FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2125146007> ?p ?o ?g. }

• W2125146007 endingPage "499" @default.
• W2125146007 startingPage "491" @default.
• W2125146007 abstract "You have accessJournal of UrologyAdult Urology1 Feb 2015Castration-Resistant Prostate Cancer: AUA Guideline Amendment Michael S. Cookson, William T. Lowrance, Mohammad H. Murad, and Adam S. Kibel Michael S. CooksonMichael S. Cookson More articles by this author , William T. LowranceWilliam T. Lowrance More articles by this author , Mohammad H. MuradMohammad H. Murad More articles by this author , and Adam S. KibelAdam S. Kibel Financial and/or other relationship with Dendreon and Sanofi Aventis. More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.10.104AboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail Abstract Purpose: The purpose of this amendment is to incorporate relevant newly-published literature to better provide a rational basis for the management of patients with castration-resistant prostate cancer. Materials and Methods: The original systematic review and meta-analysis of the published literature yielded 303 articles published from 1996 through 2013. This review formed a majority of the guideline statements. Clinical Principles and Expert Opinions were used for guideline statements lacking sufficient evidence-based data. In April 2014, the CRPC guideline underwent amendment based on a second comprehensive literature search, which retrieved additional studies published between February 2013 and February 2014. Thirty-seven studies from this search provided data relevant to the specific treatment modalities for CRPC. Results: Guideline statements based on six index patients developed to represent the most common scenarios encountered in clinical practice were amended appropriately. The additional literature provided the basis for an update of current supporting text as well as the incorporation of new guideline statements. Specifically, the addition of Radium-223 was placed in the guidelines related to the treatment of CRPC. Conclusions: Given the rapidly evolving nature of this field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient’s treatment goals. Patients’ preferences and personal goals should be considered when choosing management strategies. The newly incorporated evidence-based statements supplement the original guideline published in 2013, which provided guidance for the treatment of men with CRPC. This guideline will be continually updated as new literature emerges in the field. Introduction Purpose. As a result of the significant increase in multiple FDA approved therapeutic agents for use in patients with metastatic castration-resistant prostate cancer, clinicians are challenged with a multitude of treatment options and potential sequencing agents that, consequently, make clinical decision-making more complex. These Guidelines were developed to provide a rational basis for treatment of patients with CRPC, based on currently available published data. The CRPC guideline was amended in 2014 to incorporate newly published literature specifically related to the use of radium-223 for the treatment of men with mCRPC. To assist in decision-making, six index patients were developed representing the most common scenarios that are encountered in clinical practice. These index patients were created based on the presence or absence of metastatic disease, the degree of symptoms, the patients’ performance status (defined by the ECOG scale) and the prior treatment with docetaxel-based chemotherapy. 1. Asymptomatic non-metastatic CRPC 2. Asymptomatic or minimally-symptomatic mCRPC without prior docetaxel chemotherapy 3. Symptomatic mCRPC, good performance status, no prior docetaxel chemotherapy 4. Symptomatic mCRPC, poor performance status, no prior docetaxel chemotherapy 5. Symptomatic mCRPC, good performance status, prior docetaxel chemotherapy 6. Symptomatic mCRPC, poor performance status, prior docetaxel chemotherapy The newly incorporated literature specifically relates to Index Patients 3, 4 and 5. A summary of the statements relating to all Index Patients can be found in the figure. Summary flowchart Since this is a rapidly evolving field, this guideline should be used in conjunction with recent systematic literature reviews and an understanding of the individual patient’s treatment goals. In all cases, the patient’s preferences and personal goals should be considered when choosing therapy. Although we are discussing castration-resistant disease, we support the standard of care to maintain castrate testosterone levels even in the face of castration-resistant disease. Methodology Consistent with the AUA published guideline methodology framework,1 the initial guideline development began with a comprehensive systematic review. The AUA commissioned