Phase I study of procaspase-activating compound-1 (PAC-1) in the treatment of advanced malignancies.

BACKGROUND: Procaspase-3 (PC-3) is overexpressed in multiple tumour types and procaspase-activating compound 1 (PAC-1) directly activates PC-3 and induces apoptosis in cancer cells. This report describes the first-in-human, phase I study of PAC-1 assessing maximum tolerated dose, safety, and pharmacokinetics. METHODS: Modified-Fibonacci dose-escalation 3 + 3 design was used. PAC-1 was administered orally at 7 dose levels (DL) on days 1-21 of a 28-day cycle. Dose-limiting toxicity (DLT) was assessed during the first two cycles of therapy, and pharmacokinetics analysis was conducted on days 1 and 21 of the first cycle. Neurologic and neurocognitive function (NNCF) tests were performed throughout the study. RESULTS: Forty-eight patients were enrolled with 33 completing ≥2 cycles of therapy and evaluable for DLT. DL 7 (750 mg/day) was established as the recommended phase 2 dose, with grade 1 and 2 neurological adverse events noted, while NNCF testing showed stable neurologic and cognitive evaluations. PAC-1's t1/2 was 28.5 h after multi-dosing, and systemic drug exposures achieved predicted therapeutic concentrations. PAC-1 clinical activity was observed in patients with neuroendocrine tumour (NET) with 2/5 patients achieving durable partial response. CONCLUSIONS: PAC-1 dose at 750 mg/day was recommended for phase 2 studies. Activity of PAC-1 in treatment-refractory NET warrants further investigation. CLINICAL TRIAL REGISTRATION: Clinical Trials.gov: NCT02355535.

Racial Disparities in COVID-19 Outcomes Among Black and White Patients With Cancer.

Importance: Non-Hispanic Black individuals experience a higher burden of COVID-19 than the general population; hence, there is an urgent need to characterize the unique clinical course and outcomes of COVID-19 in Black patients with cancer. Objective: To investigate racial disparities in severity of COVID-19 presentation, clinical complications, and outcomes between Black patients and non-Hispanic White patients with cancer and COVID-19. Design, Setting, and Participants: This retrospective cohort study used data from the COVID-19 and Cancer Consortium registry from March 17, 2020, to November 18, 2020, to examine the clinical characteristics and outcomes of COVID-19 in Black patients with cancer. Data analysis was performed from December 2020 to February 2021. Exposures: Black and White race recorded in patient's electronic health record. Main Outcomes and Measures: An a priori 5-level ordinal scale including hospitalization intensive care unit admission, mechanical ventilation, and all-cause death. Results: Among 3506 included patients (1768 women [50%]; median [IQR] age, 67 [58-77] years), 1068 (30%) were Black and 2438 (70%) were White. Black patients had higher rates of preexisting comorbidities compared with White patients, including obesity (480 Black patients [45%] vs 925 White patients [38%]), diabetes (411 Black patients [38%] vs 574 White patients [24%]), and kidney disease (248 Black patients [23%] vs 392 White patients [16%]). Despite the similar distribution of cancer type, cancer status, and anticancer therapy at the time of COVID-19 diagnosis, Black patients presented with worse illness and had significantly worse COVID-19 severity (unweighted odds ratio, 1.34 [95% CI, 1.15-1.58]; weighted odds ratio, 1.21 [95% CI, 1.11-1.33]). Conclusions and Relevance: These findings suggest that Black patients with cancer experience worse COVID-19 outcomes compared with White patients. Understanding and addressing racial inequities within the causal framework of structural racism is essential to reduce the disproportionate burden of diseases, such as COVID-19 and cancer, in Black patients.

Chasm Between Cancer Quality Measures and Electronic Health Record Data Quality.

