bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the quality of cancer treatment in a population of patients (pts) with metastatic colorectal cancer (mCRC) in routine clinical practice in different regions of Russia.
Authors: Fedyanin Mikhail , Aliyeva Shamai , Vladimirova Liubov Yu , Erdniev Sanal , Ivanov Alexander , Katkov Alexey , Kulik Valeriy , Kuzmina Evgeniya , Matyushina Elena , Nikitina Larisa , Orlova Rashida , Povyshev Anton Yurievich , Pshevlotskiy Eduard , Ramazanova Madina , Shalofast Olga , Smirnova Elena , Tkachuk Alexandra , Ulanova Natalya , Tjulandin Sergei
Published: September 2018

e18022

Background: In Russia, there are no federal screening programs for detecting early stage of colon cancer; therefore we can assess the impact of various factors that could potentially affect the mortality of pts with mCRC Methods: We conducted a survey with 13 question according treatment of pts with CRC in 17 regional comprehensive cancer centers in 14 regions of Russia, with a total population of 26.347 billion. Results of the survey were conducted by methods of descriptive statistics. Effects of factors on mortality rate in regions were analyzed by a regression model Results: Only 34% pts with stage II-III received adjuvant chemotherapy. Mutation status of KRAS gene has been evaluated only in 33% pts with mCRC. In 2013, metastasectomy was performed only 13% of pts. Only 80% of pts who needed systemic treatment received chemotherapy (CT): doublets of CT (XELOX/FOLFOX/FLOX or FOLFIRI/XELIRI/IFL) - 49%, monotherapy of fluoropyrimidines - 39% of pts, bevacizumab – in 14% and anti-EGFR antibodies - 5% pts. Only 14% of pts with mCRC was placed central vein devices. Second line CT was performed in 47% pts: doublets – in 54%, monotherapy of fluoropyrimidines - in 24% pts, bevacizumab - 13% and anti-EGFR antibody - 8%. Third-line treatment was performed in 25% of pts: anti-EGFR antibodies - in 7.5%. According to regression analysis adjuvant chemotherapy (р = 0.01), bevacizumab only in the 1st line (р = 0.01), and installation of central venous devises (р = 0.07) and anti-EGFR antibody in the 1st line (р = 0.1) in wtKRAS pts had independent positive effect on the mortality rate in regions. We revealed a significant reverse connection between a high mortality rate in the region and administration of fluoropyrimidine monotherapy as 1st line treatment of metastatic disease (p = 0.01) Conclusions: The mortality with colorectal cancer is depended of complex factors that reflect the health care organization in the region, both at the stage of treatment of pts with early-stage and metastatic disease. We revealed that targeted agents are the most effective only in the 1st line settings.
Predictors of treatment attrition in patients with metastatic colorectal cancer (mCRC).
Authors: Bahrabadi Arvin , Ruan Jenny , Gresham Gillian , Cheung Winson Y.
Published: September 2018

e18041

Background: Although the treatment landscape of cancer has evolved significantly with the introduction of novel and more efficacious drugs, the positive impact of these new therapies may be limited by attrition and ultimately non-exposure to later lines of therapy. Using a population-based cohort of mCRC, our aims were to characterize rates of attrition and determine factors associated with failure to receive each line of treatment. Methods: Medical records of patients who were diagnosed with mCRC from 2008-10 and referred to any 1 of 5 cancer centers in British Columbia were merged with systemic therapy data from the provincial pharmacy database. We classified patients into mutually exclusive treatment categories: a) receipt of all available lines of mCRC therapies; b) attrition directly attributable to disease, such as cancer progression or death; c) attrition attributable to other clinical factors, including toxicity, and d) attrition secondary to non-clinical factors, including personal/social circumstances. Multivariate logistic regression models were constructed to identify predictors. Results: We identified 525 eligible mCRC patients: median age 64 years, 57% men, 55% Caucasian, 68% ECOG 0/1, 41% and 35% never and ever smokers, respectively. The attrition rate was 40% (95% confidence interval [95% CI], 36%-44%) for first line treatment, 25% (95% CI, 19%-31%) for second line treatment and 14% (95% CI, 5.5%-22.5%) for third line. While cancer progression (31%) and chemo toxicity (30%) were the most common causes of attrition, other frequent reasons included death (20%) and patient preference (14%). On multivariable analysis, first-line treatment attrition was associated with worse baseline ECOG (odds ratio [OR], 1.92; p < 0.001) and older age at diagnosis of mCRC (OR, 1.04; p < 0.001). When we examined attrition over all lines, it was significantly correlated with worse ECOG (OR, 2.44; p < 0.001). Conclusions: Treatment attrition is a prevalent problem in mCRC and can hinder the benefits that would otherwise be possible with a sequential treatment algorithm. Some causes of attrition are potentially modifiable and may reflect opportunities for patients to maximize exposure to all lines of therapies.
The use of cardiovascular disease states as exclusion criteria in breast cancer trials: A 4-decade perspective.
Authors: Oren Michal , Oren Ohad , Mintzer David M.
Published: September 2018