an independent group to conduct a systematic review and meta-analysis of the published literature on various therapies for CRPC. The evidence report was limited to English-language, peer reviewed literature published between January 1996 and February 2013. Controlled vocabulary supplemented with keywords was used to search for the relevant concepts of prostate cancer and castration resistance. An expert panel identified additional references to supplement the electronic search, which were required to meet the same criteria as the previously used studies. The search strategy focused on commonly used as well as experimental therapies including systemic chemotherapy (estramustine, mitoxantrone, docetaxel, cabazitaxel), immunotherapy (sipuleucel-T) and vaccine therapy, agents targeting the androgen signaling pathway (abiraterone, ketoconazole, corticosteroids, antiandrogens), radiotherapy and radiopharmaceuticals (strontium-89 [Metastron®], Samarium- 153 [Quadramet®]), antiandrogen withdrawal, bone targeted therapies (zoledronic acid, denosumab), enzalutamide [androgen receptor inhibitor], palliative care and experimental therapy, (TAK700 [CYP-17 inhibitor], cabozantanib [cMET/VEGFR inhibitor], radium-223 [Alpharadin®]). The methodology team independently rated the methodological quality of the studies and provided an overall judgment of the body of evidence based on confidence in the available estimates of effect. This initial review included 303 eligible studies that addressed the pre-identified questions of interest. A large body of evidence evaluated established chemotherapy agents such as docetaxel [19 Randomized controlled trials (RCTs)], estramustine (5 RCTs) and mitoxantrone (5 RCTs). Randomized evidence was also available for various immunotherapies (8 RCTs), therapies targeting the androgen signaling pathway (12 RCTs), radiotherapy and radiopharmaceuticals (4 RCTs) and bone targeting therapies (6 RCTs). The quality of these trials was acceptable overall and ranged from moderate to low risk of bias. All remaining studies were otherwise non-randomized (observational) and considered to be at high risk of bias. The quality of the evidence (confidence in the estimates) was limited in many studies by indirectness. Indirectness occurs when studies use surrogate endpoints that depend on laboratory or radiographic measurements (PSA-free survival, PSA decline or PFS based on imaging).2 These outcomes usually are surrogates for other important outcomes more essential for decision making, such as mortality, pain and quality of life (QoL). Imprecision (wide confidence intervals due to small number of events) was also common in most CRPC trials and can lower the confidence in the provided estimates. In April 2014 the CRPC guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines in an effort to maintain currency. The amendment allowed for the incorporation of additional literature released since the initial publication of this guideline in 2013. A comprehensive search of several databases from February 2013 to February 2014, English language, was conducted. The search strategy was designed and conducted by an experienced librarian with input from the study’s principle investigator. Controlled vocabulary supplemented with keywords was used to search for studies on therapy for CRPC. The search yielded 998 references, of which 662 were excluded after duplicate abstract and title review. We retrieved the full texts for the 336 included studies. Eventually, 37 studies provided relevant data on the specific treatment modalities for CRPC. The resulting amendment focuses on the incorporation of literature relevant to the use of radium-223 in the treatment of men with mCRPC. The newly incorporated statements specifically relate to treatment of Index Patients 3, 4 and 5. Limitations of the Literature The initial systematic review and subsequent amendment process identified clear gaps in the available evidence base. None of the therapies identified in these reviews was curative or resulted in long-term remission. Therefore, primary research on new agents is clearly needed for this important and common condition. Future trials should also use and incorporate patient reported outcomes, such as QoL and pain control. For a complete discussion of the methodology and evidence grading, please refer to the unabridged guideline available at www.AUAnet.org/education/guidelines/castration-resistant-prostate-cancer.cfm. Background Definition For the purpose of the guideline, CRPC was defined as a rising PSA level and/or radiographic evidence of prostate cancer progression despite medical or surgical castration. Incidence and Epidemiology Prostate cancer is the most commonly diagnosed solid organ malignancy in the United States and remains the second leading cause of cancer deaths among