppe; Ditonno, Pasquale; Battaglia, Michele

    2016-05-01

    Primary urethral carcinoma (PUC) is a rare and aggressive cancer, often underdetected and consequently unsatisfactorily treated. We report a case of advanced PUC, surgically treated with combined approaches.A 47-year-old man underwent transurethral resection of a urethral lesion with histological evidence of a poorly differentiated squamous cancer of the bulbomembranous urethra. Computed tomography (CT) and bone scans excluded metastatic spread of the disease but showed involvement of both corpora cavernosa (cT3N0M0). A radical surgical approach was advised, but the patient refused this and opted for chemotherapy. After 17 months the patient was referred to our department due to the evidence of a fistula in the scrotal area. CT scan showed bilateral metastatic disease in the inguinal, external iliac, and obturator lymph nodes as well as the involvement of both corpora cavernosa. Additionally, a fistula originating from the right corpus cavernosum extended to the scrotal skin. At this stage, the patient accepted the surgical treatment, consisting of different phases. Phase I: Radical extraperitoneal cystoprostatectomy with iliac-obturator lymph nodes dissection. Phase II: Creation of a urinary diversion through a Bricker ileal conduit. Phase III: Repositioning of the patient in lithotomic position for an overturned Y skin incision, total penectomy, fistula excision, and "en bloc" removal of surgical specimens including the bladder, through the perineal breach. Phase IV: Right inguinal lymphadenectomy.The procedure lasted 9-and-a-half hours, was complication-free, and intraoperative blood loss was 600 mL. The patient was discharged 8 days after surgery. Pathological examination documented a T4N2M0 tumor. The clinical situation was stable during the first 3 months postoperatively but then metastatic spread occurred, not responsive to adjuvant chemotherapy, which led to the patient's death 6 months after surgery.Patients with advanced stage tumors of the

  10. Selecting Patients With Locally Advanced Rectal Cancer for Neoadjuvant Treatment Strategies

    PubMed Central

    Dewdney, Alice; Cunningham, David

    2013-01-01

    Rectal cancer remains a significant problem worldwide. Outcomes vary significantly according to the stage of disease and prognostic factors, including the distance of the tumor from the circumferential resection margin. Accurate staging, including high-resolution magnetic resonance imaging, allows stratification of patients into low-, moderate-, and high-risk disease; this information can be used to inform multidisciplinary team decisions regarding the role of neoadjuvant therapy. Both neoadjuvant short-course radiotherapy and long-course chemoradiation reduce the risk of local recurrence compared with surgery alone, but they have little impact on survival. Although there remains a need to reduce overtreatment of those patients at moderate risk, evaluation of intensified regimens for those with high-risk disease is still required to reduce distant failure rates and improve survival in these patients with an otherwise poor prognosis. PMID:23821325

  11. A Novel Murine Model for Localized Radiation Necrosis and its Characterization Using Advanced Magnetic Resonance Imaging

    SciTech Connect

    Jost, Sarah C.; Hope, Andrew; Kiehl, Erich; Perry, Arie; Travers, Sarah; Garbow, Joel R.

    2009-10-01

    Purpose: To develop a murine model of radiation necrosis using fractionated, subtotal cranial irradiation; and to investigate the imaging signature of radiation-induced tissue damage using advanced magnetic resonance imaging techniques. Methods and Materials: Twenty-four mice each received 60 Gy of hemispheric (left) irradiation in 10 equal fractions. Magnetic resonance images at 4.7 T were subsequently collected using T1-, T2-, and diffusion sequences at selected time points after irradiation. After imaging, animals were killed and their brains fixed for correlative histologic analysis. Results: Contrast-enhanced T1- and T2-weighted magnetic resonance images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 {mu}m{sup 2}/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 {mu}m{sup 2}/ms) (p < 0.0001). Histology reflected changes typically seen in radiation necrosis. Conclusions: This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that diffusion-weighted imaging may be helpful in answering this diagnostic question in clinical settings.

  12. Changes in allelic imbalances in locally advanced breast cancers after chemotherapy

    PubMed Central

    Varna, M; Soliman, H; Feugeas, J-P; Turpin, E; Chapelin, D; Legrès, L; Plassa, L-F; de Roquancourt, A; Espié, M; Misset, J-L; Janin, A; de Thé, H; Bertheau, P

    2007-01-01

    In advanced breast cancers, TP53 mutation is highly predictive of complete response to high-dose epirubicin/cyclophosphamide chemotherapy. In these tumours with an altered control of genomic stability, accumulation of chemotherapy-induced genetic alterations may contribute to cell death and account for complete response. To explore the effects of chemotherapy on stability of the tumour genome, allelic profiles were obtained from microdissected tumour samples before and after chemotherapy in 29 unresponsive breast cancers (9 with TP53 mutation). Ninety-four per cent allelic profiles remained unchanged after treatment. Interestingly, 11 profiles (6%) showed important changes after treatment; allelic imbalances significantly increased (four cases) or decreased (seven cases) after chemotherapy in three distinct experiments, two of which using laser microdissected tumour cells. These genetic changes were not linked to the TP53 status, but one tumour showed complete disappearance of TP53-mutated cells in the residual tumour after treatment. Altogether, these observations carry important implications for the clonal evolution of breast cancers treated with DNA-damaging agents, as they point both to the importance of tumour heterogeneity and chemotherapy-driven selection of subclones. PMID:17876337

