bluuebunny/crossref_metadata_2025 huggingface dataset:
The next generation of quality improvement at MSK: Turning chemotherapy process delays into chemo express.
Authors: Tota Jennifer , Levine Kathleen , Gordon Jeanine , Baldwin Abigail , Wald Jodi , Salvaggio Rori , Lee-Teh Melissa , Freeswick Scott , O'Cearbhaill Roisin , Reidy Diane Lauren
Published: September 2018

e18230

Background: Chemotherapy wait times can dramatically affect patient experience. MSK’s largest outpatient facility has 76 infusion spaces and 250-300 daily visits. A retrospective review of the facility’s infusion area wait times suggested that the lab (where all patients go to get their vitals and blood drawn) was a major bottleneck leading to process delays in infusion. Methods: We conducted a pilot program using a multi-pronged approach. Our goal was to decrease wait time from 40 minutes to an average of 15 minutes. Our initiative was defined as follows: (1) to redefine lab parameters that are relevant for toxicity and to only consider drawing those necessary labs; additionally, we created guidelines for timing of the labs prior to infusion treatment, (2) to introduce a program known as “ChemoExpress” which offers patients the opportunity to get blood work done prior to the day of their infusion appointment. After the labs result, the outpatient RN calls the patient, assesses symptoms and “clears them” for treatment cueing the pharmacy to prepare and “premix” the drug on the day of treatment. Results: 150 patients have enrolled in ChemoExpress. Patient satisfaction was high based on patient satisfaction surveys (n = 20). Average wait time was 9 minutes (76% less) in ChemoExpress participants as compared to an average wait of 39 minutes for those who did not participate in ChemoExpress. Conclusions: Implementing a process that enables patients to have their bloodwork drawn prior to the day of treatment and drugs prepared in advance of their treatment appointment results in greater efficiency in the overall workflow. It also offers the patient a lower wait time and a more efficient and satisfying experience.
Development of a novel algorithm to identify staging and lines of therapy for bladder cancer.
Authors: Cary Clint , Roberts Anna , Church Abby K , Eckert George , Ouyang Fangqian , He Jinghua , Haggstrom David A
Published: September 2018

e18235

Background: Large automated electronic medical record (EMR) databases have the potential to be valuable tools in studying the patterns and effectiveness of treatment. Therefore, the current study sought to develop novel tools to identify bladder cancer cases, their clinical stage, and the chemotherapy they receive in electronic medical records. Methods: EMR data were obtained from Indiana University Health hospitals from 2008 to 2015. We developed 2 novel algorithms using natural language processing on unstructured data to identify (a) bladder cancer cases and clinical stage, and (b) chemotherapy names and line of chemotherapy. Performance characteristics for each algorithm were assessed using sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Each algorithm’s performance for case ascertainment was measured against the gold standard of manual chart review. Results: A total of 2,559 unique bladder cancer patients were identified and stratified using the clinical staging algorithm, defined as metastatic, muscle invasive, or non-muscle invasive. We identified 657 metastatic cases, 567 muscle invasive cases, and 604 non-muscle invasive cases. Next, the treatment algorithm was applied to metastatic patients to identify the type of chemotherapy received and 1st or 2nd line of therapy. The sensitivity, specificity, PPV, and NPV for the clinical staging and treatment algorithm were calculated against the gold standard of manual chart review (Table). Conclusions: The performance of the staging algorithm demonstrates the strength of using innovative approaches. The poor performance of the treatment algorithm sets a framework from which to build upon in future work and suggests that structured approaches may still be the preferable approach. [Table: see text]
Bevacizumab-induced bleeding in colorectal and noncolorectal cancer patients in a community oncology setting: An Abington Memorial Hospital experience.
Authors: Ali Naveed , Malik Faizan , Naglak Mary , Jafri Syed Imran Mustafa , Fidler Christian , Shahin Mark S. , Seidman Michael J. , Cohen Steven J.
Published: September 2018

e18250

Background: Bevacizumab (Bev) can be associated with clinically significant bleeding. Patients (pts) in community practice have increased comorbidities, leading to some reluctance to use Bev with anticoagulation (AC) or antiplatelet therapy (APT). This study was conducted to determine the incidence of Bev induced bleeding in colorectal (CRC) and non-colorectal (non-CRC) cancer pts in a real-world setting. Methods: In this retrospective analysis, pts with Bev treated CRC and non-CRC from Jan 2010 to Jan 2017 at our hospital were identified. Bleeding was graded according to CTCAE v4.0. Chi-Square and ANOVA were used to calculate associations. Overall survival (OS) and progression free survival (PFS) were calculated using Kaplan-Meier and log rank methods. Results: 241 pts were evaluated (mean age = 63; 54% females), 112 with CRC and 129 with non-CRC (lung = 27%; gynecologic = 14%; CNS = 7%; other = 5%). Median duration of Bev therapy was 21 weeks. Overall bleeding was 22% (mucocutaneous = 14%; hematochezia = 4.5%; hematemesis = 1%; hematuria 2.5%; cerebral hemorrhage = 1%). Grade 3 bleeding occurred in 8 pts (epistaxis = 1; hematemesis = 2; hematochezia = 1; hematuria = 4), of whom 1 was on AC. There were no grade > 3 events. Concomitant AC (n = 35) increased bleeding risk ( p = 0.01) whereas APT (n = 43) did not ( p = 0.4). There was no association of bleeding and Bev dose ( p = 0.1); however, longer duration of therapy increased bleeding risk ( p = 0.01). In CRC pts, concomitant chemotherapy (oxaliplatin vs irinotecan), bleeding history, intact tumors and tumor side were not associated with increased risk ( p > 0.05). In CRC, pts with bleeding had longer estimated median OS (52 [95%CI, 35-66] vs 35 [95%CI, 22-48] months; p= 0.079) and PFS (80 [95%CI, 59-101] vs 72 [95%CI, 49-95] months; p= 0.048). Conclusions: We demonstrated in a modern community hospital practice that there is a 22% incidence of bleeding with Bev, although mostly mild even with concurrent AC, and only 3% grade 3. Concurrent AC but not APT was associated with increased bleeding risk and warrants careful discussion with pts. The observation of longer OS and PFS in pts with Bev induced bleeding warrants further investigation.
Role of nutrition in incidence and management of cancer therapy-induced diarrhea (CTID): HEAT (Health Eat and Toxicity) prospective interventional study and preliminary data.
Authors: Mirabile Aurora , Vecchio Erika , Falvella Stefania , Barbarini Lucia , Butti Chiara , Ciambelli Fabrizio , Bovio Antonella , Pauli Sergio , Ricci Isabella , Frigo Fiorenza , Del Grosso Elisabetta , Aloisio Enrica , Oliva Giovanna , Artale Salvatore Agatino
Published: September 2018