American men. Approximately 240,000 new diagnoses of prostate cancer and over 28,000 deaths were estimated in the U.S. in 2012.3 Prostate cancer deaths are typically the result of mCRPC, and historically the median survival for men with mCRPC has been less than two years. The recent availability of novel treatments for mCRPC has given a resurgence of hope for these men as studies now demonstrate improved survival with a variety of new agents. However, the unfortunate reality is that mCRPC remains an incurable disease, and it is against this backdrop that we look to the future with cautious optimism and new hope for scientific discovery. The exact mechanism of transition from castration-sensitive prostate cancer to castration-resistant disease is still not fully understood, but with recent scientific breakthroughs in basic research, there is now a greater understanding. We now know that despite castrate levels of androgens, the androgen receptor remains active and continues to drive prostate cancer progression.4,5 This understanding has led to the development of novel agents aimed at further decreasing androgen production or blocking AR function. However, there are also many other biologic pathways that function independent of androgen signaling resulting in CRPC. The treatment of men with mCRPC has dramatically changed over the past decade. Prior to 2004, once patients failed primary androgen deprivation, treatments were administered solely for palliation. Landmark articles by Tannock et al6 and Petrylak et al7 demonstrated that docetaxel improved survival for these patients. Since the approval of docetaxel, five additional agents that show a survival benefit have been FDA-approved on the basis of randomized clinical trials. These have included enzalutamide and abiraterone, two agents designed specifically to affect the androgen axis;8,9 sipuleucel-T, which stimulates the immune system;10 cabazitaxel, a chemotherapeutic agent;11 and radium-223, a radionuclide therapy.12 These agents have been tested in multiple “disease states” of CRPC to determine if or when patients might benefit from each treatment. Other treatments for men with mCRPC have been shown to improve outcomes, but remain to be FDA approved.13 Guideline Amendments Index Patient 1: Asymptomatic Non-metastatic CRPC The initial clinical presentation of CRPC occurs in a patient with a rising PSA despite castration. This is typically defined as a patient with a rising PSA and no radiologic evidence of metastatic prostate cancer. The Prostate Cancer Clinical Trials Working Group 2 defines PSA only failure as a rising PSA that is greater than 2 ng/mL higher than the nadir; the rise has to be at least 25% over nadir and the rise has to be confirmed by a second PSA at least three weeks later. In addition, the patient is required to have castrate levels of testosterone (less than 50 ng/mL) and no radiographic evidence of metastatic disease.14 To date, there are no randomized trials showing an OS benefit in this patient population from a particular form of treatment. The 2014 amendment literature search did not uncover additional information relevant to this index patient; as such, Guideline Statements 1 to 3 related to Index Patient 1 remain unchanged. Index Patient 2: Asymptomatic or Minimally Symptomatic, mCRPC without Prior Docetaxel Chemotherapy This patient represents a common clinical presentation, and is characterized as having a rising PSA in the setting of castrate levels of testosterone, documented metastatic disease on radiographic imaging and no prior treatment with docetaxel chemotherapy. The key distinction between this patient and Index Patients 3 and 4 is symptom status. Specifically, this patient is defined as having no symptoms or mild symptoms attributable to his prostate cancer. However, one must then consider whether the patient requires regular opioid pain medications for symptoms thought to be attributable to documented metastases to achieve this level of pain control. In general, if patients require regular narcotic medications for pain relief, they are not included in this category. The 2014 amendment literature search did not uncover additional information relevant to this index patient; as such, Guideline Statements 4 and 5 related to Index Patient 2 remain unchanged. Index Patient 3: Symptomatic, mCRPC with Good Performance Status and no Prior Docetaxel Chemotherapy These patients have a rising PSA in the setting of castrate levels of testosterone, documented symptomatic metastatic disease on radiographic imaging and no prior history of docetaxel chemotherapy. The definition of symptomatic disease warrants additional explanation to contrast with Index Patient 2. First, the patient must have symptoms that are clearly attributable to the metastatic disease burden, not any other