  13. Preoperative induction therapy for locally advanced thymic tumors: a retrospective analysis using the ChART database

    PubMed Central

    Wei, Yucheng; Gu, Zhitao; Fu, Jianhua; Tan, Liejie; Zhang, Peng; Han, Yongtao; Chen, Chun; Zhang, Renquan; Li, Yin; Chen, Keneng; Chen, Hezhong; Liu, Yongyu; Cui, Youbing; Wang, Yun; Pang, Liewen; Yu, Zhentao; Zhou, Xinming; Liu, Yangchun; Liu, Yuan

    2016-01-01

    Background To evaluate the role of preoperative induction therapy on prognosis of locally advanced thymic malignancies. Methods Between 1994 and 2012, patients received preoperative induction therapies (IT group) in the Chinese Alliance for Research in Thymomas (ChART) database, were compared with those having surgery directly after preoperative evaluation (DS group). All tumors receiving induction therapies were locally advanced (clinically stage III–IV) before treatment and those turned out to be in pathological stage I and II were considered downstaged by induction. Clinical pathological characteristics were retrospectively analyzed. To more accurately study the effect of induction therapies, stage IV patients were then excluded. Only stage I-III tumors in the IT group and stage III cases in the DS group were selected for further comparison in a subgroup analysis. Results Only 68 (4%) out of 1,713 patients had induction therapies, with a R0 resection of 67.6%, 5-year recurrence of 44.9%, and 5- and 10-year overall survivals (OS) of 49.7% and 19.9%. Seventeen patients (25%) were downstaged after induction. Significantly more thymomas were downstaged than thymic carcinomas (38.7% vs. 13.9%, P=0.02). Tumors downstaged after induction had significantly higher 5-year OS than those not downstaged (93.8% vs. 35.6%, P=0.013). For the subgroup analysis when stage IV patients were excluded, 5-year OS was 85.2% in the DS group and 68.1% in the IT group (P=0.000), although R0 resection were similar (76.4% vs. 73.3%, P=0.63). However, 5-year OS in tumors downstaged after induction (93.8%) was similar to those in the DS group (85.2%, P=0.438), both significantly higher than those not downstaged after induction (35.6%, P=0.000). Conclusions Preoperative neoadjuvant therapy have been used only occasionally in locally advanced thymic malignances. Effective induction therapy leading to tumor downstaging may be beneficial for potentially unresectable diseases, especially in

  14. A Novel Murine Model for Localized Radiation Necrosis and its Characterization using Advanced Magnetic Resonance Imaging

    PubMed Central

    Jost, Sarah C.; Hope, Andrew; Kiehl, Erich; Perry, Arie; Travers, Sarah; Garbow, Joel R.

    2013-01-01

    Introduction Magnetic resonance (MR) images following external beam radiotherapy for brain tumors often display signal changes characteristic of either tumor progression and/or radiation injury. No non-invasive diagnostic biomarkers have been identified that clearly distinguish between these two disease processes. This study’s objective was to develop a murine model of radiation necrosis using fractionated, sub-total cranial irradiation and to investigate the imaging signature of radiation-induced tissue damage using advanced MR imaging techniques. Methods Twenty four mice each received 60 Gy of hemispheric (left) irradiation in ten equal fractions. MR images at 4.7 T were subsequently collected using T1-, T2- and diffusion-sequences at selected time points following irradiation or implantation. Following imaging, animals were euthanized and their brains were fixed for correlative histology. Results Contrast-enhanced T1- and T2-weighted MR images at months 2, 3, and 4 showed changes consistent with progressive radiation necrosis. Quantitatively, mean diffusivity was significantly higher (mean = 0.86, 1.13, and 1.24 μm2/ms at 2, 3, and 4 months, respectively) in radiated brain, compared with contralateral untreated brain tissue (mean = 0.78, 0.82, and 0.83 μm2/ms) (p<0.0001). Histology reflected changes typically seen in radiation necrosis. Conclusions This murine model of radiation necrosis will facilitate investigation of imaging biomarkers that distinguish between radiation necrosis and tumor recurrence. In addition, this preclinical study supports clinical data suggesting that DWI may be helpful in answering this diagnostic question in clinical settings. PMID:19735877