e18251

Background: Metastatic colorectal cancer (mCRC) patients (pts) are at high risk of CTID influencing treatment outcome. The primary end-point of our study was the decrease of grade 3-4 (G3-4 from Common Terminology Criteria for Adverse Events 4.0) CTID incidence to 50% in respect to literature data. A predefined nutritional regimen was planned and administrated to each pts. In explorative analyses, we investigated the correlation between Vitamin D deficiency and CTID incidence and between dihydropyrimidine dehydrogenase (DpD) mutations and CTID. Methods: All mCRC pts undergoing chemotherapy (CT) with an expected G3-4 CTID incidence of about 17% were enrolled. During CT the nutritionist administered a predefined, slag free diet according to Italian Society of Human Nutrition indications and within World Cancer Research Found recommendations. Results: Fifty consecutive pts were enrolled within 11 months. Pts characteristics are summarized in the table. A significant decrease (p-value 0.00096; IC 95% 0.059) of G3-4 CTID incidence to 95% was obtained in respect to literature data. No CT modification or admissions/supportive care were needed. Due to strict diet adherence (96%) > 50% pts had no diarrhea and no one had G4 diarrhea. BMI improved in 35% over-weights and in 40% obese, no changes in normal-weights. The correlation analysis showed the decrease of CTID incidence with the increase of vitamin D levels, but did not reveal a relation between DpD mutations and diarrhea. Conclusions: The preliminary results suggest a possible role of the diet on CTID prevention and a correlation with vitamin D levels. [Table: see text]
Satisfaction among lung cancer (LCa) patients (pts) in multidisciplinary (MDC) vs. serial care (SC) settings.
Authors: Ward Kenneth Daniel , Boateng Nana , Rugless Stewart Fedoria Elaine , Smeltzer Matthew , Jackson Bianca , Foust Courtney , Faris Nicholas Ryan , Ray Meredith , Osarogiagbon Raymond U.
Published: September 2018

e18254

Background: Coordinated MDC, in which all key specialists concurrently provide early input, develop and execute a consensus plan of care in collaboration with pts and their caregivers, may improve satisfaction with care. We rigorously evaluated this premise. Methods: Prospective clinical cohort study comparing newly-diagnosed LCa pts receiving MDC (n=156) or SC (n=307) in the same healthcare system. Pts were enrolled before treatment onset. At baseline (study entry) and 3 months later, pts and caregivers completed treatment-related measures from the Consumer Assessment of Healthcare Providers and Systems (CAHPS) survey, including perceptions of quality of care, satisfaction with care, and extent of involvement in decision making. Satisfaction indices at 3 months will be compared in multiple linear regression models, adjusting for baseline scores and demographic and treatment-related characteristics. Results: Pt characteristics were similar, except for age and stage (Table). At baseline, MDC pts rated their care more positively than SC pts, but satisfaction with provider communication was similar. Three month data are currently being analyzed. Conclusions: MDC provided greater pt satisfaction in the diagnostic phase of LCa care. Further prospective analyses will test the hypothesis that MDC pts experience greater satisfaction with quality of care and provider communication compared to SC pts. Clinical trial information: NCT02123797. [Table: see text]
What do patients really want to know?
Authors: Ahamad Anesa Waheda , Wallner Paul E. , Salenius Sharon , Ross Rudi , Fernandez Eduardo
Published: September 2018

e18261

Background: We describe and analyze the quantity, nature and spectrum of questions asked by patients at consultation for radiotherapy to clarify the volume of questions that patients have and to inform the extent to which pre-composed non-personalized educational material is sufficient. Methods: With IRB approval, we retrospectively reviewed records of consultations that were performed by a single radiation oncologist from 2012 to 2016. Patients had been asked to list all of their questions exhaustively, which were then documented. To define topics for data abstraction, questions were extracted from records of a pilot group from the initial six-month period. One hundred and seventy five questions were obtained and were condensed into 57 information topics that were further grouped in to 34 themes, nine subjects and 2 broad areas. Results: A total of 2,386 questions were posed by 396 patients. The median number of questions asked per patients was 6, range 0 to 16 and interquartile range 4. There were 878 disease-related questions (36.8% of all questions) and 1,358 radiation modality-related questions (56.9% of all questions). The frequency of questions on each of nine subjects is listed in the Table. Conclusions: It is important to elicit all patients’ questions and concerns during consultation. Since almost 40% of all questions were disease-related regarding the details of the individual’s tumor, pre-composed non-personalized educational material is not sufficient. The 3 most frequently asked subjects also cannot be adequately given as a set on non-personalized information: they require details of their individualized radiotherapy logistics, side effects and radiation technical details. Further study is needed to measure the amount of time and effort required to evaluate and manage the information needed and whether the practice of personalization of information merits additional reimbursement or coverage. [Table: see text]
Incidence of pregnancy events among women with a malignant disease diagnosis.
Authors: Rodriguez Maria Alma , Cheng Lee , DeJesus Alma Yvette , Milbourne Andrea
Published: September 2018

