scholarly journals Radiotherapy in the treatment of gastrointestinal stromal tumor

Rare Tumors ◽  
2011 ◽  
Vol 3 (4) ◽  
pp. 111-113 ◽  
Author(s):  
Christin A. Knowlton ◽  
Luther W. Brady ◽  
Rebecca C. Heintzelman
Keyword(s):  
Kinase Inhibitor ◽  
Standard Of Care ◽  
High Rate ◽  
Viable Option ◽  
Current Standard ◽  
Mesenchymal Tumors ◽  
Palliative Setting ◽  
Term Response

Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. Up to one-third of GISTs are malignant with a high rate of metastasis. Surgical resection is the mainstay of care for patients with resectable disease. Imatinib mesylate, a selective tyrosine kinase inhibitor, is the current standard of care for GISTs that cannot be completely resected or in cases of metastatic GIST. Although often overlooked, radiation therapy is a viable option for select patients with GIST. We report the case of a patient with unresectable GIST who was treated with local radiotherapy and achieved long-term response. We also present a review of the literature regarding the use of radiotherapy in the treatment of GIST. GIST has been shown to be a radiosensitive tumor. Radiotherapy can offer long-term local control and should be considered in the adjuvant or palliative setting. The role of radiotherapy delivered concurrently with imatinib in the treatment of GIST may warrant further investigation.

scholarly journals PDTM-44. ROLE OF ONC-206 IN REGULATING MEDULLOBLASTOMA TUMOR PROGRESSION

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi196-vi197
Author(s):  
Anshu Malhotra ◽  
Jingbo Liu ◽  
Tobey MacDonald
Keyword(s):  
Cell Lines ◽  
Small Molecule ◽  
Standard Of Care ◽  
Clinical Results ◽  
Current Standard ◽  
Survival Pathways ◽  
Cognitive Deficiencies ◽  
G Protein Coupled

Abstract Medulloblastoma (MB) is the most common malignant brain tumor in children. Of the four different sub-groups, the Sonic Hedgehog (SHH) subgroup accounts for about 30% of human MBs. The current standard of care (resection, cranio-spinal irradiation, and chemotherapy) for MB is typically ineffective for SHH MB in non-infants and those with metastatic disease. Survivors are frequently beset with long-term side effects including cognitive deficiencies and a severely impaired quality of life. Taken together, there is a critical need for novel targeted therapies for SHH MB. Recently, promising preclinical and clinical results have been obtained in a variety of cancers treated with a small molecule antagonist, ONC-201, which acts against DRD2, a G-protein coupled receptor that is widely expressed in MBs and regulates pro-survival pathways in tumors. In the present study we report the activity of ONC-201 and another DRD2 antagonist, ONC-206, which binds DRD2 with increased affinity. We tested three different MB cell lines with varied levels of DRD2 expression against these drugs, and consistently observed increased cell death at lower doses of ONC-206 compared to ONC-201. Following literature reports about the mechanism of action of ONC-201, we also evaluated the role of ClpP gene in MB cell lines. ClpP is a mitochondrial protease that has been shown to directly bind ONC 201. We observed a decrease in the expression of this gene after treatment of MB cell lines with ONC-206. Current studies are focusing on exploring the mechanism by which ONC-206 affects MB growth and metastasis. Dissecting this mechanism will be pivotal in predicting the role of this small molecule as a pre-clinical therapeutic for MB treatment.

scholarly journals Role of Surgery in Clostridium difficile Infection

2020 ◽  
Vol 33 (02) ◽  
pp. 087-091 ◽  
Author(s):  
Aela Vely ◽  
Paula Ferrada
Keyword(s):  
Colonic Mucosa ◽  
Loop Ileostomy ◽  
Standard Of Care ◽  
Acute Illness ◽  
Viable Option ◽  
Current Standard ◽  
Clostridioides Difficile ◽  
Clostridioides Difficile Infection ◽  
Early Decision

Abstract Clostridium (reclassified as “Clostridioides”) difficile infection (CDI) occurs as a chronic or an acute illness with intensity varying from mild to severe. Although most cases of CDI can be managed with antibiotics and supportive care, when the patient presents with fulminant disease, the early decision to perform surgery is imperative for survival. The current standard of care is the subtotal colectomy. However, loop ileostomy with vancomycin enemas delivered into the colonic mucosa has been described as a viable option on selected patients.