medical condition. Second, if having pain, the patient should require regular opiate pain medications for symptoms attributable to documented metastases in order to achieve an acceptable level of pain control. If patients require regular narcotic medications for pain relief, then they are symptomatic from their prostate cancer and should be included in this category. Additional information published since the 2013 release of this guideline related to the use of radium-223 in the treatment of CRPC warranted the addition of Guideline Statement 9. All other statements relevant to Index Patient 3 (Guideline Statements 6 to 8, 10) remain unchanged. Guideline Statement 9 Clinicians should offer radium-223 to patients with symptomatic, mCRPC with good performance status and no prior docetaxel chemotherapy with symptomatic bone metastases and without known visceral disease. (Standard; Evidence Strength: Grade B) Radium-223 is an α-emitting radiopharmaceutical capable of inducing double strand DNA breaks in cancer cells while minimizing exposure to surrounding marrow. The use of radium-223 for the treatment on bone metastases relies on the chemical similarity to calcium and the ability of the α-radiation and the short-lived decay products of radium-223 to kill cancer cells. The short range of α-radiation reduces the damage to surrounding healthy tissue creating a more localized effect compared to other radionuclide therapies, such as strontium-89. This is an appropriate treatment for patients with symptomatic bone pain and non-visceral metastases. A phase III trial with radium-223 in symptomatic men with progressive mCRPC with or without prior docetaxel exposure and no evidence of visceral metastasis reported improvement in median survival (14.9 months vs 11.3 months, HR 0.695, 95% CI 0.581–0.832, p=0.00007) in favor of radium-223 over placebo. Time to first skeleton related event improved from 9.8 month with placebo to 15.6 months with radium-223 (HR 0.658, 95% CI 0.522–0.830, p=0.00037). Significant improvements in QoL measurements were reported in the patients treated with radium-223. Of the 921 patients of this trial, those receiving treatment were given six intravenous injections with a dose of 50 kBq per kilogram of body weight every four weeks.12 Rates of grade 3 or 4 neutropenia and thrombocytopenia were low at 2.2% and 6.3%, respectively.15 Index Patient 4: Symptomatic, mCRPC with Poor Performance Status and no Prior Docetaxel Chemotherapy Clinical trials have generally excluded patients with a poor performance status (ECOG 3-4) from participation. Thus, most data regarding management of patients is extrapolated from randomized trials of eligible patients who had a better performance status. Even a phase III clinical trial that was presumptively designed for a population considered “unfit” for docetaxel (ALSYMPCA to evaluate radium-223) still only allowed a performance status of ECOG 0-1. However, treatments with acceptable safety profiles do exist and should be considered, even in poor performance status patients. This is especially true in those patients in whom the poor performance status is directly related to the cancer itself and thus whose status might improve with treatment. Additional information published since the 2013 release of this guideline related to the use of radium-223 in the treatment of CRPC warranted the addition of Guideline Statement 14. All other statements relevant to Index Patient 4 (Guideline Statements 11 to 13, 15) remain unchanged. Guideline Statement 14 Clinicians may offer radium-223 to patients with symptomatic mCRPC with poor performance status and no prior docetaxel chemotherapy with symptomatic bone metastases and without known visceral disease in select cases, specifically when the performance status is directly related to symptoms related to bone metastases. (Expert Opinion) Radium-223 may be offered for patients with symptomatic bone pain and non-visceral metastases. Radium-223 has showed survival benefit in patients with good performance status. If it is believed that the poor performance status of Index Patient 4 is due to symptomatic bone pain, radium-223 may also be beneficial to these patients. Samarium-153 and strontium-89 have not shown a survival benefit but may offer palliative benefit in patients symptomatic with bone pain. These are further discussed under Index Patient 6. Index Patient 5: Symptomatic, mCRPC with Good Performance Status and Prior Docetaxel Chemotherapy As patients with prostate cancer receive hormonal therapy earlier in the course of the disease (frequently for non-metastatic disease), they may actually develop castration-resistant disease (based on serologic progression) with non-metastatic or asymptomatic metastatic disease. Thus, additional agents, including docetaxel chemotherapy may be