PURPOSE: The Medicare Access and CHIP Reauthorization Act of 2015 (MACRA) requires eligible clinicians to report clinical quality measures (CQMs) in the Merit-Based Incentive Payment System (MIPS) to maximize reimbursement. To determine whether structured data in electronic health records (EHRs) were adequate to report MIPS CQMs, EHR data aggregated by ASCO's CancerLinQ platform were analyzed. MATERIALS AND METHODS: Using the CancerLinQ health technology platform, 19 Oncology MIPS (oMIPS) CQMs were evaluated to determine the presence of data elements (DEs) necessary to satisfy each CQM and the DE percent population with patient data (fill rates). At the time of this analysis, the CancerLinQ network comprised 63 active practices, representing eight different EHR vendors and containing records for more than 1.63 million unique patients with one or more malignant neoplasms (1.73 million cancer cases). RESULTS: Fill rates for the 63 oMIPS-associated DEs varied widely among the practices. The average site had at least one filled DE for 52% of the DEs. Only 35% of the DEs were populated for at least one patient record in 95% of the practices. However, the average DE fill rate of all practices was 23%. No data were found at any practice for 22% of the DEs. Since any oMIPS CQM with an unpopulated DE component resulted in an inability to compute the measure, only two (10.5%) of the 19 oMIPS CQMs were computable for more than 1% of the patients. CONCLUSION: Although EHR systems had relatively high DE fill rates for some DEs, underfilling and inconsistency of DEs in EHRs render automated oncology MIPS CQM calculations impractical.

Assessment of Regional Variability in COVID-19 Outcomes Among Patients With Cancer in the United States.

Importance: The COVID-19 pandemic has had a distinct spatiotemporal pattern in the United States. Patients with cancer are at higher risk of severe complications from COVID-19, but it is not well known whether COVID-19 outcomes in this patient population were associated with geography. Objective: To quantify spatiotemporal variation in COVID-19 outcomes among patients with cancer. Design, Setting, and Participants: This registry-based retrospective cohort study included patients with a historical diagnosis of invasive malignant neoplasm and laboratory-confirmed SARS-CoV-2 infection between March and November 2020. Data were collected from cancer care delivery centers in the United States. Exposures: Patient residence was categorized into 9 US census divisions. Cancer center characteristics included academic or community classification, rural-urban continuum code (RUCC), and social vulnerability index. Main Outcomes and Measures: The primary outcome was 30-day all-cause mortality. The secondary composite outcome consisted of receipt of mechanical ventilation, intensive care unit admission, and all-cause death. Multilevel mixed-effects models estimated associations of center-level and census division-level exposures with outcomes after adjustment for patient-level risk factors and quantified variation in adjusted outcomes across centers, census divisions, and calendar time. Results: Data for 4749 patients (median [IQR] age, 66 [56-76] years; 2439 [51.4%] female individuals, 1079 [22.7%] non-Hispanic Black individuals, and 690 [14.5%] Hispanic individuals) were reported from 83 centers in the Northeast (1564 patients [32.9%]), Midwest (1638 [34.5%]), South (894 [18.8%]), and West (653 [13.8%]). After adjustment for patient characteristics, including month of COVID-19 diagnosis, estimated 30-day mortality rates ranged from 5.2% to 26.6% across centers. Patients from centers located in metropolitan areas with population less than 250 000 (RUCC 3) had lower odds of 30-day mortality compared with patients from centers in metropolitan areas with population at least 1 million (RUCC 1) (adjusted odds ratio [aOR], 0.31; 95% CI, 0.11-0.84). The type of center was not significantly associated with primary or secondary outcomes. There were no statistically significant differences in outcome rates across the 9 census divisions, but adjusted mortality rates significantly improved over time (eg, September to November vs March to May: aOR, 0.32; 95% CI, 0.17-0.58). Conclusions and Relevance: In this registry-based cohort study, significant differences in COVID-19 outcomes across US census divisions were not observed. However, substantial heterogeneity in COVID-19 outcomes across cancer care delivery centers was found. Attention to implementing standardized guidelines for the care of patients with cancer and COVID-19 could improve outcomes for these vulnerable patients.

External Beam Radiation Therapy for Primary Liver Cancers: An ASTRO Clinical Practice Guideline.

