bluuebunny/crossref_metadata_2025 huggingface dataset:
CLO19-025: Treatment Discontinuation Due to Adverse Events and the Risk of Gastrointestinal Toxicities in Patients With Hematologic Malignancies Treated With Ibrutinib
Authors: Arevalo Meily , Zaw Myo H. , Sultan Anita , Swarup Sriman , Yee Nay N. , Thein Wai L. , Zin Myet M. , Jahan Nusrat , Thein Kyaw Z.
Published: March 2019

Background: Ibrutinib targets Bruton’s tyrosine kinase, a kinase involved in signaling of B-cell and chemokine receptors, which are implicated in the pathogenesis of hematologic malignancies. Ibrutinib has been shown to improve survival in hematologic malignancies, and yet the tolerability has not been elucidated. We undertook systematic review and pooled analysis of randomized controlled trials (RTCs) to determine the risk of gastrointestinal toxicities and the rate of treatment discontinuation due to adverse events. Methods: We performed a comprehensive literature search using MEDLINE, EMBASE databases and meeting abstracts through September 2018. Phase 3 RCTs that mention gastrointestinal toxicities and the rate of treatment discontinuation due to adverse events were incorporated in the analysis. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio with 95% CI. Random effects model was applied. Results: 6 phase III RCTs with a total of 1,811 patients with chronic lymphocytic leukemia/small lymphocytic lymphoma, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia were included. Studies comparing ibrutinib vs ofatumumab, ibrutinib vs chlorambucil, ibrutinib + bendamustine + rituximab vs placebo + bendamustine + rituximab, ibrutinib vs temsirolimus, and ibrutinib vs rituximab were included in the analysis. The incidence of treatment discontinuation due to adverse events was 9.30% in the ibrutinib group vs 13.13% in the control arm. The relative risk (RR) for treatment discontinuation was 0.740 (95% CI: 0.385–1.423; P=.367). The pooled RR of all-grade side effects were as follows: diarrhea, 1.955 (95% CI: 1.304–2.933; P=.001); nausea, 1.038 (95% CI: 0.702–1.534; P=.852); vomiting, 1.048 (95% CI: 0.547–2.007; P=.888); and stomatitis, 1.262 (95% CI: 0.112–14.173; P=.850). The RR of high-grade adverse effects were as follows: diarrhea, 1.749 (95% CI: 0.866–3.530; P=.119); nausea, 2.237 (95% CI: 0.478–10.471; P=.306); vomiting, 0.429 (95% CI: 0.111–1.659; P=.220); and stomatitis, 0.309 (95% CI: 0.028–3.440; P=.340). Conclusion: Our study demonstrated that patients on ibrutinib arm noted increased risk of all-grade diarrhea. Nevertheless, other GI toxicities as well as treatment discontinuation due to adverse events were not statistically significant in the ibrutinib group compared with the control arm.
QIM19-125: Nonclinical Needs of Cancer Patients in Spain Under Different Perspectives: A Comparative Study
Authors: Cruz Juan Jesús , Martin Isabel Ruiz , Fernandez Ana , Martín Rosana , Aranda Enrique , Carrato Alfredo , Díaz-Rubio Eduardo , Guillem Vicente , López Rafael , Feyoo Margarita , Gonzalez-Garcia Nerea , Nieto-Librero Ana , Ferrer Ramón , Gonzalo Alicia , Camps Carlos
Published: March 2019