administered earlier in the course of metastatic disease. These trends have resulted in a population of mCRPC patients who have completed docetaxel and may continue to be asymptomatic or minimally-symptomatic with an excellent performance status. While such patients may be healthy enough to receive a number of subsequent therapies, a focus of therapy should also be to maintain their excellent performance status without significant toxicity from additional therapy. It is in this context that providers should choose from a number of additional therapies to offer to this patient population. Additional information published since the 2013 release of this guideline related to the use of radium-223 in the treatment of CRPC warranted the addition of Guideline Statement 19. All other statements relevant to Index Patient 5 (Guideline Statements 16 to 18) remain unchanged. Guideline Statement 19 Clinicians should offer radium-223 to patients with good performance status who received prior docetaxel chemotherapy with symptomatic bone metastases and without known visceral disease. (Standard; (Evidence Strength: Grade B) During the course of cancer treatment, bone marrow can become infiltrated by the cancer. Chemotherapeutic agents, such as docetaxel, can suppress bone marrow function while being used to extend survival and improve QoL. Radium-223 was shown to be an effective therapy in the previously discussed Parker et al. study12 in which 57% of patients had previously received chemotherapy. As with other treatments, such as electron beam radiation therapy, side effects can include anemia and thrombocytopenia. Those patients who have previously received chemotherapy are at greater risk for such side effects compared to chemotherapy naïve patients. Index Patient 6: Symptomatic, mCRPC with Poor Performance Status and Prior Docetaxel Chemotherapy The American Society of Clinical Oncology has posted recommendations regarding treatment for patients with advanced solid tumors; particularly in the last months of life. The society advocates for an increasing emphasis on a patient’s QoL and concentrates on symptom management. Treatment given in the last months of life may delay access to end of life care, increase costs and add unnecessary symptom management. Patients with poor performance status (ECOG 3 or 4) should not be offered further treatment (https://connection.asco.org/Magazine/Article/ID/3190/Choosing-Wisely-Constructing-a-Top-Five-List-in-Oncology.aspx). Additional information published since the 2013 release of this guideline related to the use of radium-223 in the treatment of CRPC warranted the addition of discussion text to Guideline Statement 20; however, the statement itself as well as Guideline Statement 21 remains unchanged from the initial 2013 release of this guideline. Guideline Statement 20 Clinicians should offer palliative care to patients with mCRPC with poor performance status who received prior docetaxel chemotherapy. Alternatively, for selected patients, clinicians may offer treatment with abiraterone + prednisone, enzalutamide, ketoconazole + steroid or radionuclide therapy. (Expert Opinion) Palliative care is an interdisciplinary, holistic approach to managing an advanced disease such as cancer with a guarded prognosis. It can include controlling symptoms that are physical, psychological, spiritual and social. The goal of palliation is to prevent and relieve suffering and to support the best possible QoL for the patient and family. Advanced prostate cancer can be debilitating with bone pain, fatigue and weight loss. Palliative radiotherapy can be an option for controlling bone pain in some patients. An increasing dependence upon others and a feeling of losing control can contribute to anxiety and depression. Other symptoms include urinary outflow obstruction, weakness secondary to spinal cord compression, lymphedema and anemia. Evaluation and treatment should be comprehensive and patient centered, focusing on the goals of the individual patient as well as the patient’s family. Comprehensive palliative care often requires a multidisciplinary approach where various providers of differing expertise assess and treat the complex needs of the advanced disease prostate cancer patient.16,17 Radionuclide Therapy One example of a Phase III randomized clinical trial of radioactive samarium-153 (153Sm) lexidronam versus nonradioactive 153Sm-lexidronam for palliation of bone pain in patients with CRPC is by Sartor.18 A total of 152 men with painful bone metastases were enrolled in this prospective, randomized, double-blind trial. Patients were randomized (2:1) to the radioactive 153Sm-lexidronam agent. Patients completed pain and analgesic diaries twice daily. Blinded medications were given intravenously; the study was unblinded after four weeks when 28 of 52 