e18262

Background: Pregnancy concurrent with cancer is rare, but adds additional complexity to cancer management and treatment. Little information is available about incidence of pregnancy events among women with malignant diseases. We aimed to describe the incidence of pregnancy and the clinical characteristics of pregnant women with cancer who have received care at MD Anderson Cancer Center. Methods: This was an IRB-approved retrospective cohort study. We searched our electronic health records for women aged 12-50 years, with a cancer diagnosis, treated from January 1, 2011, to December 31, 2015. Results: Over 5 years, out of 30,670 unique female patients (pts), 315 (1.02%) had pregnancy events documented. The distribution of events by malignant disease site is shown in Table 1. When pregnancy was documented or diagnosed, the pts’ mean age was 31.3 years (range: 16.5-50.1) and mean gestational age was 17.8 weeks (range: 1.0-38.0). There were 18 documented terminations of pregnancy events (16 = 1st trimester; 2 = 2nd trimester). Of these pts, 83% (15/18) had received chemotherapeutic agents during 1st trimester = 11 cases; 2nd trimester = 2 cases; 12 weeks pre-conception = 2 cases. Conclusions: Most pregnant cancer pts can be safely treated. Most pregnancy terminations were associated with chemotherapy administration, prior to and within the first trimester of pregnancy. Thus, it is important to conduct pretreatment pregnancy screening and effective contraception when women of reproductive age are treated with a potentially teratogenic agent. In addition, urine pregnancy tests, recommended contraceptive methods, and menstrual history need to be documented during cancer-related therapy. [Table: see text]
The quality of life (QoL) assessment of oxaliplatin-based preoperative chemotherapy for locally advanced gastric cancer: An integration analysis of two prospective phase I study.
Authors: Satake Hironaga , Miki Akira , Yasui Hisateru , Tsuji Akihito
Published: September 2018

e18263

Background: Surgery with lymph node dissection is the primary treatment for patients with localized resectable gastric cancer. However, the prognosis of locally advanced gastric cancer is poor. One promising approach is neoadjuvant chemotherapy, however, the use of neoadjuvant chemotherapy consisting of oxaliplatin-based regimen for locally advanced gastric cancer has not been reported. Oxaliplatin-induced neurotoxicity may continue after the chemotherapy and interfere with patients’ daily activities. We conducted two prospective phase I study of oxaliplatin-based neoadjuvant chemotherapy for locally advanced gastric cancer and assessed the oxaliplatin-induced neuropathy using the FACT-Ga and FACT-GOG-Ntx assessments. Methods: We planned two cycles of oxaliplatin administration and evaluated oxaliplatin-induced neuropathy using the FACT-Ga and FACT-GOG-Ntx assessments. Patients with locally advanced gastric cancer received two cycles of neoadjuvant chemotherapy with oxaliplatin (100 or 130 mg/m2) on day 1, as well as S-1 (80 mg/m2/day, b.i.d.) or capecitabine (2000 mg/m2/day, b.i.d.) for 14 days, repeated every 3 weeks. They then underwent gastrectomy with curative D2/3 lymph-node dissection followed by adjuvant S-1 (80 mg/m2/day, b.i.d.) for one year. QoL was assessed at baseline and during treatment. Results: Twelve patients were enrolled and fully assessed the QoL. All patients were chmo-naïve and had a good performance status: median age 70y, 67% male. The mean dose intensity of delivered during the neoadjuvant chemotherapy was 96.0% for oxaliplatin. Peripheral neuropathy was observed in all patients but with no functional disorders. Median time to QoL deterioration in FACT-G and FACT-GOG-NTx was 3 weeks. There were correlation between oxaliplatin administration and QoL deterioration by the repeated-measures ANOVA. Conclusions: FACT-GOG-Ntx showed that sensory neuropathy caused a deterioration in QoL immediately after the initiation of preoperative oxaliplatin-based chemotherapy, but that QoL recovered after the neo-adjuvant chemotherapy. Clinical trial information: UMIN000015950,UMIN000015181.
Effect of nivolumab therapy on pulmonary artery.
Authors: Fournel Ludovic , ARRONDEAU Jennifer , Boudou-Rouquette Pascaline , Girault Frederique , Revel Marie-Pierre , Mansuet-Lupo Audrey , Roche Nicolas , Damotte Diane , Goldwasser Francois , Alifano Marco
Published: September 2018