Background: Patients with cancer and their caregivers express unmet needs beyond the clinical approach to cancer. The ECO Foundation (Quality and Excellence in Oncology) and the Spanish Association Against Cancer (AECC) have promoted a qualitative research study with the objective to identify and compare the perceptions of newly diagnosed and 2–3 years after diagnosis cancer patients, caregivers, oncologists, nurses, and social workers in relation to a set of nonclinical needs expressed by cancer patients and caregivers, and to obtain concrete and feasible proposals for improvement aimed at satisfying these needs. Methods: A multidisciplinary group of experts developed a questionnaire about information processes for cancer patients and caregivers, shared decision-making, satisfaction with healthcare circuits, the architecture of consultations, psychological support, support of associations, and the received support of hospital social workers. 14 Medical Oncology Services of Spanish hospitals have participated in this study collecting opinions from the study groups. 310 forms were collected, and data were statistically analyzed using Fisher's exact test. Results: Information processes: The opportunity to have a second opinion is positively valuated for 72.6% of patients and 70.2% of caregivers. However, although 62.5% of oncologists referred to offer this option to their patients, only 10.9% of patients reported having received it. Shared decision-making: For 58% of oncologists, patients are sufficiently trained to share decision-making, but only 24.6% of newly diagnosed patients consider being prepared. In addition, although 95.8% of oncologists report offering the participation of their patients in decision-making, only 45.8% of newly diagnosed patients and 64.4% of 2–3 years after diagnosis patients consider having received this opportunity. Psychological support: Psychological assistance was considered positive for 94.2% of the patients, 97.4% of the caregivers, 85.4% of the oncologists, and 97.1% of the nurses. However, only 21.3% of oncologists and 31.4% of nurses recognize offering such care to patients. Conclusions: Knowing the nonclinical needs, not only of patients and caregivers, but also from the healthcare professionals, is essential when designing health strategies that should align the perceptions of patients and healthcare professionals.
HSR19-090: Changes in Adherence to Tyrosine Kinase Inhibitor Treatment Patterns Among Patients With Chronic Myeloid Leukemia and the Impact on Costs: 2001–2017
Authors: Henk Henry J. , Winestone Lena E. , Wilkes Jennifer J. , Becker Laura , Morin Pamela , Lyman Gary H. , Chow Eric J.
Published: March 2019

Background: Chronic myeloid leukemia (CML) treatment improved considerably after introduction of oral tyrosine kinase inhibitors (TKI). As a result, the number of patients living with CML may reach 250,000 by 2040. We track changes in TKI treatment adherence since 2001 and provide an early assessment of treatment costs following the availability of second-generation TKIs and generic imatinib. Methods: A retrospective cohort from the OptumLabs Data Warehouse, which includes claims data for privately insured and Medicare Advantage (MA) enrollees in a large private U.S. health plan with medical and pharmacy benefits, was used. Patients with CML initiated TKI treatment between May 2001 and October 2016 and were continuously enrolled in the health plan 6 months prior through 12 months following TKI start. Adherence was defined by medication possession ratio (MPR1=total days’ supply of imatinib in 1st year divided by 365, 1=perfect adherence). Total health care costs include medical and prescription medication benefits. MPR1 was modeled using ordinary least squares regression. The association between MPR1 and healthcare costs was estimated using a generalized linear model specified with a gamma error distribution and a log link. Results: We identified 1,793 eligible patients. First-line TKI has changed over time (dasatinib and nilotinib represent 45% of all 2016 starts; imatinib 55%). From 2001 to 2016, adherence increased (Table 1). MPR1 was higher in men and increased with age until age ∼62 after which it declined. MPR1 was lower for patients with more comorbid conditions prior to treatment. Overall, MPR1 was inversely associated with total health care costs (medical and pharmacy) among privately insured (P<.001) but not MA enrollees. The net impact of MPR1 on total healthcare costs diminished over time (P<.001) where a 10% point decrease in MPR1 was associated with 12% and 4% lower total costs, prior to and following availability of 2nd generation TKIs, respectively. When examining medical costs only, MPR1 was inversely associated with medical costs for both privately insured (P<.001) and MA enrollees (P=.016). Conclusions: We found that adherence to TKI treatment increased over time. While imatinib is still used more frequently than other TKIs as first-line therapy, second-generation TKIs are becoming increasingly used as first-line agents. Possible cost-offsets are decreasing over time but it may be too early to formally evaluate the impact of generic imatinib.
BPI19-019: Avoidable Acute Care Use Associated With Nausea and Vomiting Among Patients Receiving Highly Emetogenic Chemotherapy or Oxaliplatin
Authors: Roeland Eric J , LeBlanc Thomas W. , Ruddy Kathryn J. , Nipp Ryan , Clark-Snow Rebecca , Wickham Rita , Binder Gary , Bailey William L. , Potluri Ravi , Schmerold Luke M. , Papademetriou Eros , Navari Rudolph M.
Published: March 2019