e18053

Background: At the time of diagnosis, patients with breast cancer have a higher prevalence of cardiovascular risk factors than the general population. It is likely that the prevalence of actual cardiac disease is also increased, although no published data is available to support this claim. Individuals with breast cancer who also have heart disease are typically disqualified from clinical trials. We attempted to define the evolution of cardiovascular exclusion criteria in clinical trials of breast cancer over the decades. Methods: We searched the NEJM for original research in “breast cancer” published from 01/1980 to 12/2016. We reviewed the nature of cardiovascular disease as exclusion parameters as well as trends over time. Results: 20 RCTs were analysed, 5 from each decade (total # of patients 21,231). Mean number of cardiac exclusion criteria per study increased over the decades (1980s: 0; 1990s: 0.2; 2000s: 1; 2010s: 7). The most common cardiac exclusion criteria were CHF and recent MI (35% and 25% of studies, respectively). Factors associated with a higher likelihood of having a cardiac exclusion criteria were source of funding (industry vs. university: 77.7% vs. 18.1%, P-value 0.005) and study’s country of origin (U.S versus non-U.S: 57.1% versus 16.6%, P-value 0.02). Prior to 2010, the complete list of exclusion criteria was available with the manuscript. From 2010, it became embedded within the study’s protocol file (and not printed). Cardiovascular AEs were infrequent (1980s: 0.02%; 1990s: 0%, 2000s: 0.08%; 2010: 0.29%). Before 2000, studies described the significant cardiac toxicity in the manuscript. After 2000, a comprehensive registry of AEs contained within supplementary files became the norm. Conclusions: The use of cardiovascular exclusion criteria in clinical trials in breast cancer has become common over the past decades. Currently, it is almost impossible for a woman to enter a trial with even a single cardiac condition. Given that a sizeable fraction of breast cancer patients has cardiac disease, consideration should be given to narrowing the scope of cardiac exclusion criteria to allow more patients to participate, while making the results of those trials more broadly generalisable.
Treatment, outcomes, and impact of racial disparities on young adults with pancreatic cancer.
Authors: Alese Olatunji Boladale , Jiang Renjian , Shaib Walid Labib , Wu Christina Sing-Ying , Behera Madhusmita , El-Rayes Bassel F.
Published: September 2018

e18069

Background: Pancreatic cancer is a disease of the elderly. The treatment and outcomes of young adults with pancreatic cancer has not been well studied. The aim of this study is to describe the treatment, outcomes, and impact of race in young adults with pancreatic cancer. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2004 and 2013. Univariate and multivariate testing was done to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between patient characteristics, time intervals and survival. Results: A total of 9,657 patients between 18 and 50 years of age were identified. The mean age was 45.4 years (SD±4.6), with a male preponderance (58.3%). Distribution across stages I-IV was 6.1%, 31.1%, 13.9% and 48.8% consecutively, and was similar across all racial groups. About 30.9% of patients underwent resection of the primary pancreatic tumor. Univariate analysis showed survival difference between ages 18-34 vs. 35-50 years old (HR 0.81; 0.71-0.92; p<0.001). On multivariable analysis, Hispanics had significantly higher survival rates than non-Hispanic Whites (NHW) (HR 0.7; 0.64-0.76; p<0.001). Compared to Blacks, Hispanics were more likely to benefit from surgical resection (HR 0.76; 0.61-0.94; p=0.011) and chemotherapy administration (HR 0.78; 0.69-0.88; p<0.001). Overall, patients treated between 2009 and 2013 had higher survival rates compared to 2004-2008 (HR 0.86; 0.82-0.91; p<0.001). The improvement in 5-year overall survival rates over time was highest in American Indians and Asian/Pacific Islanders (16.6% vs. 6.5%); Blacks (10.6% vs. 8.5%) and Hispanics (14.5% vs. 12.6%). NHWs marginally improved from 8.4% to 9.8%. Conclusions: Survival in pancreatic cancer patients younger than 50 years has improved over time, with major gains in minority populations. [Table: see text]
Surgeon influence on receipt of contralateral prophylactic mastectomy for breast cancer.
Authors: Katz Steven J. , Morrow Monica , Hawley Sarah T. , Jagsi Reshma
Published: September 2018

e18145

Background: Rates of contralateral prophylactic mastectomy (CPM) have markedly increased but virtually nothing is known about the influence of surgeons on variability of the procedure in the community. We quantified the influence of attending surgeon on rates of CPM and clinician attitudes that explained it. Methods: Population-based sample of 7810 patients newly diagnosed with curable breast cancer (BC) in Georgia and Los Angeles County treated in 2013-15 were surveyed (response rate 70%, n = 5018) and responses were linked to 488 attending surgeons through patient report. Surveys were sent to surgeons towards the end of the patient data collection period and 377 completed them (response 77%). We linked 3718 respondent patients with unilateral disease to 365 respondent surgeons. Two surgeon attitudes scales were developed based on a scenario of a patient with early stage BC at average risk of a 2nd primary cancer: 1) favors initial breast conservation and, 2) reluctance to perform CPM if patient asks. We did multilevel analyses using information from patient and surgeon reports merged to SEER data. Results: A model including patient clinical factors and surgeon id predicted CPM extremely well as it explained 37% of the variability in the likelihood of CPM. Patient factors explained 16% of the variability but the surgeon identifier alone explained even more (21%). The odds of a patient receiving CPM increased 3-fold (95% CI 1.9, 4.7) if she saw a surgeon with a practice approach one standard deviation above a surgeon with the average CPM rate (15%). One quarter (24%) of the surgeon influence was explained by attending attitudes about initial recommendations for surgery and responses to patient requests for CPM. The rate of CPM was 34% for surgeons who least favored initial breast conservation and were least reluctant to perform CPM. By contrast, the estimated rate was 5% for surgeons who most favored initial breast conservation and were most reluctant to perform CPM if asked. Conclusions: Attending surgeons exert strong influence on the likelihood of receipt of CPM for breast cancer. Variations in surgeon attitudes about recommendation for surgery and response to patients request for CPM explain a substantial amount of this influence.
The European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) in daily practice: A real-life feasibility analysis at the Medical University Vienna.
Authors: Kiesewetter Barbara , Raderer Markus , Steger Guenther G. , Bartsch Rupert , Pirker Robert , Zochbauer-Muller Sabine , Prager Gerald W. , Krainer Michael , Preusser Matthias , Schmidinger Manuela , Fuereder Thorsten , Marosi Christine , Locker Gottfried J. , Brodowicz Thomas , Zielinski Christoph
Published: September 2018