PURPOSE: This guideline provides evidence-based recommendations for the indications and technique-dose of external beam radiation therapy (EBRT) in hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (IHC). METHODS: The American Society for Radiation Oncology convened a task force to address 5 key questions focused on the indications, techniques, and outcomes of EBRT in HCC and IHC. This guideline is intended to cover the definitive, consolidative, salvage, preoperative (including bridge to transplant), and adjuvant settings as well as palliative EBRT for symptomatic primary lesions. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS: Strong recommendations are made for using EBRT as a potential first-line treatment in patients with liver-confined HCC who are not candidates for curative therapy, as consolidative therapy after incomplete response to liver-directed therapies, and as a salvage option for local recurrences. The guideline conditionally recommends EBRT for patients with liver-confined multifocal or unresectable HCC or those with macrovascular invasion, sequenced with systemic or catheter-based therapies. Palliative EBRT is conditionally recommended for symptomatic primary HCC and/or macrovascular tumor thrombi. EBRT is conditionally recommended as a bridge to transplant or before surgery in carefully selected patients. For patients with unresectable IHC, consolidative EBRT with or without chemotherapy should be considered, typically after systemic therapy. Adjuvant EBRT is conditionally recommended for resected IHC with high-risk features. Selection of dose-fractionation regimen and technique should be based on disease extent, disease location, underlying liver function, and available technologies. CONCLUSIONS: The task force has proposed recommendations to inform best clinical practices on the use of EBRT for HCC and IHC with strong emphasis on multidisciplinary care. Future studies should focus on further defining the role of EBRT in the context of liver-directed and systemic therapies and refining optimal regimens and techniques.

Chemotherapy Knowledge Base Management in the Era of Precision Oncology.

Cancer medicine has grown increasingly complex in recent years with the advent of precision oncology and wide utilization of multidrug regimens. Representing this increasingly granular knowledge is a significant challenge. As users and managers of a freely available chemotherapy drug and regimen database, we describe the changes we have made to accommodate these challenges. These include the development of a domain ontology and increased granularity in the classification of cancer types on the website.

Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline.

PURPOSE: To develop an evidence-based clinical practice guideline to assist in clinical decision making for patients with advanced hepatocellular carcinoma (HCC). METHODS: ASCO convened an Expert Panel to conduct a systematic review of published phase III randomized controlled trials (2007-2020) on systemic therapy for advanced HCC and provide recommended care options for this patient population. RESULTS: Nine phase III randomized controlled trials met the inclusion criteria. RECOMMENDATIONS: Atezolizumab + bevacizumab (atezo + bev) may be offered as first-line treatment of most patients with advanced HCC, Child-Pugh class A liver disease, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-1, and following management of esophageal varices, when present, according to institutional guidelines. Where there are contraindications to atezolizumab and/or bevacizumab, tyrosine kinase inhibitors sorafenib or lenvatinib may be offered as first-line treatment of patients with advanced HCC, Child-Pugh class A liver disease, and ECOG PS 0-1. Following first-line treatment with atezo + bev, and until better data are available, second-line therapy with a tyrosine kinase inhibitor may be recommended for appropriate candidates. Following first-line therapy with sorafenib or lenvatinib, second-line therapy options for appropriate candidates include cabozantinib, regorafenib for patients who previously tolerated sorafenib, or ramucirumab (for patients with α-fetoprotein ≥ 400 ng/mL), or atezo + bev where patients did not have access to this option as first-line therapy. Pembrolizumab or nivolumab are also reasonable options for appropriate patients following sorafenib or lenvatinib. Consideration of nivolumab + ipilimumab as an option for second-line therapy and third-line therapy is discussed. Further guidance on choosing between therapy options is included within the guideline. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines.

Seven decades of chemotherapy clinical trials: a pan-cancer social network analysis.