Background: Avoiding acute care services can improve cancer care and reduce cost. The US Centers for Medicare and Medicaid Services’ (CMS) new oncology outcome measure (OP-35) defines 30-day post-chemotherapy inpatient (IP) and/or emergency department (ED) events (IP/ED) as “potentially avoidable” if involving any of 10 toxicities, including nausea or vomiting (NV). Evidence demonstrates meaningful gaps in oncologists’ adherence to antiemetic prophylaxis guidelines for highly emetogenic chemotherapy (HEC), and that NV-related IP use costs >$10,000; yet the incidence of avoidable acute care events involving NV is not well studied. Methods: We assessed chemotherapy courses using IBM Explorys electronic health records (4Q 2012–1Q 2018). We identified rates of IP/ED ≤30 days post-chemotherapy, and OP-35 toxicities (NV, anemia, dehydration, diarrhea, fever, neutropenia, pain, pneumonia, or sepsis) by ICD-9, ICD-10, procedure codes, and CMS criteria. We evaluated cisplatin, anthracycline + cyclophosphamide (AC), carboplatin (>14 days apart, as a proxy for AUC ≥4), oxaliplatin (OX), and other non-HEC chemotherapy. We assessed guideline adherence, defined as triple prophylaxis (NK1 RA + 5HT3 RA +dexamethasone) rates at HEC initiation. Results: In 17,609 HEC and 56,624 non-HEC courses, we observed 30-day IP/ED utilization in 29% and 19% of courses, respectively (Table 1). For HEC, 76% of IP/ED use involved ≥1 of the 10 CMS toxicities, most often anemia (42%), pain (41%), dehydration (24%), and NV (24%). Rates of all-cause IP/ED, IP/ED with OP-35 toxicity, and NV-related IP/ED were consistent for HEC and OX. Gaps in triple prophylaxis were common in HEC. Conclusion: Roughly one-third of patients receiving HEC or OX experienced IP/ED events ≤30 days after chemotherapy. Three-quarters of IP/ED events involved ≥1 of 10 OP-35 toxicities linked by CMS to potentially avoidable acute care; of these, one-third involved NV. NV-associated acute care use is considerable, costly, and potentially avoidable with better adherence to antiemesis guidelines.
HSR19-084: Real-World Treatment Patterns and Clinical Outcomes in Non-Small Cell Lung Cancer Patients with EGFR Exon 20 Insertion Mutations
Authors: DerSarkissian Maral , Li Shuanglian , Galaznik Aaron , Bhak Rachel , Bocharova Iryna , Kulalert Thomas , Lin Huamao M. , Huang Hui , Duh Mei Sheng
Published: March 2019

Background: Mutations in the epidermal growth factor receptor (EGFR) gene have been identified in 10%–50% of patients with non-small cell lung cancer (NSCLC). Exon 20 insertion mutations represent about 2%–10% of this group. Reports of real world experience of NSCLC patients with EGFR exon 20 insertion mutations are limited. This study describes patient characteristics, treatment patterns, and survival outcomes of NSCLC patients with EGFR exon 20 insertions based on real world data. Methods: Flatiron Health electronic health record data, largely from community oncology practices, from January 2011–April 2018 were used for this retrospective observational study. Treatment-naïve (TN) and relapsed/refractory (RR) second-line patients diagnosed with NSCLC with EGFR exon 20 insertion mutation aged ≥18 years at treatment initiation were included. Patient characteristics were described, and Kaplan-Meier analyses were used to assess real world overall survival (rwOS) separately for TN (starting at first-line therapy) and RR (starting at second-line therapy) patients. Results: There were 128 TN and 71 RR patients identified. Median age was 66.5 and 65.0 years for TN and RR patients, respectively, and over half were female (TN: 59.4%, RR: 53.5%). Among 83 TN and 47 RR patients with known ECOG score at advanced diagnosis, most had score 0–1 (TN: 56.3%; RR: 62.0%). Central nervous system metastases were observed in 35.2% of TN and 33.8% of RR patients. While 45.3% of TN patients received any chemotherapy, approximately 20% of both TN and RR patient groups had exposure to various EGFR TKIs. Overall, median rwOS was low at 14.6 months for TN patients, and 10.1 months for RR patients. Conclusion: Real world survival of patients with EGFR exon 20 NSCLC remains poor. Treatment with any chemotherapy regimen was most commonly used followed by EGFR TKIs in TN patients, while the proportion treated with chemotherapy and EGFR TKIs was similar in RR patients. Despite limited evidence in this population, over a fifth of TN and RR patients received EGFR TKI monotherapy. This study demonstrated unmet need for improved therapeutic options in TN and RR patients with NSCLC with EGFR exon 20 insertion mutation.
BPI19-009: Late Administration of Luteinizing Hormone-Releasing Hormone (LHRH) Agonists and Testosterone Levels >50NG/DL in Prostate Cancer
Authors: Atkinson Stuart , Concepcion Raoul S. , McLane John A. , Boldt-Houle Deborah , Efstathiou Eleni
Published: March 2019