e18266

Background: Nivolumab, a human antibody targeting programmed death 1 receptor, is part of the armamentarium of lung cancer. Serious treatment-related adverse effects have been reported, including pneumonitis, whose mechanism is unclear. The aim of this study was to evaluate the occurrence of subclinical or patent pulmonary hypertension in patients receiving Nivolumab for advanced lung carcinoma. Methods: Clinical and morphometric data of patients receiving Nivolumab for treatment of advanced lung carcinoma are prospectively collected in our Institution and reviewed monthly by a multidisciplinary panel. For the purposes of the study, a blinded analysis of computed tomography (CT)-scans was performed, by two radiologists, to measure pulmonary artery (PA) and ascending aorta (Ao) diameters at the level of the bifurcation. Pre- and post-treatment PA/Ao ratios were calculated. Results: There were 62 patients with mean age and body mass index of 62.3 years and 24.3 kg/m2, all current or former smokers. Main histological type of carcinomas (stage IV in all cases) was adenocarcinoma (58.1%). Mean PA (+SD) diameters (before and after 4 cycles of Nivolumab [3mg/Kg]) were 26.3 (+/-2.8) mm and 28.0 (+3.0) mm, respectively (p = 4.9*10-7). Mean Pre- and post-treatment by Nivolumab PA/Ao ratios were 0.82 (+0.09) and 0.87 (+0.11), respectively (p < 0.001). There was no significant change in CT-scan aspect of lung parenchyma. Two patients experienced acute respiratory failure at day 52 and 58 after starting of Nivolumab therapy. CT-scan ruled out pulmonary embolism, but we observed PA/Ao ratio > 1 suggesting acute pulmonary hypertension, confirmed by echocardiography. They both died despite intensive care. Even excluding these 2 patients from comparative analysis, PA diameters and PA/Ao ratios remain significantly higher after Nivolumab treatment (both p < 0.001). Conclusions: Nivolumabcan induce subclinical or symptomatic acute pulmonary hypertensionpossibly leading to fatal adverse events.
Comparative evaluation of the safety and effectiveness of rivaroxaban (riva) and enoxaparin (enox) for treatment of venous thromboembolism (VTE) in cancer patients.
Authors: Hummert Shelly E , Gilreath Jeffrey , Rodgers George M , Wilson Nathan , Stenehjem David D.
Published: September 2018

e18268

Background: The current standard for VTE management in patients with active malignancy is low molecular weight heparin (LMWH). Direct oral anticoagulants (DOACs) are convenient options, but comparative data is lacking in cancer patients. Methods: An observational cohort study was conducted to identify patients with cancer treated with either enox or riva (institutional preferences) from December 2012 to April 2015. Patients were excluded if they received prophylactic dosing of enox, prior anticoagulation, transitioned to warfarin, or received anticoagulation for less than 15 days unless they had a bleeding event. Results: A total of 182 patients were included: enox (n = 97) and riva (n = 85). Median age was 65 years at initiation for riva vs 57 years for enox, p = 0.0007. Gender was similar between groups (54% male). Fifty-three percent (n = 97) had metastatic disease and 54% (n = 99) were actively receiving chemotherapy when diagnosed with initial VTE. Sixty-five percent (n = 119) were treated for deep venous thrombosis (DVT), 19 percent (n = 35) had pulmonary embolism (PE), and 11 percent (n = 20) had both DVT and PE. More patients initiated riva for extensive VTE’s 48% vs 29% (p = 0.02). Median duration of anticoagulation was 3.1 months in the enox group and 7.1 months in the riva group (p < 0.0001). Recurrent VTE occurred in 3 patients (one on riva). Ten percent of patients (n = 10) had a bleeding event on enox compared to 15 percent on riva (n = 13, p = 0.3). Major bleeds occurred in seven percent (n = 7) in the enox group and 8 percent (n = 7) in the riva group (p = 0.4). One fatal bleed occurred with each anticoagulant. Pharmacodynamic interactions with antiplatelet agents may have contributed to 3 major bleeds (two with riva). Three percent of patients (n = 3) experienced minor symptomatic bleeds on enox compared to six (7%) on riva. Mean time to bleeding will be presented. Conclusions: Riva is a safe and effective alternative to enox for VTE management in cancer patients. Concomitant medications must be reviewed before initiation and during anticoagulant therapy to minimize drug interactions. Randomized trials are needed to directly compare LMWH to DOACs in this population.
Reliability of administrative data for evaluating quality of systemic cancer treatment.
Authors: Krzyzanowska Monika K. , Powis Melanie Lynn , Taback Nathan , Diong Christina , Enright Katherine , Booth Christopher M. , Trudeau Maureen E.
Published: September 2018

e18269

Background: There is ongoing interest in leveraging administrative data to examine quality but methodological concerns persist. We evaluated the reliability of a previously established panel of administrative data derived quality measures for systemic treatment. Methods: The cohort consisted of women diagnosed with early stage (stage I-III) breast cancer (ESBC) in Ontario, Canada, in 2010. Performance on 11 quality indicators evaluated using deterministically linked healthcare administrative databases has been reported previously. Sensitivity and specificity were examined using the chart as the gold standard. Results: The administrative cohort consisted of 6,795 women with ESBC from which a validation cohort of 705 patients was randomly selected from among patients who underwent cancer surgery at one of five hospitals chosen to balance feasibility and institutional characteristics.Sensitivity and specificity varied by indicator (Table 1). Reliability of some indicators may have been affected by suboptimal chart documentation in instances where care spanned multiple settings or the medical record was fragmented, or where the number of eligible patients for that indicator was low. Conclusions: Administrative data can be used to evaluate quality of systemic cancer therapy but understanding the reliability characteristics of individual indicators is essential to inform their appropriate use and interpretation. [Table: see text]
Factors influencing the use of thromboprophylaxis in cancer outpatients: CAT AXIS, a case-vignette study on clinical practice.
Authors: Scotte Florian , Elalamy Ismail , Mayeur Didier , Meyer Guy
Published: September 2018