Clinical trials establish the standard of cancer care, yet the evolution and characteristics of the social dynamics between the people conducting this work remain understudied. We performed a social network analysis of authors publishing chemotherapy-based prospective trials from 1946 to 2018 to understand how social influences, including the role of gender, have influenced the growth and development of this network, which has expanded exponentially from fewer than 50 authors in 1946 to 29,197 in 2018. While 99.4% of authors were directly or indirectly connected by 2018, our results indicate a tendency to predominantly connect with others in the same or similar fields, as well as an increasing disparity in author impact and number of connections. Scale-free effects were evident, with small numbers of individuals having disproportionate impact. Women were under-represented and likelier to have lower impact, shorter productive periods (P < 0.001 for both comparisons), less centrality, and a greater proportion of co-authors in their same subspecialty. The past 30 years were characterized by a trend towards increased authorship by women, with new author parity anticipated in 2032. The network of cancer clinical trialists is best characterized as strategic or mixed-motive, with cooperative and competitive elements influencing its appearance. Network effects such as low centrality, which may limit access to high-profile individuals, likely contribute to the observed disparities.

Phase I Study of IGF-Methotrexate Conjugate in the Treatment of Advanced Tumors Expressing IGF-1R.

OBJECTIVES: Insulin-like growth factor-methotrexate (IGF-MTX) is a conjugate of methotrexate and 765IGF, a variant of IGF-1 with high affinity for insulin-like growth factor type 1 receptor. The study aim was to determine the maximum tolerated dose of IGF-MTX in refractory solid organ and hematologic malignancies expressing insulin-like growth factor type 1 receptor. MATERIALS AND METHODS: This phase I trial used a modified toxicity probability interval design with 5 cohort dose levels, and expansion cohort at maximum tolerated dose. IGF-MTX was given intravenously over 90 minutes on days 1, 8, and 15 of a 28-day cycle. RESULTS: A total of 17 patients were enrolled. The highest tolerated dose tested was 0.80 µEq/kg with dose-limiting toxicity of grade 3 hypoglycemia. Drug-related grade 3 and 4 toxicities included abdominal pain (26%), hypoglycemia (10%), and hypotension (10%). Of the 15 evaluable for response, 3 patients (20%) had stable disease, including the patient with Hodgkin lymphoma with stable disease for 12 cycles of therapy. IGF-MTX concentrations declined rapidly, with half-lives of 5.2 to 14 minutes for the initial distribution phase and 6.5 to 7.5 hours for the terminal elimination phase. Higher IGF-R1 expression did not correlate with better outcome. CONCLUSIONS: IGF-MTX is well tolerated. IGF-MTX pharmacokinetics suggest rapid cellular uptake. The activity of IGF-MTX in Hodgkin lymphoma should be explored.

The Spectrum of Pulmonary Toxicity in Pancreatic Cancer Patients Receiving Gemcitabine Combination Chemotherapy.

Gemcitabine is widely utilized in the treatment of pancreatic, ovarian, and non small cell lung cancers. Gemcitabine is associated with a wide spectrum of lung toxicities, ranging from dyspnea 25% of patients to severe pulmonary toxicity in up to 5% of patients. There is a dearth of information specific to pulmonary toxicity in the setting of gemcitabine combination chemotherapy. Given the potential severity, it is important to identify it early by excluding more common etiologies. We share two case reports of patients with pancreatic cancer who developed severe pulmonary toxicity during gemcitabine combination chemotherapy. Both cases emphasize the heightened risk of pulmonary toxicity in patients receiving gemcitabine chemotherapy combinations, and a need to be vigilant to initiate appropriate therapies immediately.

Phase I Study of Aurora A Kinase Inhibitor Alisertib (MLN8237) in Combination With Selective VEGFR Inhibitor Pazopanib for Therapy of Advanced Solid Tumors.