  15. Sequence of treatment in locally advanced and metastatic renal cell carcinoma

    PubMed Central

    Fischer, Stefanie; Gillessen, Silke

    2015-01-01

    The spectrum of drugs that have shown activity in advanced or metastatic renal cell carcinoma (RCC) has led to a debate on the optimal sequence of treatments. There is agreement on recommending targeted agents as the standard of care in this disease. Uncertainty, however, remains on the best first-line drug choice. Physicians and patients may select sunitinib, bevacizumab in combination with interferon-alpha (IFN-α), pazopanib, or—in poor risk patients—temsirolimus. There are also a variety of therapies with proven efficacy on hand in the second-line setting: sorafenib, pazopanib, axitinib, and everolimus. While most randomized RCC trials assessed progression free survival (PFS) as primary endpoint, some agents were shown to improve median overall survival (OS), and given in sequence they have extended the life expectancy of RCC patients from 13 months in the cytokine era to over 30 months. Despite the progress made, there are sobering aspects to the oncologic success story in RCC, as the new treatments do not obtain an objective response or disease stabilization (SD) in all patients. There are also as yet no predictors to select patients who might benefit and those who are primary resistant to specific drugs, and ultimately almost all patients will experience disease progression. Bearing inevitable treatment failure in mind, availability of further drugs and switching therapy while the patient is in a condition to continue pharmacotherapy is essential. Of note, depending on the setting, only 33-59% of patients receive second-line treatment. In this review we present data on first-, second-, and third-line treatment in RCC, and discuss the difficulties in their interpretation in the context of treatment sequence. We summarize biological aspects and discuss mechanisms of resistance to anti-angiogenic therapy and their implications for treatment selection. PMID:26816832

  16. Phase II study of preoperative paclitaxel/cisplatin with radiotherapy in locally advanced esophageal cancer

    SciTech Connect

    Kim, Dong W.; Blanke, Charles D.; Wu, Huiyun; Shyr, Yu; Berlin, Jordan; Beauchamp, R. Daniel; Chakravarthy, Bapsi . E-mail: bapsi.chak@vanderbilt.edu

    2007-02-01

    Purpose: Preoperative paclitaxel-based chemoradiotherapy may improve the response rates and survival in patients with localized esophageal cancer. We evaluated paclitaxel-based induction chemoradiotherapy in patients with localized esophageal cancer to determine its feasibility, clinical response, pathologic response, and overall survival. Methods and Materials: Between 1995 and 1998, 50 patients were enrolled in this study. At study entry, patients were categorized as either resectable or unresectable according to evaluation by an experienced thoracic surgeon. All patients were treated with paclitaxel 175 mg/m{sup 2} and cisplatin 75 mg/m{sup 2} on Day 1, 29 with radiotherapy to 3,000 cGy in 15 fractions. Resectable patients underwent esophagectomy 4 weeks later. Postoperatively, patients received two cycles of paclitaxel 175 mg/m{sup 2} on Day 1 and 5-fluorouracil 350 mg/m{sup 2} and leucovorin 300 mg on Days 1-3, given every 28 days. Patients who were deemed unsuitable for resection from the outset continued radiotherapy to a total dose of 6,000 cGy. Results: Of the 50 patients, all began neoadjuvant chemoradiotherapy, 40 patients underwent surgery, and 25 patients completed postoperative chemotherapy. A pathologic complete response was seen in 7 patients (17.5%). Patients with a pathologic response had a median survival of 32.4 months vs. 14.4 months for nonresponders (p <0.001). Patients with a clinical response had a median survival of 25.2 months compared with 15.6 months for nonresponders (p = 0.002). At a median follow up of 19.8 months (range 2.4-100.8), the median survival was 20.4 months and the 3-year overall survival rate was 23.2%. Conclusion: Although preoperative cisplatin/paclitaxel with 3,000 cGy was tolerable, this multimodality regimen did not appear to be superior to standard cisplatin/5-fluorouracil-containing regimens and its use is not recommended.

  17. Ablation of the locally advanced pancreatic cancer: An introduction and brief summary of techniques.

    PubMed

    Petrou, Athanasios; Moris, Demetrios; Paul Tabet, Patrick; David Wensley Richards, Brian; Kourounis, Georgios

    2016-01-01

    Pancreatic ductal adenocarcinoma is a lethal and late presenting malignancy with dismal survival rates. An estimated total of 330,000 people died from this malignancy in 2012. Although there have been improvements in diagnostic and treatment methods, the survival of late stage pancreatic cancer has not shown significant improvement in the past 4 decades. Multiple treatment approaches are available including chemotherapy, radiotherapy, and immunotherapy, but to this day surgical resection remains the only curative treatment option. Ablative techniques use various forms of energy to cause local tissue destruction through necrosis or apoptosis. They are relevant in pancreatic ductal adenocarcinoma as they are a treatment option in non-resectable tumors where their use ranges from symptom control to reducing tumor size for resection. In this narrative review we have grouped and outlined the various ablative methods, classifying them into thermal (Radiofrequency ablation, Microwave ablation, High Intensity Focused Ultrasound ablation,