e18276

Background: Data on long-term venous thromboembolism (VTE) prophylaxis in cancer outpatients remain scarce. Our objective was to describe clinical practice and to identify factors influencing the use of thromboprophylaxis. Methods: CAT AXIS was a multicenter cross-sectional study based on the completion of physician-profile questionnaires and the assessment of 10 e-mailed credible clinical scenarios of lung, colon and breast cancer by each of participants using the case-vignettes validated method. Results: A total of 224 physicians participated allowing the completion and the analysis of 2,085 reviewed case vignettes corresponding to 765, 703 and 617 fictive clinical scenarios on lung, colon and breast cancers, respectively. The overall rate of thromboprophylaxis was 680/2085 (32.6%) among participants with a comparable proportion for the three types of cancer. Low-molecular-weight heparin (LMWH) was the most frequently used, by 92.7%, 93.8% and 83.9% of participants for lung, colon and breast cancer, respectively; treatment duration of ≥ 3 months was prescribed by 74.4% of participants. Multivariate analysis of factors influencing thromboprophylaxis based on patient’s characteristics is summarized in the table. Conclusions: In the absence of clear guidance, the use of thromboprophylaxis remains low and rather empiric even though the selection of LMWH by the majority of participants and treatment duration seems appropriate based on available data to date. ECOG index, metastatic malignancy, chemotherapy and history of thrombosis were significantly associated with the decision to use thromboprophylaxis in most situations. [Table: see text]
Incidence of peripheral neuropathy in patients with colorectal cancer receiving oxaliplatin alone vs. radiation therapy and oxaliplatin.
Authors: Lockwood Matthew Blake , Joshi Krishna Prasad , Mobley James , Sampath Suneetha , Siegel Eric R , Govindarajan Rangaswamy
Published: September 2018

e18281

Background: Peripheral sensory neuropathy (PN) is a known dose limiting toxicity of oxaliplatin, used to treat patients with colorectal cancer. Patients with rectal cancer receive radiation therapy (RT) in addition to oxaliplatin in adjuvant setting. Pelvic radiation causes plexopathy due to demyelination, ischemia due to blood-vessel injury, and nerve fibrosis. To assess if RT increases the incidence of peripheral neuropathy, we conducted an analysis of patients with colorectal cancer treated with oxaliplatin alone vs. oxaliplatin and radiation. Methods: A retrospective analysis of subjects with stages II, III, and IV rectal (R) and colon (C) cancer from 2005 to 2014 was conducted. Only subjects receiving O with or without RT were included. The incidence of PN was compared for increase in subjects receiving both O and RT compared to O alone via one-sided chi-square tests at 5% alpha, both overall and after subgrouping by stage. Results: Out of 261 subjects analyzed, 158 met the study’s criteria. There were 97 C (all received only O) and 61 R (10 received only O; 51 received O+RT). PN occurred in 37% (19/51) of subjects receiving O+RT compared to 22% (24/107) receiving only O ( P= 0.025). In Stage II-III disease, PN occurred at nearly equal rates of 36% (14/39) in subjects receiving O+RT and 33% (16/46) in subjects receiving O only ( P= 0.457). However, in Stage IV disease, PN occurred in 42% (5/12) of subjects receiving O+RT compared to 13% (8/61) of subjects receiving only O ( P= 0.009). Conclusions: In our study, the incidence of PN was higher in subjects receiving both RT and O compared to O alone. Although our study did not show higher PN in stages II and III disease, patients with rectal cancer may have residual neurotoxicity from previous radiation and the subsequent exposure to oxaliplatin may be contributing to the cumulative toxicity. [Table: see text]
Short and long term impact of financial toxicity on quality of life in the Carolina Breast Cancer study.
Authors: Spencer Jennifer , Reeder-Hayes Katherine Elizabeth , Pinheiro Laura C , Carey Lisa A. , Olshan Andrew F , Wheeler Stephanie B.
Published: September 2018

e18299

Background: High cancer treatment costs are associated with considerable distress and worse outcomes in cancer patients, a phenomenon known as “financial toxicity”. We examined changes in health-related quality of life (HRQoL) among women experiencing financial toxicity after cancer diagnosis compared to cancer patients without financial toxicity in a racially diverse cohort of breast cancer patients. Methods: HRQoL was self-reported at approximately 5 and 25 months post-diagnosis using the Functional Assessment of Cancer Treatment (FACT-G) in a prospective, population-based, cohort study with oversampling of Black and young (<50 years old) women. Women reported on the financial burden of their breast cancer, including whether they had declined or delayed care due to cost or transportation barriers and whether they lost a job, experienced a reduction in household income, or lost insurance coverage after their cancer diagnosis. We assessed changes in HRQoL from 5 to 25 months according to financial toxicity experience. Results: 2,432 women completed 5- and 25-month HRQoL surveys and were included in analyses. Forty-nine percent were non-Hispanic Black and 51% were non-Hispanic White; other minorities were excluded due to small numbers. Overall, 49% of women reported at least one indicator of financial toxicity (59% Black vs. 39% White). Women who reported any financial toxicity had significantly lower scores on the FACT-G at baseline (75.5 vs 87.2, p<0.001) and reported significantly less improvement in HRQoL from 5- to 25-months than women who did not report financial toxicity (incremental difference: +1.4 vs +3.8, p=.01). Black women reported lower overall HRQoL than White women (p=0.03), but impact of financial toxicity on HRQOL was similar among black and white women in stratified analyses. Conclusions: Financial toxicity is associated with lower HRQoL and with less improvement in HRQoL in the two years following breast cancer diagnosis. [Table: see text]
Acute care reliance among patients with advanced cancer with or without nurse navigation.
Authors: Kowalkowski Marc , Blackley Kris , Farhangfar Carol J.
Published: September 2018