placebo patients had not achieved satisfactory pain relief by week four; 22 of 28 chose to receive open label treatment with radioactive 153Sm-lexidronam. The authors concluded that 1 mCi/kg 153Sm-lexidronam is safe and effective for palliation of painful bone metastases in patients with hormone-refractory prostate cancer. Side effects included mild bone marrow suppression. Multiple non-randomized trials have been done with samarium-153 alone19,20 with unclear adverse events and outcomes. Other studies included samarium-153 with docetaxel;21,22 these studies were also unclear in outcomes or adverse events. Studies looking at radium-223 have focused on those patients with good performance status, and there is no data indicating an advantage over standard radiopharmaceuticals in this patient population. Bone Health The 2014 amendment literature search did not uncover additional information relevant to bone health; as such, Guideline Statements 22 and 23 remain unchanged from the 2013 publication of this guideline. Future Directions Over the past 15 years there has been un-paralleled scientific progress and investment in drug development for patients with mCRPC. As a direct result of these studies, several lines of systemic therapies have been FDA approved for use in mCRPC on grounds of pain palliation, minimizing disease adverse effects and prolonging survival. Ongoing Research In addition to agents discussed above, several other drugs are in the pipeline. Completed, Unpublished Phase III Trial as of Guideline Publication Enzalutamide: The Phase III PREVAIL trial evaluating enzalutamide versus placebo in chemotherapy-naive men with mCRPC was stopped early by the Data Safety Monitoring Committee after an interim analysis revealed improvements in overall survival (HR 0.706, 95% CI 0.60–0.84) and radiographic progression-free survival (HR 0.186, 95% CI 0.15–0.23) for the enzalutamide arm. A total of 1,717 men with asymptomatic or mildly symptomatic mCRPC (including some with visceral metastases) were randomly assigned to placebo versus 160 mg/day of enzalutamide.23 These data were recently published on June 1, 2014. As final publication occurred after the release of this guideline amendment, this publication will be incorporated into future updates of this guideline. Ongoing Phase III Trials as of Guideline Publication Orteronel Orteronel is a CYP17A inhibitor but is more specifically a 17,20-lyase inhibitor. As of the publication of this amendment, this drug was being tested in a phase III trial comparing orteronel and prednisone to placebo and prednisone (NCT01193244). As of June 19, 2014, following the publication of this amendment, the development program for orteronel was voluntarily terminated following Phase III results that showed that the drug failed to extend patient OS. Tasquinomod Tasquinomod is an orally active quinoline-3-carboxamide. It has anti-angiogenic and anti-tumor properties and is currently in ongoing phase III testing to assess men with bone-metastatic disease to assess its impact on survival (NCT01234311). Immunotherapy Novel vaccine strategies to harness the immune system are being tested, such as PROSTVAC in asymptomatic, chemotherapy-naïve men with mCRPC in a phase III study randomizing participants to PROSTVAC with or without GM-CSF or to placebo (NCT01322490). Other immune based strategies include inhibition of immune check points using Ipilimumab, which is a monoclonal anti-CTLA4 antibody that binds to the CTLA-4 receptor on T cells, blocking CTLA4 and, in turn, activating T-cell anti-tumor activity. A phase III study comparing ipilimumab to placebo is ongoing (NCT01057810). Custirsen Custirsen inhibits the production of clusterin, a protein associated with treatment resistance in a number of cancers, including prostate cancer. Adding agents with novel or different mechanisms of action to a docetaxel-backbone remains an area of s" @default.
• W2125146007 created "2016-06-24" @default.
• W2125146007 creator A5040850986 @default.
• W2125146007 creator A5050663947 @default.
• W2125146007 creator A5054802858 @default.
• W2125146007 creator A5056866163 @default.
• W2125146007 creator A5082394596 @default.
• W2125146007 date "2015-02-01" @default.
• W2125146007 modified "2023-10-05" @default.
• W2125146007 title "Castration-Resistant Prostate Cancer: AUA Guideline Amendment" @default.
• W2125146007 cites W1247968195 @default.
• W2125146007 cites W2007745674 @default.
• W2125146007 cites W2009344268 @default.
• W2125146007 cites W2056788444 @default.
• W2125146007 cites W2079832124 @default.
• W2125146007 cites W2080439368 @default.
• W2125146007 cites W2098537321 @default.
• W2125146007 cites W2103959341 @default.
• W2125146007 cites W2110534364 @default.
• W2125146007 cites W2110707581 @default.
• W2125146007 cites W2120292596 @default.