e18151

Background: The ESMO-MCBS constitutes a new tool to quantify the clinical benefit that may be anticipated from a novel anticancer treatment based on original data from randomized or controlled trials. In contrast to comparable concepts, this score appears somehow unique as it concentrates on the clinical benefit for the individual patient irrespective of socioeconomic factors. Being introduced 2015; the MCBS has excited great public interest in Europe in the last year. We present here the first feasibility analysis of the MCBS under real-life conditions at the Medical University Vienna (MUV), one of Europe’s largest centers. Methods: This study evaluated systematically the practicability of the MCBS for advanced/metastatic malignant diseases treated at the MUV ( > 15 tumor entities). A 3-step approach including data analysis of regimens in regular use, assessment of scores (1 = not recommended to 5 = highly recommended) and evaluation of results with a focus on clinical feasibility was applied. Results: In the majority of tumor entities and clinical settings the assessed MCBS scores were consistent with our daily practice and particularly with our 1st line standards for common tumors like metastatic breast-, colorectal- or lung cancer. However, there were certain limitations including orphan diseases with a lack of randomized data (e.g. rare sarcoma subtypes) or tumor entities with cascade like treatment settings (e.g. colorectal cancer). Interestingly, new immunomodulatory approaches and checkpoint inhibitors in particular, scored strikingly high in comparison to conventional chemo due to a favorable toxicity profile, positive influence on quality of life and strong efficacy data in many cases. A broad selection of data will be presented at the meeting. Conclusions: Our analysis encompasses a wide range of tumor entities and clinical settings and reflects the daily experience of a university clinic. Mostly, the MCBS scores supported treatment decisions based on the clinical benefit to be expected from a novel therapy and might also support socioeconomic questions exemplified by high scoring of immunomodulatory approaches.
Discordant breast cancer: Low risk genomic, high risk pathologic.
Authors: Blankenship Leann , Ezekwudo Daniel , Jaiyesimi Ishmael A. , Alassi Osama , Stender Michael J. , Gaikazian Susanna S.
Published: September 2018

e18160

Background: Studies using the 21-gene recurrence score (RS) have shown low risk pathologic features and RS breast cancers do not benefit from systemic chemotherapy (CTx). However, data is lacking for patients with discordant risk factors and which feature, genomic or clinical, plays more of a role in determining outcomes. Methods: Retrospective analysis was conducted to identify breast cancer patients with discordant features, defined as low genomic/high pathologic factors, from 2011 to 2016. Patients were hormone-receptor positive with RS < 18 and had ³ 2 high risk factors: tumor size ³2cm, lymph node (LN) positivity, or grade 2-3 disease. Results: There were 469 patients with low risk RS were identified of whom 118 met discordant risk criteria. Patients management is depicted in Table 1. Of the 118 discordant patients, 22 had breast cancer recurrence as either metastatic (1) or locoregional (21); 11 being ipsilateral while the remainder were contralateral. Patients with ipsilateral recurrences had partial mastectomy and radiotherapy as initial management. CTx was received in 30 patients despite low RS. Recurrences occurred in 31.8% of patients who received adjuvant CTx. The majority of recurrences occurred >5 years after initial diagnosis. Conclusions: Our results show both genomic and pathologic features were important in determining the need for CTx in early stage breast cancer but neither had a greater impact. Thus, we advocate a more comprehensive and individualized approach, taking into account comorbidities, genomic, and pathologic features, for addition of CTx to standard hormonal therapy. Further studies are needed to determine the proper treatment of this unique patient population. [Table: see text]
Evaluating treatment patterns of relapsed acute myeloid leukemia (AML) among the elderly in the United States.
Authors: Zhang Qisu , Xie Lin , Baser Onur , McGuire Michael
Published: September 2018