e18303

Background: Acute care utilization is a key component of health care cost among oncology patients, particularly at advanced stages. Oncology nurse navigation (NN) was developed to improve access to quality cancer care but little is known about the impact of NN on acute care reliance (ACR) among patients with advanced cancer. Methods: A cohort study was conducted among adults (≥18) diagnosed with advanced-stage (III/IV) first primary solid tumor (10 most common solid tumors by annual incidence - bladder, breast, colon, kidney, lung, melanoma, pancreas, prostate, thyroid, uterus) from January 2013-December 2015. For inclusion, NN patients had to initiate NN services ≤30 days after diagnosis and all patients must have had ≥30 days of follow-up. The primary outcome was ACR, defined as the proportion of total health care utilization received in an acute care setting (hospital inpatient/observation, emergency department), from diagnosis through 1 year, calculated per 30-day interval to adjust for follow-up variance. To assess the effect of NN receipt on ACR, generalized linear models were fit specifying a gamma distribution and a log-link function, adjusted for patient and clinical characteristics at diagnosis. Subgroup analyses were conducted in patients surviving < 6 and ≥6 months. Results: 2950 patients with advanced cancer were followed (NN = 970 [33%]). Lung (37%), prostate (13%) and breast (12%) cancers were most common. 944 (32%) patients died during the 1-year interval. Patients averaged 1.7 health care encounters per 30-day interval. Those who received NN had lower mean ACR than patients who did not, overall (0.18 vs 0.30; p < 0.001) and in each individual cancer type (p < 0.05) except melanoma (p = 0.4). In multivariable models, NN receipt was associated with decreased ACR (RR = 0.65 95%CI = 0.60-0.70). The effect of NN on ACR was consistent in subgroups defined by survival duration. Conclusions: Patients with advanced cancer who received NN were less reliant on acute care than patients who did not receive NN. Given the role of acute care in driving health care cost and the inverse association between increased ACR and health care quality, our findings may have important implications for improving value in oncology care.
Evaluation of value in non-inferiority trials by ASCO’s conceptual framework.
Authors: Miyamoto Kenichi , Nakamura Kenichi , Fukuda Haruhiko
Published: September 2018

e18304

Background: ASCO released a conceptual framework assessing the value of cancer treatment options in 2015 and its updated version in 2016 as a tool to evaluate clinical benefit and toxicity in clinical trials. This framework was developed as a facilitator of discussions on the individual treatment between physicians and their patients. This tool consists of the elements of clinical benefit, toxicity, and symptom palliation, and these elements are combined into a score termed the net health benefit (NHB). However, in the clinical setting, not only these elements but also various factors benefit patients such as more convenient treatment schedule, shorter administration time, or non-invasive route of administration. Especially, test treatment in non-inferiority trials is likely to have these merits in addition to the benefit in toxicity. Therefore, we investigated whether the ASCO framework can identify reasonable NHB in test treatment regimens of non-inferiority trials. Methods: A systematic literature search of randomized non-inferiority trials for cancer reported from 2009 to 2015 was performed using PubMed. Inclusion criteria were English, a full-length article, available toxicity data, non-inferiority trial with a positive result, and chemotherapy. We calculated clinical benefit, toxicity score, bonus points, and NHB according to the ASCO framework. Results: We found 20 non-inferiority trials. Median sample size was 419. The common cancer types were colorectal (7 trials), lung (5), hematologic (2), and breast (2). Of 20 trials, 8 were conducted internationally, 4 in Japan, and 3 in Germany. In the ASCO framework, median NHB was 4.5 points, and 7 of 20 trials (35%) showed negative impact of test treatment, which means that NHB was minus points (-0.6 to -24.53). In 6 of these 7 trials, test treatment was in more convenient schedule or administered by non-invasive route compared with standard treatment. Conclusions: In the ASCO framework, merits in treatment schedule or route of administration may not be fully captured, and the test treatments in some non-inferiority trials showed negative NHB. It is desirable to assess not only NHB but also such merits in considering the risk-benefit balance in non-inferiority trials.
Expanding indications of existing drugs and associated costs under risk reimbursement models.
Authors: Page Ray D. , Ellis Peter G. , Lokay Kathleen , Barry Amanda
Published: September 2018

e18306

Background: New payment models in oncology will likely include taking risk on drug costs. While new drugs could be excluded, existing drugs with expanded indications are problematic as the payer has limited data needed to exclude these costs. Recent label expansion for pembrolizumab (PB) in 1st line NSCLC for > 50% PD-L1 expression is an example of this risk. A broader indication in the future will likely result in use of PB for almost all 1stline patients. Methods: We reviewed treatment starts documented by providers in the Via Portal (VP) for 1st, maintenance (MT) and 2nd lines of therapy in non-squamous mutation-negative NSCLC for the 12 months ended 11/30/16. We assumed 6 month treatment lengths and calculated cost to Medicare (MC). We calculated a hypothetical alternative where PB received full 1st line and maintenance indication given with pemetrexed (PM) and carboplatin (per recent FDA filing and results of KEYNOTE-021 trial1). We assumed 2nd line patients received either docetaxel or ramucirumab/docetaxel (using 3rd line treatments in VP). Results: Total MC cost in the actual arm (n = 208) was $13,943,412, $12,190,264 and $11,614,488 for 1st, MT and 2nd line, respectively. The total MC cost in the hypothetical arm (n = 208) was $25,477,452, $25,687,168 and $6,415,575 for 1st, MT and 2ndline, respectively. This represents a total increase of $19,832,031 (52.5%) or $95,346 per patient. Conclusions: Bundled rates and shared savings that include oncology drugs are subject to significant financial risk for providers when existing drugs receive expanded indications to a new, larger population of patients. Langer CJ, et al. Carboplatin and pemetrexed with or without pembrolizumab for advanced, non-squamous non-small-cell lung cancer: a randomised, phase 2 cohort of the open-label KEYNOTE-021 study. Lancet Oncol. 2016;17(11):1497-1508.
Economic aspects of nivolumab in non-small cell lung cancer (NSCLC): Lessons from real life.
Authors: Dudnik Elizabeth , Roisman Laila , Bar Jair , Peled Nir , Hammerman Ariel , Daher Sameh , Moskovitz Mor Tal , Shamai Sivan , Hanovich Ekaterina , Zer Alona , Merimsky Ofer , Wollner Mira ,   Israeli Lung Cancer Group
Published: September 2018