scholarly journals The Yin and the Yang of Treatment for Chronic Hepatitis B—When to Start, When to Stop Nucleos(t)ide Analogue Therapy

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 934 ◽  
Author(s):  
Samuel Hall ◽  
Jessica Howell ◽  
Kumar Visvanathan ◽  
Alexander Thompson
Keyword(s):  
Chronic Hepatitis ◽  
Hepatitis B ◽  
Chronic Hepatitis B ◽  
Antiviral Agents ◽  
Standard Of Care ◽  
Current Standard ◽  
Hbsag Loss ◽  
Personalised Treatment ◽  
Treat All

Over 257 million individuals worldwide are chronically infected with the Hepatitis B Virus (HBV). Nucleos(t)ide analogues (NAs) are the first-line treatment option for most patients. Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are both potent, safe antiviral agents, have a high barrier to resistance, and are now off patent. They effectively suppress HBV replication to reduce the risk of cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Treatment is continued long-term in most patients, as NA therapy rarely induces HBsAg loss or functional cure. Two diverging paradigms in the treatment of chronic hepatitis B have recently emerged. First, the public health focussed “treat-all” strategy, advocating for early and lifelong antiviral therapy to minimise the risk of HCC as well as the risk of HBV transmission. In LMICs, this strategy may be cost saving compared to monitoring off treatment. Second, the concept of “stopping” NA therapy in patients with HBeAg-negative disease after long-term viral suppression, a personalised treatment strategy aiming for long-term immune control and even HBsAg loss off treatment. In this manuscript, we will briefly review the current standard of care approach to the management of hepatitis B, before discussing emerging evidence to support both the “treat-all” strategy, as well as the “stop” strategy, and how they may both have a role in the management of patients with chronic hepatitis B.

scholarly journals Towards Personalization in the Curative Treatment of Gastric Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Astrid E. Slagter ◽  
Marieke A. Vollebergh ◽  
Edwin P. M. Jansen ◽  
Johanna W. van Sandick ◽  
Annemieke Cats ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Molecular Characteristics ◽  
Perioperative Chemotherapy ◽  
Current Standard ◽  
Common Cancer ◽  
Resectable Gastric Cancer

Gastric cancer is the fifth most common cancer worldwide and has a high mortality rate. In the last decades, treatment strategy has shifted from an exclusive surgical approach to a multidisciplinary strategy. Treatment options for patients with resectable gastric cancer as recommended by different worldwide guidelines, include perioperative chemotherapy, pre- or postoperative chemoradiotherapy and postoperative chemotherapy. Although gastric cancer is a heterogeneous disease with respect to patient-, tumor-, and molecular characteristics, the current standard of care is still according to a one-size-fits-all approach. In this review, we discuss the background of the different treatment strategies in resectable gastric cancer including the current standard, the specific role of radiotherapy, and describe the current areas of research and potential strategies for personalization of therapy.

scholarly journals Radiotherapy of glioblastoma 15 years after the landmark Stupp’s trial: more controversies than standards?

2018 ◽  
Vol 52 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Tomas Kazda ◽  
Adam Dziacky ◽  
Petr Burkon ◽  
Petr Pospisil ◽  
Marek Slavik ◽  
...  
Keyword(s):  
Concurrent Chemoradiotherapy ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Current Standard ◽  
Tumor Treating Fields ◽  
Integrated Boost ◽  
Hippocampal Sparing ◽  
New Treatment ◽  
Personalized Approach

Abstract Background The current standard of care of glioblastoma, the most common primary brain tumor in adults, has remained unchanged for over a decade. Nevertheless, some improvements in patient outcomes have occurred as a consequence of modern surgery, improved radiotherapy and up-to-date management of toxicity. Patients from control arms (receiving standard concurrent chemoradiotherapy and adjuvant chemotherapy with temozolomide) of recent clinical trials achieve better outcomes compared to the median survival of 14.6 months reported in Stupp’s landmark clinical trial in 2005. The approach to radiotherapy that emerged from Stupp’s trial, which continues to be a basis for the current standard of care, is no longer applicable and there is a need to develop updated guidelines for radiotherapy within the daily clinical practice that address or at least acknowledge existing controversies in the planning of radiotherapy. The goal of this review is to provoke critical thinking about potentially controversial aspects in the radiotherapy of glioblastoma, including among others the issue of target definitions, simultaneously integrated boost technique, and hippocampal sparing. Conclusions In conjunction with new treatment approaches such as tumor-treating fields (TTF) and immunotherapy, the role of adjuvant radiotherapy will be further defined. The personalized approach in daily radiotherapy practice is enabled with modern radiotherapy systems.