e18161

Background: The type and place of treatment in relapsed AML has not been explored in a large national data set. The goal of this study is to examine treatment patterns among elderly patients (pts) with relapsed AML. Methods: Elderly pts (age ≥ 65 years) with an AML diagnosis (ICD-9-CM: 205.x) were identified using Medicare data from Jan 2010 to Dec 2014. The index date was the first AML treatment date within 30 days of diagnosis. Relapsed pts were identified with ICD-9-CM 205.02 or a claim for AML therapy after a ≥ 120-day treatment-free gap. Pts were required to have continuous enrollment 12 months before AML diagnosis and 6 months after, and no pre-diagnosis claims for blood cancer, chemotherapy, radiotherapy, or AML-related surgery. Transfusion dependence (TD) was defined as ≥ 2 transfusions within an 8-week period. The type and place of treatment for relapsed pts with both 1st- and 2nd-line therapy was examined. Results: 1,726 pts who received treatment for relapsed AML were included in the study. The 30- and 60-day mortality rates from the date of relapse treatment were 19.6% and 33.6%. During 1st-line therapy, 28.6% of pts received inpatient chemotherapy only, 59.1% received both inpatient and outpatient therapy (median inpatient length of stay [LOS]: 32 days), and 3.8% received outpatient therapy only. The most frequent outpatient therapies were hypomethylating agents and supportive therapies, e.g. G-CSF, anti-infectives. 11.3% of inpatients were given a bone marrow transplant (BMT). Additionally, 90.1% of pts received blood transfusions at an average rate of 8.9 per year, and 77.2% of pts were TD. During 2nd-line therapy, 19.6% of relapsed pts received inpatient chemotherapy only, 41.2% received both inpatient and outpatient therapy (median inpatient LOS: 7 days), and 9.3% received outpatient therapy only. Outpatient therapies were similar to those seen at 1st line. 10.3% of inpatients were given a BMT. 80.9% of pts received blood transfusions at an average rate of 19.7 per year, and 60.4% of pts were TD. Conclusions: Current treatment options available for relapsed AML pts are associated with a significant treatment burden at both 1st and 2nd lines of therapy, as well as a high early-mortality rate.
Physician communication and patient understanding of molecular testing of tumors.
Authors: Pentz Rebecca D. , Pocock Rachel Hannah , Pinheiro Ana M , Switchenko Jeffrey M. , Dixon Margie D
Published: September 2018

e18217

Background: Molecular testing is being used with increasing prevalence to diagnose and treat cancer. Novel technical terminology is required to describe this testing to patients; however, it is unknown what language is being used and whether this language is understood, This study aimed to determine how oncologists describe this testing to patients and whether patients understand the technical terms and conceptual topics used by physicians. Methods: Patients and oncologists were consented for this study at one academic and two community hospitals. Conversations including a discussion of molecular testing were recorded; patients were then interviewed to assess their understanding of the terminology and topics described by their physicians. Recordings were transcribed and qualitatively analyzed; descriptive statistics were calculated from the coded data to identify the most frequently used technical terms and conceptual topics, assess overall patient understanding, and calculate an understanding score for each patient. Results: Sixty conversations about molecular testing were observed and recorded between 60 patients and 19 physicians. Thirty-four different technical terms were used by oncologists to describe 5 technical themes (mutation, molecular testing, targeted therapy, driver mutation, and biomarker). Patients understood 45% of undefined technical terms and 43% of defined technical terms. Physicians explained why the molecular testing was ordered in 67% of conversations, with 71% of patients demonstrating understanding, and how the testing would determine the patient’s treatment in 93% of conversations, with 80% of patients demonstrating understanding. Conclusions: Oncologists use variable language to describe molecular testing to patients. Patients do not understand most of the terms being used and defining technical terms does not improve patient understanding. Despite this, oncologists are effectively communicating the purpose of molecular testing and the effect of such testing on patient treatment. Future studies are warranted to determine which language and methods are most effective for describing molecular testing to patients. Guidelines and training for oncologists may be beneficial.
Customized electronic alerts to boost pneumococcal vaccinations in high risk cancer patients.
Authors: Bhatt Ananta , Hort Shoshana , Gelb Daniel J , MacKenzie Todd , Lansigan Frederick
Published: September 2018

e18227

Background: Streptococcus pneumoniae remains a leading cause of serious illness, including bacteremia, meningitis, and pneumonia among adults in the United States. Approximately 10% of all patients with invasive pneumococcal disease die of their illness, but case-fatality rates are higher for immunocompromised adults including cancer patients. Current Center for Disease Control (CDC) guidelines recommend routine use of 13-valent (Prevnar 13) and 23-valent (Pneumovax 23) pneumococcal vaccines (PV) for immunocompromised patients. We conducted a quality improvement (QI) project utilizing our electronic medical record (EMR) system to improve PV compliance (PVC) rates in our patients. Methods: We created automatic reminders called best practice alerts (BPA) and linked them to a smart order set within our EMR that appeared upon opening patient charts. The smart set ordered the correct vaccine in sequence based on CDC guidelines. From August 2015- January 2017, we implemented this BPA for one of six hematology providers and the remaining providers were provided with verbal guidelines and reminders to administer PV to their patients. Results: At baseline only 22% of 3000 hematology patients within the practice had received PV. The pilot provider with the BPA linked to a smart order set within the EMR improved PVC within his patients from 23% to 66%. Providers who were just given verbal guidelines improved PVC from an average of 22% to 45%. The difference in the improvement between the pilot provider and the reference group is 21% (p < 0.001). Conclusions: In an EMR era, we took advantage of the tools within our system to improve PVC rates. BPA linked to a smart order set within the EMR provided better means of improving PVC than verbal prompts in high-risk immunocompromised patients. Additionally, the increase in PVC throughout the hematology practice is due to primary care providers using similar reminders within the same EMR. The PV BPA will be conducted as a standard of care in our clinic and will be expanded to oncology patients as well.
Baseline characteristics as predictors of adjuvant chemotherapy (AC) toxicities in stage III colorectal cancer (CRC) patients.
Authors: Watanabe Akie , Yang Charlie , Cheung Winson Y.
Published: September 2018