e18322

Background: Novel immunotherapy agents' costs have a significant impact on healthcare system budgets. Aside from the cost per dose of the compound, the total treatment cost (TTC) is affected by the duration of treatment (DOT). DOT in real life may differ significantly from that observed in the randomized clinical trials because of the differences in baseline patient characteristics and treatment patterns. Methods: Advanced NSCLC patients (pts) (n=192) treated with nivolumab 3mg/kg q2w (expanded access program/standard of care) at five Israeli cancer centers between January 2015 and March 2016 were included in the analysis. DOT and TTC were assessed in 2 groups (group A: ECOG PS 0/1, n=92; group B: ECOG PS ≥2, n=100). In addition, response for a subgroup of 49 pts was evaluated by RECIST, v.1.1. In this subgroup, DOT and TTC of treatment (Tx) beyond progression (PD) were assessed as well. Nivolumab cost per dose was calculated for a 78 kg pt based on current market price in Israel: 3 mg/kg X 78 kg = 240 mg = 11,250 NIS (2,993 USD). Results: Pt baseline characteristics: median age 67y (range, 41-99); males 68%; smokers 77%; ECOG PS ≥2 52%; Non-squamous/Squamous/NA 78%/19%/3%. 27% of pts continued nivolumab at the time of last follow-up. DOT and TTC are presented in the table below. Conclusions: DOT and TTC are similar for ECOG PS 0/1 and ECOG PS ≥2 pts. Tx beyond PD increases the TTC by 32%. These facts should be taken into consideration when evaluating budget impact of novel immunotherapy agents' implementation into routine practice. [Table: see text]
Nivolumab in the treatment of metastatic renal cell carcinoma: A cost-utility analysis.
Authors: Raphael Jacques , Sun Zhuolu , Bjarnason Georg A. , Sander Beate , Naimark David M
Published: September 2018

e18331

Background: Nivolumab was recently shown to improve overall survival (OS) and health-related quality of life compared to Everolimus in metastatic renal cell carcinoma (mRCC) patients previously treated with antiangiogenic therapies (CheckMate-025 trial). The aim of this study is to assess the cost-utility of Nivolumab versus Everolimus from the perspective of the Canadian publicly funded healthcare system. Methods: To evaluate the cost-utility of Nivolumab versus Everolimus, a Markov cohort model that incorporated data from the phase 3 CheckMate-025 trial and other sources was developed. The outcomes of interest were healthcare costs, life-months and quality-adjusted life-months (QALMs) gained with Nivolumab as well as the incremental cost-effectiveness ratio (ICER), and the incremental net monetary benefit. A lifetime time horizon was used in the base case with costs and outcomes discounted 5% annually. The probabilities of progression and death from cancer and utility values were captured from the CheckMate-025 trial. Expected costs were based on Ontario fees and other sources. Scenario and sensitivity analyses (SAs) were conducted to assess uncertainty. Results: Compared to Everolimus, treatment with Nivolumab provided an additional 3.9 QALMs at an incremental cost of 33,386 Canadian dollars (CAD). The resulting ICER was 8,608CAD per QALM gained. With a willingness-to-pay (WTP) of 50,000CAD per Quality-adjusted life-year (QALY) ( = 4,167CAD per QALM), Nivolumab was not cost-effective in the base case. In one-way SAs, Nivolumab cost, median OS and treatment duration on Nivolumab were sensitive to changes with plausible threshold values. Assuming a WTP of 100,000CAD per QALY ( = 8,334CAD per QALM) and a scenario of Nivolumab cost with no drug wastage, Nivolumab became a cost-effective strategy with an ICER of 7,881CAD per QALM. Conclusions: With its current price , Nivolumab is unlikely to be cost-effective compared with Everolimus for previously treated mRCC patients from a Canadian healthcare payer perspective. While mRCC patients derive a meaningful clinical benefit from Nivolumab, considerations should be given to reduce drug wastage and increase the WTP threshold to render this strategy more affordable.
Risk-adjustment models for breast, lung, and colorectal cancer cost, utilization, and outcomes in a commercially insured population.
Authors: Sagar Bhuvana , Lin Yu Shen , Castel Liana Desharnais
Published: September 2018