scholarly journals Radiomics for the Diagnosis and Differentiation of Pancreatic Cystic Lesions

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 505
Author(s):  
Jorge D. Machicado ◽  
Eugene J. Koay ◽  
Somashekar G. Krishna
Keyword(s):  
Predictive Accuracy ◽  
Quantitative Imaging ◽  
Standard Of Care ◽  
Small Sample ◽  
Cystic Lesions ◽  
Current Standard ◽  
Cross Sectional ◽  
Small Sample Sizes ◽  
Insight Into

Radiomics, also known as quantitative imaging or texture analysis, involves extracting a large number of features traditionally unmeasured in conventional radiological cross-sectional images and converting them into mathematical models. This review describes this approach and its use in the evaluation of pancreatic cystic lesions (PCLs). This discipline has the potential of more accurately assessing, classifying, risk stratifying, and guiding the management of PCLs. Existing studies have provided important insight into the role of radiomics in managing PCLs. Although these studies are limited by the use of retrospective design, single center data, and small sample sizes, radiomic features in combination with clinical data appear to be superior to the current standard of care in differentiating cyst type and in identifying mucinous PCLs with high-grade dysplasia. Combining radiomic features with other novel endoscopic diagnostics, including cyst fluid molecular analysis and confocal endomicroscopy, can potentially optimize the predictive accuracy of these models. There is a need for multicenter prospective studies to elucidate the role of radiomics in the management of PCLs.

scholarly journals Simulated retreat of Jakobshavn Isbræ since the Little Ice Age controlled by geometry

2018 ◽  
Vol 12 (7) ◽  
pp. 2249-2266 ◽  
Author(s):  
Nadine Steiger ◽  
Kerim H. Nisancioglu ◽  
Henning Åkesson ◽  
Basile de Fleurian ◽  
Faezeh M. Nick
Keyword(s):  
Little Ice Age ◽  
Ice Age ◽  
Climate Forcing ◽  
Relative Role ◽  
Regional Warming ◽  
History Of ◽  
The Impact ◽  
Term Response

Abstract. Rapid retreat of Greenland's marine-terminating glaciers coincides with regional warming trends, which have broadly been used to explain these rapid changes. However, outlet glaciers within similar climate regimes experience widely contrasting retreat patterns, suggesting that the local fjord geometry could be an important additional factor. To assess the relative role of climate and fjord geometry, we use the retreat history of Jakobshavn Isbræ, West Greenland, since the Little Ice Age (LIA) maximum in 1850 as a baseline for the parameterization of a depth- and width-integrated ice flow model. The impact of fjord geometry is isolated by using a linearly increasing climate forcing since the LIA and testing a range of simplified geometries. We find that the total length of retreat is determined by external factors – such as hydrofracturing, submarine melt and buttressing by sea ice – whereas the retreat pattern is governed by the fjord geometry. Narrow and shallow areas provide pinning points and cause delayed but rapid retreat without additional climate warming, after decades of grounding line stability. We suggest that these geometric pinning points may be used to locate potential sites for moraine formation and to predict the long-term response of the glacier. As a consequence, to assess the impact of climate on the retreat history of a glacier, each system has to be analyzed with knowledge of its historic retreat and the local fjord geometry.

scholarly journals How I treat atypical chronic myeloid leukemia

Blood ◽  
2017 ◽  
Vol 129 (7) ◽  
pp. 838-845 ◽  
Author(s):  
Jason Gotlib
Keyword(s):  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasm ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
High Rate ◽  
Current Standard ◽  
Hematopoietic Stem ◽  
Genetic Features ◽  
Atypical Chronic Myeloid Leukemia

Abstract Atypical chronic myeloid leukemia, BCR-ABL1 negative (aCML) is a rare myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) for which no current standard of care exists. The challenges of aCML relate to its heterogeneous clinical and genetic features, high rate of transformation to acute myeloid leukemia, and historically poor survival. Therefore, allogeneic hematopoietic stem cell transplantation should always be an initial consideration for eligible patients with a suitable donor. Nontransplant approaches for treating aCML have otherwise largely relied on adopting treatment strategies used for MDS and MPN. However, such therapies, including hypomethylating agents, are based on a paucity of data. With an eye toward making a more meaningful impact on response rates and modification of the natural history of the disease, progress will rely on enrollment of patients into clinical trials and molecular profiling of individuals so that opportunities for targeted therapy can be exploited.