e18237

Background: Toxicities acquired from AC can impact quality of life. Baseline patient characteristics such as age, sex, ECOG, tumor location, TNM staging, and comorbidities are frequently considered in AC treatment decision-making, but their associations with common toxicity outcomes remain unclear. Methods: We used a population-based cohort of CRC patients to test our hypothesis. We reviewed individuals treated with adjuvant monotherapy (Capecitabine) or combination therapy (FOLFOX or CAPOX) within 12 weeks of curative resection at any 1 of 6 cancer centers in British Columbia, and determined the associations between baseline characteristics and toxicity outcomes. Results: Among 371 patients, median age was 65 (range 26-86) years, 51.5% were men, and 14% were ECOG ≥2. In this cohort, 41% received monotherapy and 59% received combination therapy. For monotherapy, univariate analyses found that age, sex, ECOG, and pre-treatment anemia were associated with hematological toxicities ( P < 0.05). Likewise, tumor location and TNM staging were associated with gastrointestinal (GI) toxicities ( P < 0.05). On multivariate analyses, hematological toxicities were more likely to develop with old age (≥70) (OR 3.30, 95% CI 1.17-9.37, P= 0.025) and pre-treatment anemia (OR 23.18, 95% CI 6.36-84.48, P= 0.001), while GI toxicities were less likely to occur with a left-sided tumor (OR 0.38, 95% CI 0.15-0.99, P= 0.047). In univariate analyses of combination therapy, sex and pre-treatment anemia were also associated with hematological toxicities, while cardiac and/or respiratory comorbidities were associated with neuropathy ( P < 0.05). In multivariate analyses, however, only female sex was predictive of hematological toxicities (OR 5.13, 95% CI 2.08-12.68, P= 0.001) and neuropathy was less likely to develop with cardiac and/or respiratory comorbidities (OR 0.23, 95% CI 0.07-0.81, P= 0.023). Further analyses did not show any consistent correlations between other baseline characteristics and toxicity outcomes. Conclusions: Readily available baseline patients characteristics are associated with the development of specific side effects, which can be used to better inform AC discussions.
The impact of polypharmacy and comorbidities on surgical morbidity and mortality in patients with gynecological malignancies: Results of a prospective study in 237 patients.
Authors: Inci Guelhan , Woopen Hannah , Richter Rolf , Chekerov Radoslav , Muallem Mustafa Zelal , Sehouli Jalid
Published: September 2018

e18255

Background: Physicians need to risk-stratify their patients preoperatively to adjust the radicality and the indication of surgery. So far, there are only retrospective and limiting data available. Aim of this study is to evaluate the predictive clinical characteristics such as polypharmacy and Charlson-Comorbidity Index (CCI) for postoperative complications in patients undergoing gynecologic cancer surgery. Methods: This is a prospective cohort study of patients undergoing gynecologic cancer surgery at a tertiary care academic center from October 2015 through January 2017. Surgical complications were graded using validated Clavien-Dindo criteria. Using logistic regression, we identified demographic and predictive clinical characteristics for postoperative complications. Results: Out of the 237 enrolled patients 41(17.3%) experienced a grade≥3b complication. Within 30 days of surgery, 9 (3.8%) patients has died. Charlson Comorbidity index (CCI)> 2(p<0.015, OR 2.33, 95% CI 1.18-4.61), polypharmacy (p<0.001, OR 3.40, 95% CI 1.63-7.10), ASA (p<0.0001, OR 2.98, 95% CI 1.65-5.38), BMI>25kg/m2 (p<0.001, OR 4.25, 95% CI 1.86-9.69), preoperative albumin<3.5 g/dl (p<0.009, OR 3.22, 95% CI 1.33-7.79) and potassium < 3.6 mmol/L (p=0.007, OR 5.11, 95% CI 1.55-16.81) were predictive for complications grade≥3b. A multivariable model included duration of surgery (p=0.012, OR 1.26, 95% CI 1.05-1.52), ASA (p=0.01, OR 2.60, 95% CI 1.20-5.60), preoperative albumin<3.5 g/dl (p=0.028, OR 3.37, 95% CI 1.14-10.00), BMI >25kg/m2 (p=0.009, OR 3.81, 95% CI 1.40-10.35) and potassium < 3.6 mmol/L (p=0.02, OR 3.69, 95% CI 1.20-11.38) was predictive of 30-day Morbidity and Mortality. Age (p=0.49, OR 0.89, 95% CI 0.95-1.02), CCI > 2(p=0.88, OR 1.06, 95% CI 0.42-2.69) and polypharmacy (p=0.65, OR 1.26, 95% CI 0.41-3.98) showed no association for postoperative complications. Conclusions: Only ASA, BMI, preoperative albumin and potassium are associated with severe postoperative complications in patients undergoing gynecologic cancer surgery. Subsequent studies should confirm this result to identify better frail cancer patients.
Venous thromboembolism incidence in radiation oncology: Retrospective trial.
Authors: Cherkashin Mikhail A , Berezina Natalia A
Published: September 2018