e18340

Background: Advances in oncology have led to rising costs which are unsustainable, necessitating value-based arrangements that maximize quality and overall outcomes. Our objective was to identify clinical and patient factors that predict higher costs and utilization among breast, lung, and colorectal cancer in a commercial population. Methods: We conducted a longitudinal analysis of claims in a sample of 9,748 commercially insured patients with breast, lung, and colorectal cancer, to measure costs and utilization based on presence of metastases, proxies for clinical biomarkers, patient demographics, and treatments. Results: Episode Risk Group (ERG) risk score, metastasis, and facility provider affiliation were cost drivers for all three types of cancer (breast, lung, and colorectal). Hypertension and younger age were cost drivers for breast cancer. In addition, HER2 positive status (β = 68,946, SE = 2,104, p < .0001) was significant in breast cancer, and VEGF in both lung (β = 56,975, SE = 10,138, p < .0001) and colorectal (β = 24,400, SE = 5,671, p < .0001) cancers. Metastasis also was associated with greater hospital admissions and hospital length of stay in all three cancers. Chemotherapy and supportive drug therapies accounted for the highest proportions of total medical costs among beneficiaries observed. Conclusions: Value-based reimbursement models in oncology should appropriately risk adjust by accounting for key cost drivers. Although claims-based methodologies may be further augmented with clinical data, we recommend adjusting for the factors we identified in models to predict costs and outcomes in breast, lung, and colorectal cancers.
Overall survival (OS) and stem cell transplant (SCT) in patients with FLT3 mutations treated with CPX-351 versus 7+3: Subgroup analysis of a phase III study of older adults with newly diagnosed, high-risk acute myeloid leukemia (AML).
Authors: Medeiros Bruno C. , Hogge Donna , Newell Laura F. , Bixby Dale L. , Solomon Scott R. , Strickland Stephen Anthony , Lin Tara L. , Erba Harry Paul , Powell Bayard L. , Podoltsev Nikolai Alexandrovich , Ryan Robert , Chiarella Michael , Louie Arthur , Lancet Jeffrey E.
Published: September 2018

e18507

Background: FLT3+ AML patients (pts; 20%-30% of AML pts) often have rapid post-induction relapse, highlighting the need for therapies that improve the bridge to SCT. CPX-351 is a liposomal formulation that delivers a synergistic 5:1 molar ratio of cytarabine (C) and daunorubicin (D). CPX-351 demonstrated efficacy versus 7+3 in a randomized, open-label, controlled phase III trial in pts aged 60-75 years with newly diagnosed, high-risk AML; our analysis investigated outcomes in the subset of FLT3+ pts. Methods: Pts were randomized 1:1 to induction with 1-2 cycles of CPX-351 (100 u/m2 [C 100 mg/m2 + D 44 mg/m2] on Days 1, 3, and 5 [2nd induction: Days 1 and 3]) or 7+3 (C 100 mg/m2/day x 7 days [2nd induction: x 5 days] + D 60 mg/m2on Days 1, 2, and 3 [2nd induction: Days 1 and 2]). Pts with complete remission (CR) or CR with incomplete platelet or neutrophil recovery (CRi) could receive up to 2 consolidation cycles. Results: Of the pts who had FLT3 mutations assessed and received study treatment, 22/138 (16%) pts in the CPX-351 arm and 20/136 (15%) pts in the 7+3 arm had baseline FLT3 mutations. AML subtypes in FLT3+ pts were: tAML (19%); AML after MDS with (38%) or without (10%) prior hypomethylating agents; AML after CMMoL (12%); and de novo AML with MDS karyotype (21%). In FLT3+ pts, median OS was longer with CPX-351 (10.25 mo) versus 7+3 (4.55 mo; HR = 0.57 [95% CI: 0.24, 1.33]; P= 0.093) and the rate of CR+CRi was higher (68% vs 25%). A greater number of FLT3+ pts treated with CPX-351 were able to undergo SCT (n = 10/22 [45%]; 4 pts were alive as of this analysis, after a median post-SCT follow up of 692 days [range: 96-769]) compared with 7+3 (n = 2/20 [10%]; neither pt still alive). The on-study safety profile of CPX-351 in FLT3+ pts was comparable to 7+3 and consistent with the overall study population. Serious adverse events were experienced by 7 (32%) FLT3+ pts in the CPX-351 arm and 10 (50%) in the 7+3 arm. Conclusions: CPX-351 demonstrated numerical improvement in median OS in older pts with newly diagnosed, FLT3+ high-risk AML and allowed more pts to undergo SCT. The analysis was limited by small number of pts. Clinical trial information: NCT01696084.
Real world patient numbers for AML targeted therapies.
Authors: dos Santos Marcos Tadeu , Smart Dave , Aita Eloise , Krein Peter Mark , Clark Jordan
Published: September 2018

e18510

Background: The standard of care for AML patients (pts) has not changed in 40 yrs. Molecular biomarkers FLT3 and IDH1/2 are being tested for prognosis and risk stratification and recent trial results show these will be effective for targeted therapies. We analyzed real world data from a leading clinical lab (BioReference Laboratories Inc) to evaluate the frequency of pts eligible for FLT3 and IDH therapies. Methods: FLT3 (ITD/TKD), IDH1 and IDH2 mutation status results from 384 AML patients from Mar 2015 - Dec 2016, tested by a validated NGS assay, OnkoSight™, were analyzed and frequencies compared with the literature. Results: Of 384 AML pts from 31 US States, 52 were FLT3+ (13.5%, expected (exp) 24-38%). We observed 41 IDH+ pts (10.7%, exp 8-18%), with 27 pts IDH2+ (7%, exp 8-9%) and 13 pts IDH1+ (3.4%, exp 9%). Mutations in both FLT3 and IDH were found in 10 pts (2.6% of AML pts, exp 9%). This equates to 19.2% of FLT3+ pts (exp 31%), 15.4% of IDH2+ pts (exp 26%) and 1.9% of IDH1+ pts (exp 5%). We identified 1 pt harboring an unexpected triple positive (FLT3, IDH1 & 2) as IDH1 and 2 are considered mutually exclusive. Medicare was the single biggest payer (42%). Tests were requested by community based physicians in 92% of cases. Conclusions: The data suggest fewer pts may be eligible for FLT3 and IDH therapies in a real world setting than expected from the literature, possibly due to published data usually coming from cohorts of well characterized, filtered AML pts from research projects and/or clinical trials, which may not represent routine clinical testing. We find a lower level of FTL3 and IDH mutation overlap showing approx only 3% of all AML pts as eligible for at least two options of targeted therapies (exp 9%). [Table: see text]