OBJECTIVES: Pazopanib is a multikinase angiogenesis inhibitor. Alisertib is a highly selective inhibitor of mitotic Aurora A kinase. There is preclinical evidence that mitosis-targeting agents exhibit antiangiogenic effects. Thus, the combination of these 2 agents may have a synergistic effect on tumor vasculature. The primary objective of this study is to determine the optimal tolerated dose (OTD) for alisertib and pazopanib. MATERIALS AND METHODS: This phase 1b study evaluated the OTD of alisertib twice a day, on days 1 to 7 with pazopanib, once a day, continuously in a 21-day cycle, both taken orally. Disease response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1 every 2 cycles. OTD cohort was expanded to assure safety and perform pharmacokinetics analysis. RESULTS: A total of 27 patients received treatment. Seventy-seven percent of the patients had received at least 3 prior chemotherapy regimens. Dose-limiting toxicities occurred in dose level (DL) 2+ (grade 4 thrombocytopenia and grade 3 mucositis) and DL 3 (grade 3 liver transaminases elevation and grade 3 abdominal pain). The OTD was determined to be DL 2: alisertib 20 mg twice daily and pazopanib 600 mg daily. Pharmacokinetic analysis revealed that clearance of alisertib was reduced by ∼40% in the presence of pazopanib compared with clearance in the absence of pazopanib. Fourteen patients had stable disease and 2 patients had a partial response. CONCLUSIONS: The combination of alisertib with pazopanib demonstrates manageable safety and early clinical evidence of antitumor activity in patients with advanced malignancies (NCT01639911).

Patient-centered design in developing a mobile application for oral anticancer medications.

OBJECTIVES: To develop and test the usability and feasibility of a customizable mobile application (app) designed to help educate patients about their oral anticancer medications (OAMs) and regimens. SETTING: Outpatient cancer center and oncology pharmacy for urban, Midwestern academic health system. PRACTICE DESCRIPTION: Clinically-supervised educational intervention to support patients learning about OAMs. PRACTICE INNOVATION: With input from patient partners, our interdisciplinary team designed the first known tablet-based educational app that can interface with a patient's electronic medical record. The app is based on learning style and adherence theories and is customizable for individually prescribed OAMs. The app can accommodate multiple learning styles through text at 6th-grade reading level, pictures, animations, and audio voiceovers. Functionalities include interactive educational modules on 11 OAMs and case-based patient stories on common barriers to OAM adherence. EVALUATION: Early phase testing provided the opportunity to observe the user interface with the app and app functionality. Data were summarized descriptively from observations and comments of patient subjects. RESULTS: Thirty patient subjects provided input-19 in phase 1 usability testing and 11 in phase 2 feasibility testing. Comments provided by patient subjects during usability testing were largely positive. Responses included self-identification with patient stories, usefulness of drug information, preferences for text messages, and app limitations (e.g., perceived generational digital divide in technology use and potential patient inability to receive text messages). Using their feedback, modifications were made to the prototype app. Responses in feasibility testing demonstrated the app's usefulness across a wide range of ages. Highest opinion ratings on app usefulness were stated by patients who were newer to OAM therapy. CONCLUSION: User feedback suggests the potential benefit of the app as a tool to help patients with cancer, particularly after the first months for those starting new OAM regimens. Processes and lessons learned are transferable to other settings.

A case report of paraneoplastic syndrome in ß-hCG-secreting duodenal adenocarcinoma.

Human chorionic gonadotropin (hCG) is a glycoprotein hormone that is used in clinical practice to detect pregnancy and serves as a sensitive marker for trophoblastic tumors. Other organs besides placental trophoblasts naturally express the hormone at low levels, which can be elevated in nontrophoblastic malignancies. Some studies have suggested that elevated ß-hCG levels in nontrophoblastic tumors are a sign of aggressive disease and strongly associated with poor prognosis. We describe a case of a 50-year-old post-menopausal woman with metastatic duodenal adenocarcinoma who presented with a negative pregnancy test that later changed to positive. Biopsy of the primary duodenal mass showed positive immunohistochemical expression of ß-hCG. The patient was also found to have multiple brain metastases, which is uncommon in gastrointestinal cancer. This is a rare case of paraneoplastic syndrome in a ß-hCG-secreting duodenal adenocarcinoma.

Adherence to Oral Anticancer Medications: Evolving Interprofessional Roles and Pharmacist Workforce Considerations.