Adjuvant Treatments for Localized Advanced Gastric Cancer: Differences among Geographic Regions

2012 ◽  
pp. e31-e34
Author(s):  
Yoon-Koo Kang ◽  
Changhoon Yoo
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Therapy ◽  
Standard Of Care ◽  
Current Standard ◽  
The West ◽  
The United Kingdom ◽  
Group B ◽  
Leukemia Group ◽  
Postoperative Chemoradiation

Overview: After much debate, adjuvant therapy has become the standard of care worldwide for resected localized gastric cancer. However, geographic differences exist in standard adjuvant treatments: postoperative chemoradiation in North America, perioperative chemotherapy in the United Kingdom, and postoperative chemotherapy in East Asia. Now that D2 gastrectomy has been recognized as the optimal surgery for localized gastric cancer in the West as well as in Asia, the standard adjuvant treatments used in the West may need to be reconsidered. One of the most important issues in adjuvant therapy for localized gastric cancer is how to improve the clinical outcomes of current standard treatments. Recent Cancer and Leukemia Group B (CALGB) and AMC studies suggest that simply intensifying chemotherapy by adding more agents or prolonging treatment duration is insufficient. However, new strategies like early initiation of chemotherapy and/or intraperitoneal chemotherapy may further improve the current standard adjuvant therapy. In the era of targeted therapy, the role of biologic agents for gastric cancer should also be explored in the adjuvant setting. With a deeper understanding of the molecular biology of gastric cancer, adjuvant therapy for patients with localized gastric cancer can be optimized and individualized.

Treatment of glioblastoma in Venezuela: Limitations using the current standard of care

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13036-e13036
Author(s):  
E. I. Arbona-Roche ◽  
C. Sucre ◽  
R. Vera-Gimón ◽  
A. Vera-Gimón ◽  
R. Vera-Vera ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
High Rate ◽  
Phase Iii ◽  
Stevens Johnson Syndrome ◽  
Hematologic Toxicity ◽  
Current Standard ◽  
Johnson Syndrome ◽  
Newly Diagnosed Glioblastoma ◽  
Grade 3

e13036 Background: The EORTC/NCIC phase III clinical trial using chemoirradiation with temozolomide (TMZ) 75 mg m-2 x 42d, followed by adyuvant TMZ 150–200 mg m-2 daily x 5d q28d x six cycles set a new standard of care for newly diagnosed glioblastoma (GBM). The applicability of this regimen in developing countries can be problematic. Objectives: To review our experience in Venezuela, contrasting overall survival (OS), 6-month progression-free survival (6PFS), and toxicity in our patients with corresponding outcomes from the EORTC/NCIC trial. Methods: We treated 30 patients with this regimen from March 2001 through July 2004. Results: The median age was 51 years; 17 (60%) were men; 27 (90%) had biopsy or partial resection; 27 (90%) took prophylactic anticonvulsants; and 23 (77%) had prophylaxis against P. jiroveci. Most patients (83%) took the full TMZ treatment during radiation, 7% interrupted TMZ during RT, and 10% could not afford the drug. One patient had Stevens-Johnson syndrome and did not complete RT. Twelve (40%) patients had stereotactic radiosurgery for recurrent disease during the adjuvant phase. The 24-month OS was 30%, median OS was 7.5 months, median PFS was 5 months, and 6PFS was 41%. SRS did not have any effect on OS (p = 0.17, logrank). Grade 3–4 hematologic toxicity was seen in two patients (7%). Conclusions: Except for differences in median OS (7.1 mo) and in 6-PFS (12.6 percentage points) all other measures were reasonably close to the EORTC/NCIC trial. Of concern is the high rate of anticonvulsant prophylaxis using enzyme-inducing drugs and the difficult access to TMZ. No significant financial relationships to disclose.

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