e18289

Background: Venous thromboembolism (VTE) prevention in oncology patients during external beam radiation therapy (RT) in outpatient setting is the challenging question. We performed analysis of our own data. The aim of study is the clear assessment of VTE incidence in these patients Methods: In retrospective analysis 5134 patients' medical records were included (2612 with RT and 2522 with chemotherapy). Inclusion criteria were: RT in outpatient setting and chemotherapy in outpatient setting. Exclusion criteria: combined radiochemotherapy, hospitalzation, central venous catheter, palliative treatment. 487 patients were selected for the final analysis and stratified in 3 groups: group I (n = 165) 3D-conformal RT for brain tumors or brain metastasis; group II (n = 158) RT for body tumors (abdominal, retroabdominal, pelvic, chest, breast); group III (n = 164) was control –brain and body tumors on chemotherapy. Mean fraction numbers were 25 (11 - 32), mean total dose – 52 Gy (22 - 66). VTE assessment based on clinical data, ultrasound examination (US) and chest CT. Statistical analysis was performed by OpenEpi, Version 3 software pack. Results: Deep vein thrombosis (DVT) was detected in 10 cases (6.06%) in group I, 4 cases in group II and 4 case in control group. VTE patients has a different tumors (astrocytomas, brain trunk tumors, skull basis cancer, rectal cancer, breast cancer). 3 patients were available for long-term outcomes assessment (12 months after radiation therapy). During 1-year period we haven’t detected thrombosis recurrence. One patient on 11th follow-up month was exposed with repeated course of RT without any complications. The difference between VTE incidence for group I and group III characterized by statistical significance (p = 0.018). Risk difference for these groups was 5% (p < 0.05). Conclusions: Based on study results we suggest that external beam radiation therapy is potentially an independent risk factor for VTE development even in outpatient settings. High degree of clinical suspicion and aggressive diagnostic work-up in case of suspicion is necessary. In our opinion low molecular weight heparins prevention should be considered at least during active radiation therapy.
Oncological supportive-care unit (OSU): An effective toxicity management model.
Authors: Mirabile Aurora , Foglia Emanuela , Frigo Fiorenza , Del Grosso Elisabetta , Barbarini Lucia , Bovio Antonella , Butti Chiara , Ciambelli Fabrizio , Pauli Sergio , Ricci Isabella , Gargiola Elisabetta , Aloisio Enrica , Oliva Giovanna , Artale Salvatore Agatino
Published: September 2018

e18301

Background: Oncological patients (pts) frequently experience treatment-related toxicities worsening outcome. According to literature data, 23% - 50% emergency department (ED) and/or hospital admissions in this setting could be avoidable and hesitate in higher management costs and worse quality of life (QoL). Cancer treatment adherence rate is 27% - 87%, mostly related to chemotherapy and post-surgical side effects. Since May 2014 we established an OSU to improve clinical outcome and treatment adherence, to reduce ED access/hospital admissions and toxicities management costs. Methods: All OSU data have been recorded in a database which includes daily management costs into an Italian regional regimen called MAC (Complex Ambulatory Macro-activities). ED accesses were recorded by our “First aid ED operative system”. Hospitalizations costs were evaluated according to regional DRG (Diagnosis Related Group) value and Hospital Discharge Register (HDR). All pts admitted to OSU should answer to two validated questionnaires regarding QoL and anxiety: FACT-G (General FunctionalAssessment Cancer Therapy) and HADS (Hospital Anxiety and depression Scale). We compared toxicities management costs 20 months before and 20 months during OSU. Results: From May 2014 to December 2015, 302/719 pts were admitted to OSU for a supportive care therapy. We obtained the reduction of the costs of the ED access/hospital admission to 52%, while the gain in management was 59% (see table). PS ECOG improved in 9 (18%) pts while it was unchanged in 41 (82%) pts. Adherence to oncologic treatment was satisfactory (95%) and the average values of total FACT and HADS in the follow-up phase improved compared to baseline in 63% and 43% of pts respectively. Conclusions: The interim analysis suggests that OSU improves clinical outcome in terms of QoL and treatment adherence. Moreover, our OSU model demonstrated the possibility to reduce toxicity-related ED accesses/hospital admissions and management costs. [Table: see text]
Predictors of no-show among international patients with cancer: A 4-year analysis.
Authors: Bhulani Nizar , Xiao Lianchun , Hassan Manal , Lenzi Renato
Published: September 2018

e18302

Background: Patient no-show (NSh) for scheduled medical appointments negatively impacts quality of care, impedes optimal use of resources, has negative economic consequences secondary to missed appointments, and uncovered referral processing costs. International patients (IntlPts) present challenging financial/travel arrangements and cultural and linguistic needs. There are currently very limited data regarding numbers of IntlPts visiting the United States for medical care and no data regarding NSh rates. The purpose of this study was to quantify costs and identify IntlPts-related variables correlating with NSh to develop interventions aimed at minimizing the associated negative financial consequences. Methods: A retrospective study of IntlPts accepted and scheduled for an appointment at the International Assessment Center at MD Anderson in fiscal years 2010 – 2013 was conducted. Overall 52 variables were evaluated that included socio-demographic and clinical patient characteristics, financial responsibility, and appointment timeline. For univariate analysis, Chi-square test and Wilcoxon rank sum test were applied. For multivariate analysis, a multivariate logistic regression model was fit. The multivariate logistic model with independent covariates was used to construct a nomogram. The Time Driven Activity-Based Cost method was used to assess the cost of processing referral requests. Results: Of 1031 IntlPts scheduled, 311 (30%) were NSh. NSh was significantly associated (p < 0.05) with country of origin, payer, diagnosis, referral source, disease stage, patient-delayed appointment date, number of symptoms, pain, bleeding, fatigue, dysphagia, jaundice, neurological symptoms, comorbidities, and appointment lag time. Direct operational costs were calculated using process maps and TDABC. Conclusions: These results provide the groundwork to understand operational costs and predictors of no-show of oncology IntlPts. Having knowledge of predictive factors for NSh in a new patient outpatient setting represents a necessary step towards decreasing its frequency, addressing associated costs, optimizing continuity of care, and ultimately improving outcomes and value of the provided care.
Conceptualization of an indication-specific pricing model to assess potential savings to a U.S. health plan.
Authors: Shah Sandip , Black Joseph , Ramesh Vidya , Shao Dong , Narayanan Siva
Published: September 2018