Interprofessional care is exhibited in outpatient oncology practices where practitioners from a myriad of specialties (e.g., oncology, nursing, pharmacy, health informatics and others) work collectively with patients to enhance therapeutic outcomes and minimize adverse effects. Historically, most ambulatory-based anticancer medication therapies have been administrated in infusion clinics or physician offices. Oral anticancer medications (OAMs) have become increasingly prevalent and preferred by patients for use in residential or other non-clinic settings. Self-administration of OAMs represents a significant shift in the management of cancer care and role responsibilities for patients and clinicians. While patients have a greater sense of empowerment and convenience when taking OAMs, adherence is a greater challenge than with intravenous therapies. This paper proposes use of a qualitative systems evaluation, based on theoretical frameworks for interdisciplinary team collaboration and systems science, to examine the social interactionism involved with the use of intravenous anticancer treatments and OAMs (as treatment technologies) by describing patient, organizational, and social systems considerations in communication, care, control, and context (i.e., Kaplan's 4Cs). This conceptualization can help the healthcare system prepare for substantial workforce changes in cancer management, including increased utilization of oncology pharmacists.

Features of hepatocellular carcinoma in Hispanics differ from African Americans and non-Hispanic Whites.

AIM: To compare features of hepatocellular carcinoma (HCC) in Hispanics to those of African Americans and Whites. METHODS: Patients treated for HCC at an urban tertiary medical center from 2005 to 2011 were identified from a tumor registry. Data were collected retrospectively, including demographics, comorbidities, liver disease characteristics, tumor parameters, treatment, and survival (OS) outcomes. OS analyses were performed using Kaplan-Meier method. RESULTS: One hundred and ninety-five patients with HCC were identified: 80.5% were male, and 22% were age 65 or older. Mean age at HCC diagnosis was 59.7 ± 9.8 years. Sixty-one point five percent of patients had Medicare or Medicaid; 4.1% were uninsured. Compared to African American (31.2%) and White (46.2%) patients, Hispanic patients (22.6%) were more likely to have diabetes (P = 0.0019), hyperlipidemia (P = 0.0001), nonalcoholic steatohepatitis (NASH) (P = 0.0021), end stage renal disease (P = 0.0057), and less likely to have hepatitis C virus (P < 0.0001) or a smoking history (P < 0.0001). Compared to African Americans, Hispanics were more likely to meet criteria for metabolic syndrome (P = 0.0491), had higher median MELD scores (P = 0.0159), ascites (P = 0.008), and encephalopathy (P = 0.0087). Hispanic patients with HCC had shorter OS than the other racial groups (P = 0.020), despite similarities in HCC parameters and treatment. CONCLUSION: In conclusion, Hispanic patients with HCC have higher incidence of modifiable metabolic risk factors including NASH, and shorter OS than African American and White patients.

Design of Customized Mobile Application for Patient Adherence to Oral Anticancer Medications Utilizing User-Centered Design.

Adherence and compliance to oral anticancer medications (OAMs) can be challenging for patients due to their complex regimens. The goal of this research project was to design an effective and engaging user interface (UI), based on user-centered design (UCD) and incorporate animations, to reinforce and improve patient's understanding of the key aspects of taking OAMs. This current paper encompasses the development process and describes the initial phase of the project, which focused on the design and development of the tablet-based educational application (app). A UCD approach was implemented by consulting with oncology clinicians and patients at an early stage of development. Animations were developed and incorporated to convey complex medical concepts and information. An iterative design process will help ensure that the tool is customized for patient engagement.

Conducting Retrospective Ontological Clinical Trials in ICD-9-CM in the Age of ICD-10-CM.