• W2125146007 cites W2123526148 @default.
• W2125146007 cites W2141454098 @default.
• W2125146007 cites W2141569270 @default.
• W2125146007 cites W2148643283 @default.
• W2125146007 cites W2149547695 @default.
• W2125146007 cites W2150919715 @default.
• W2125146007 cites W2158011521 @default.
• W2125146007 cites W2165948908 @default.
• W2125146007 cites W2166918329 @default.
• W2125146007 cites W2167331614 @default.
• W2125146007 cites W3000564989 @default.
• W2125146007 doi "https://doi.org/10.1016/j.juro.2014.10.104" @default.
• W2125146007 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30086276" @default.
• W2125146007 hasPublicationYear "2015" @default.
• W2125146007 type Work @default.
• W2125146007 sameAs 2125146007 @default.
• W2125146007 citedByCount "135" @default.
• W2125146007 countsByYear W21251460072015 @default.
• W2125146007 countsByYear W21251460072016 @default.
• W2125146007 countsByYear W21251460072017 @default.
• W2125146007 countsByYear W21251460072018 @default.
• W2125146007 countsByYear W21251460072019 @default.
• W2125146007 countsByYear W21251460072020 @default.
• W2125146007 countsByYear W21251460072021 @default.
• W2125146007 countsByYear W21251460072022 @default.
• W2125146007 countsByYear W21251460072023 @default.
• W2125146007 crossrefType "journal-article" @default.
• W2125146007 hasAuthorship W2125146007A5040850986 @default.
• W2125146007 hasAuthorship W2125146007A5050663947 @default.
• W2125146007 hasAuthorship W2125146007A5054802858 @default.
• W2125146007 hasAuthorship W2125146007A5056866163 @default.
• W2125146007 hasAuthorship W2125146007A5082394596 @default.
• W2125146007 hasConcept C121608353 @default.
• W2125146007 hasConcept C126322002 @default.
• W2125146007 hasConcept C142724271 @default.
• W2125146007 hasConcept C143998085 @default.
• W2125146007 hasConcept C2776235491 @default.
• W2125146007 hasConcept C2780182762 @default.
• W2125146007 hasConcept C2780192828 @default.
• W2125146007 hasConcept C29456083 @default.
• W2125146007 hasConcept C71924100 @default.
• W2125146007 hasConceptScore W2125146007C121608353 @default.
• W2125146007 hasConceptScore W2125146007C126322002 @default.
• W2125146007 hasConceptScore W2125146007C142724271 @default.
• W2125146007 hasConceptScore W2125146007C143998085 @default.
• W2125146007 hasConceptScore W2125146007C2776235491 @default.
• W2125146007 hasConceptScore W2125146007C2780182762 @default.
• W2125146007 hasConceptScore W2125146007C2780192828 @default.
• W2125146007 hasConceptScore W2125146007C29456083 @default.
• W2125146007 hasConceptScore W2125146007C71924100 @default.
• W2125146007 hasIssue "2" @default.
• W2125146007 hasLocation W21251460071 @default.
• W2125146007 hasLocation W21251460072 @default.
• W2125146007 hasOpenAccess W2125146007 @default.
• W2125146007 hasPrimaryLocation W21251460071 @default.
• W2125146007 hasRelatedWork W1497253641 @default.
• W2125146007 hasRelatedWork W1980245127 @default.
• W2125146007 hasRelatedWork W2060381175 @default.
• W2125146007 hasRelatedWork W2075763133 @default.
• W2125146007 hasRelatedWork W2088520467 @default.
• W2125146007 hasRelatedWork W2376423713 @default.
• W2125146007 hasRelatedWork W2386364393 @default.
• W2125146007 hasRelatedWork W2400504790 @default.
• W2125146007 hasRelatedWork W3032731309 @default.
• W2125146007 hasRelatedWork W4249487090 @default.
• W2125146007 hasVolume "193" @default.
• W2125146007 isParatext "false" @default.
• W2125146007 isRetracted "false" @default.
• W2125146007 magId "2125146007" @default.
• W2125146007 workType "article" @default.