e18315

Background: Value based pricing has become a topic of increasing public attention and scrutiny. An Indication Specific Pricing (ISP) allows price setting relative to the level of benefit provided in a given indication and patient population, with the potential for price to vary based on value in the concerned indication(s). We quantified the impact of deploying an ISP scheme on 5-year Afinitor (everolimus) expenditures for a hypothetical health plan of 5M covered lives in the U.S., taking into account three indications: HER2- breast cancer, renal cell carcinoma, and pancreatic cancer. Methods: We constructed an Excel-based model to understand future expenditures on an annual basis utilizing an ISP scheme against a more traditional single contracted price. Key inputs for the model include price per pill (average selling price (ASP)), forecasted annual number of patients per indication (based on 5M covered lives), and compliance rate. Results from the Sloan Kettering “DrugAbacus” pricing project were leveraged to estimate indication-level prices based on their assessment of efficacy, tolerability, and unmet need for Afinitor in each of the indications; actual ISP prices originally used by Sloan Kettering in their model were reweighted and adjusted. Results: As the DrugAbacus price calculated for each indication was lower than the current ASP for Afinitor, use of an ISP methodology resulted in a 9.3% decrease in five year expenditures for Afinitor ($136.9M for a traditional single price vs. $124.1M for an ISP model). Conclusions: US Payers could consider assessing the value a therapeutic intervention brings to each approved indication using ISP in an effort to lower total pharmaceutical-related healthcare costs. Drug manufacturers may benefit from considering relative product value in each potential indication to assess commercial attractiveness and focus evidence generation strategies on those indications seen as most valuable, to support price negotiations.
Efficacy, safety, tolerability and price of newly approved drugs in solid tumors.
Authors: Barnes Tristan Alexandra , Amir Eitan , Templeton Arnoud J. , Gomez Garcia Susana , Navarro Beatriz , Seruga Bostjan , Ocana Alberto
Published: September 2018

e18336

Background: New anti-cancer drugs utilize diverse mechanisms of action. Here we evaluate their differential efficacy, safety, tolerability and price. Methods: Drugs approved for the treatment of solid tumors between 2000 and 2015 were identified and analyzed in subgroups: agents targeting oncogenes or dysregulated pathways (group 1), anti-angiogenic drugs (group 2), immunotherapy (group 3), and chemotherapy (group 4). Hazard ratios (HRs) were extracted from the reports of randomized trials supporting registration and pooled in a meta-analysis. Odds ratios (ORs) for rates of toxic death, treatment discontinuation and grade 3-4 toxicity were compared relative to control groups. The Micromedex Red Book was used to calculate the monthly price of each agent. Results: Analysis included 74 studies comprising 48,527 patients. Progression-free survival (PFS) was improved to a lesser degree with groups 3 and 4 than with groups 1 and 2, (pooled HR:0.54, 0.56, 0.63, and 0.76 for groups 1–4 respectively, p for difference < 0.001). Compared to PFS, there was a lower magnitude of improvement overall survival in all groups and the degree of benefit was less for group 4 than for other groups (pooled HR:0.77, 0.78, 0.68, and 0.83 for groups 1–4 respectively, p for difference = 0.007). Compared to control groups in individual trials, immunotherapy was associated with better safety and tolerability than other groups. Drug prices have increased over time with no statistically significant difference between groups. There was limited to no correlation between drug pricing and efficacy. Conclusions: Compared to control groups, chemotherapy improves efficacy to a lesser degree than the other groups. Immunotherapy appears to have better safety and tolerability profile compared to other cancer therapies. Market price of drugs is not related to efficacy.
Association of pre-allogeneic hematopoietic stem cell transplant 25-hydroxy-vitamin D level and development of acute skin graft-versus-host-disease: A retrospective analysis of 154 patients.
Authors: Joseph Ranjit , Jabbar Seema , Reddy Manasa , Houghton Damon Eugene , Yun Trull , Tan Xainming , Hashim Ibrahim
Published: September 2018