OBJECTIVE: To quantify the impact of International Classification of Disease 10th Revision Clinical Modification (ICD-10-CM) transition in cancer clinical trials by comparing coding accuracy and data discontinuity in backward ICD-10-CM to ICD-9-CM mapping via two tools, and to develop a standard ICD-9-CM and ICD-10-CM bridging methodology for retrospective analyses. BACKGROUND: While the transition to ICD-10-CM has been delayed until October 2015, its impact on cancer-related studies utilizing ICD-9-CM diagnoses has been inadequately explored. MATERIALS AND METHODS: Three high impact journals with broad national and international readerships were reviewed for cancer-related studies utilizing ICD-9-CM diagnoses codes in study design, methods, or results. Forward ICD-9-CM to ICD-10-CM mapping was performing using a translational methodology with the Motif web portal ICD-9-CM conversion tool. Backward mapping from ICD-10-CM to ICD-9-CM was performed using both Centers for Medicare and Medicaid Services (CMS) general equivalence mappings (GEMs) files and the Motif web portal tool. Generated ICD-9-CM codes were compared with the original ICD-9-CM codes to assess data accuracy and discontinuity. RESULTS: While both methods yielded additional ICD-9-CM codes, the CMS GEMs method provided incomplete coverage with 16 of the original ICD-9-CM codes missing, whereas the Motif web portal method provided complete coverage. Of these 16 codes, 12 ICD-9-CM codes were present in 2010 Illinois Medicaid data, and accounted for 0.52% of patient encounters and 0.35% of total Medicaid reimbursements. Extraneous ICD-9-CM codes from both methods (Centers for Medicare and Medicaid Services general equivalent mapping [CMS GEMs, n = 161; Motif web portal, n = 246]) in excess of original ICD-9-CM codes accounted for 2.1% and 2.3% of total patient encounters and 3.4% and 4.1% of total Medicaid reimbursements from the 2010 Illinois Medicare database. DISCUSSION: Longitudinal data analyses post-ICD-10-CM transition will require backward ICD-10-CM to ICD-9-CM coding, and data comparison for accuracy. Researchers must be aware that all methods for backward coding are not comparable in yielding original ICD-9-CM codes. CONCLUSIONS: The mandated delay is an opportunity for organizations to better understand areas of financial risk with regards to data management via backward coding. Our methodology is relevant for all healthcare-related coding data, and can be replicated by organizations as a strategy to mitigate financial risk.

Identifying clinically disruptive International Classification of Diseases 10th Revision Clinical Modification conversions to mitigate financial costs using an online tool.

PURPOSE: To quantify coding ambiguity in International Classification of Diseases Ninth Revision Clinical Modification conversions (ICD-9-CM) to ICD-10-CM mappings for hematology-oncology diagnoses within an Illinois Medicaid database and an academic cancer center database (University of Illinois Cancer Center [UICC]) with the goal of anticipating challenges during ICD-10-CM transition. METHODS: One data set of ICD-9-CM diagnosis codes came from the 2010 Illinois Department of Medicaid, filtered for diagnoses generated by hematology-oncology providers. The other data set of ICD-9-CM diagnosis codes came from UICC. Using a translational methodology via the Motif Web portal ICD-9-CM conversion tool, ICD-9-CM to ICD-10-CM code conversions were graphically mapped and evaluated for clinical loss of information. RESULTS: The transition to ICD-10-CM led to significant information loss, affecting 8% of total Medicaid codes and 1% of UICC codes; 39 ICD-9-CM codes with information loss accounted for 2.9% of total Medicaid reimbursements and 5.3% of UICC billing charges. CONCLUSION: Prior work stated hematology-oncology would be the least affected medical specialty. However, information loss affecting 5% of billing costs could evaporate the operating margin of a practice. By identifying codes at risk for complex transitions, the analytic tools described can be replicated for oncology practices to forecast areas requiring additional training and resource allocation. In summary, complex transitions and diagnosis codes associated with information loss within clinical oncology require additional attention during the transition to ICD-10-CM.

Targeting the HGF-cMET Axis in Hepatocellular Carcinoma.

Under normal physiological conditions, the hepatocyte growth factor (HGF) and its receptor, the MET transmembrane tyrosine kinase (cMET), are involved in embryogenesis, morphogenesis, and wound healing. The HGF-cMET axis promotes cell survival, proliferation, migration, and invasion via modulation of epithelial-mesenchymal interactions. Hepatocellular cancer (HCC) is the third most common cause of worldwide cancer-related mortality; advanced disease is associated with a paucity of therapeutic options and a five-year survival rate of only 10%. Dysregulation of the HGF-cMET pathway is implicated in HCC carcinogenesis and progression through activation of multiple signaling pathways; therefore, cMET inhibition is a promising therapeutic strategy for HCC treatment. The authors review HGF-cMET structure and function in normal tissue and in HCC, cMET inhibition in HCC, and future strategies for biomarker identification.