e18539

Background: The pathophysiology of acute skin graft versus host disease (asGVHD) is thought to be initiated when donor T cells encounter recipient dendritic cells (DC) and become activated. Studies have shown that vitamin D (VD) inhibits DC maturation, polarizes T cell populations toward Th2 cytokine phenotype, And biases toward tolerating T cell populations. We analyzed pre-SCT serum vitamin D levels and sought to determine an association with development of acute skin GVHD. Methods: 154 patients, with matched SCT at UTSW Medical Center from December 2007 to December 2014, and who had serum samples banked prior to conditioning were included in the analysis. Pertinent data were extracted from the UTSW BMT database and EMR. Serum samples collected 1-3 months prior to SCT were used to detect 25-hydroxyvitamin D (VD) concentrations. Cumulative incidence (CI) of asGVHD grade II-IV were assessed within 100 days post-SCT. A significantl difference (p-value = 0.026, Breslow-Day test) in the associations between Vit D and asGVHD for patients under RIC and ABLgroups was present, so we analyzed the primary endpoint, time to asGVHD since SCT, separately among two these 2 groups. CI functions were constructed with death and relapse as competing risks. Results: Out of 154 patients, 93 were male, mean age was 51, range 20-72 and median VD was 21 ng/ml (range 7.1-63.3). There were 112 patients with VD < 25 ng/mL (VD < 25) and 41 with VD ≥ 25 ng/mL (VD≥25). Age, conditioning regimen, donor type, cell source, ABO compatibility, GVHD prophylaxis were similar in both groups. Overall CI asGVHD was 24%. CI of asGVHD was 23.8% in VD≥25 and 24.1% in VD < 25. Patients were then analyzed separately with respect to type of conditioning regimen they received (Ablative (ABL) vs Reducing intensity (RIC)). Figure 1A shows that in the ABL group the CI of asGVHD appears increased in patient with VitD≥25 (40% vs 27.1%, p = 0.27). In contrast, Figure 1B shows that in RIC group the CI of asGVHD is higher for those with VD < 25 (4.8% vs 24.1% , p = 0.05). Conclusions: After accounting for competing factors, KM analysis in the RIC group showed that patients with VD level < 25 ng/mL were at a higher risk of developing asGVHD. Further studies to clarify the association between VD status and development of asGVHD are warranted.
Survival outcomes in patients with chronic phase chronic myeloid leukemia (CP-CML) receiving third- or subsequent line (3L) treatment prior to the availability of ponatinib.
Authors: Stellato Daniel R , McGarry Lisa , Huang Hui , Hastings Shaina , Delea Thomas E.
Published: September 2018

e18553

Background: PACE was a phase 2 single-arm trial of ponatinib, a 3rd-generation tyrosine kinase inhibitor (TKI), in 449 highly-refractory patients with CML or Philadelphia-chromosome positive (Ph+) acute lymphocytic leukemia (ALL) or who had the BCR-ABL T315I mutation. Overall survival (OS) for 3L CP-CML patients in PACE at 1, 2, 3 and 4 years was estimated to be 91%, 83%, 80%, and 79%, respectively. Expected survival for 3L CP-CML patients prior to the availability of ponatinib has not been documented. Methods: A systematic literature review was conducted to estimate OS in patients with CP-CML receiving 3L treatment prior to ponatinib. Studies were identified from a review by Lipton et al. (2015), updated with studies identified from searches of electronic databases (MEDLINE, EMBASE, Cochrane Libraries) and abstract databases of key conferences. Landmark and median survival were extracted from study reports. Pseudo-individual patient data (IPD) for survival outcomes were derived from digitized Kaplan-Meier (KM) survival curves then pooled and analyzed using KM methods. Results: Fifteen studies (717 patients) were identified that reported median, landmark, or KM curves for survival outcomes for CP-CML patients receiving 3L treatment without ponatinib. KM curves for OS were obtained for 6 arms (3 nilotinib and/or dasatinib; 3 other TKIs). OS at 1, 2 and 3 years based on the pooled IPD is reported in the Table. To avoid confounding of OS from post-progression treatment with ponatinib, 1 study was excluded that included follow-up after the date of ponatinib’s approval. Conclusions: EstimatedOS in patients with CP-CML receiving 3L treatment prior to ponatinib appears to be shorter than that observed among ponatinib-treated patients in PACE: 4-year survival probability in PACE is higher than estimated 2-year survival probability prior to ponatinib. Further analyses are needed to identify and adjust for potentially confounding factors. [Table: see text]
Treatment of essential thrombocytopenia patients intolerant/ resistant to hydroxyurea: A physician survey.
Authors: Nejadnik Bijan , Mascarenhas John , Rappaport Karen M , Lu Biao , Gagnon Bruno M , Verstovsek Srdan
Published: September 2018

e18565

Introduction: Hydroxyurea (HU) is deemed first-line cytoreductive therapy for patients with essential thrombocythemia (ET) at high-risk for vascular complications with 20-25% of patients developing HU intolerance/ resistance (HUIR). Up to one-third of patients taking anagrelide, often the 2nd line drug of choice, are also unable to tolerate its side effects (cardiovascular and gastrointestinal). A review of the medical literature suggests widespread support for individualized treatment plans in ET with multiple options, including HU, anagrelide, interferon and busulfan, but little is known about physician practice. Methods: We contracted with a research company to perform an internet survey of 20 academic and 20 community hematologists to assess treatment practices for HUIR ET patients. We assumed a 25% rate of resistance to anagrelide. Results: Academic and community physicians reported 22% and 25% HUIR rates, respectively. An estimated 60% and 44% of HUIR patients in academic and community settings, respectively, would undergo treatment with an agent other than anagrelide (interferon, busulfan, or ruxolitinib) in 2nd or 3rd line treatments. Physicians not using anagrelide as 2nd line therapy also would not use it as 3rdline therapy. Anagrelide is used more frequently in the community setting. Conclusions: About 50% of HUIR patients are treated with agents other than anagrelide as 2nd/ 3rdline therapy. Reasons for practice variation in the treatment of ET remain poorly understood. [Table: see text]