Background: Achieving and maintaining effective testosterone (T) suppression is key to treatment of advanced prostate cancer (PCa), for which LHRH agonists are standard of care. Increasing evidence suggests maintaining very low T levels to <20 ng/dL with androgen deprivation therapy (ADT) is desirable and correlates with disease-specific survival in patients with advanced PCa. Consistent drug delivery is important in providing continuous T suppression throughout the course of treatment without T rising above castrate level (T breakthrough). However, T breakthrough may occur between administrations, especially if a subsequent dose is delayed. Contributing factors to late administrations may include scheduling challenges, shortage of available appointments, and increasing number of patients. While FDA approvals for ADT drugs are based on a 28-day month, insurers may mandate full calendar months between doses for reimbursement. This study explored timeliness of subsequent LHRH agonist administrations and its relationship with T breakthrough. Methods: A retrospective review of electronic medical records from January 1, 2007 and June 30, 2016 of 85,030 LHRH agonist administrations for PCa treatment was conducted to evaluate the percentage of late subsequent dosing and impact on frequencies of T breakthrough, defined as T>50 ng/dL. Late administrations were defined as those on or after day 33, 98, 129, and 195 for 1, 3, 4, and 6 month formulations, respectively. Results: 26.9% of all subsequent LHRH agonist administrations were late: 14.4% were ≤1 week late, 3.1% were between 1–2 weeks late, and 9.4% were >2 weeks late. While only 4% of T values exceeded 50 ng/dL when doses were administered early/on time, 21% of T values exceeded 50 ng/dL when administrations were late. Conclusions: Over a quarter of subsequent administrations were defined as late, leading to >20% incidence of T values exceeding 50 ng/dL. Considering the clinical benefits of maintaining effective T suppression throughout a course of ADT, clinicians should administer treatments within approved dosing instructions, routinely monitor T levels, and consider prescribing treatments with proven efficacy through the dosing interval to maintain T at castrate levels.
CLO19-031: Immune Checkpoint Inhibitors: Optimization of Pharmacy Services in Toxicity Management
Authors: Fahey Olivia G. , Dow Elizabeth N. , Piccolo Jennifer K. , Leal Ticiana A.
Published: March 2019

Background: Use of immune checkpoint inhibitors (ICPi) in oncology continues to rapidly expand. ICPis have a unique toxicity profile and can lead to immune related adverse events (irAEs), some serious and potentially life-threatening. Early detection and appropriate treatment may limit the morbidity and mortality of irAEs and allow patients who are deriving benefit from ICPi to continue treatment. Pharmacists practicing in UW Health Carbone Cancer Center clinics are uniquely positioned to educate patients about common ICPi toxicities and ensure appropriate, early recognition and management of irAEs in collaboration with the multidisciplinary team. Methods: Within lung, melanoma, and gastrointestinal medical oncology clinics, a program was implemented involving pharmacists educating patients and families prior to the start of treatment as well as contacting patients at regular intervals to assess for any signs or symptoms of irAEs. The primary outcome is the number of patients experiencing Common Terminology Criteria for Adverse Events version 5.0 (CTCAE) grade 1 or 2 irAEs identified by a pharmacist enrolled in the program. Secondary outcomes include grade ≥ 3 irAEs identified by a pharmacist, the total number of patients enrolled in the program with any irAE, reason for discontinuation of ICPi, emergency department visits, and hospital admissions during the study period. Results: Between November 14, 2017 and October 15, 2018, a total of 81 patients were enrolled in the program with 49 of those patients still enrolled at the end of the study period. These patients experienced a total of 39 grade 1 and 13 grade 2 irAEs, of which 53.8% (n=28) were identified by pharmacists. The most common grade 1 or 2 toxicities identified by pharmacists were gastrointestinal (n=15) and dermatologic (n=6). Endocrine (n=7) and dermatologic (n=7) were the most common grade 1 or 2 irAEs identified by other providers. There were 4 grade 3 irAEs (endocrine, fatigue, liver, and pneumonitis) identified by other providers, and there were no grade 4 irAEs. Conclusion: Proactive pharmacist contact at regular intervals during ICPi treatment resulted in the early discovery of grade 1 or 2 irAEs experienced by patients. This pharmacist-driven approach may allow for earlier treatment of any toxicities experienced after ICPi treatment and reduce the rates of serious irAEs. Current efforts are focused on expanding these services to all UW Health Carbone Cancer Center clinics.
QIM19-117: Reducing Diagnostic Delays: Impact of a Novel Cancer Diagnostic Service
Authors: Arney Luke , Leib Ryan , Schneider Louise , Kostick Cori , Kilbridge Kerry , Khorasani Ramin , Odejide Oreofe , Carter Lindsay C.
Published: March 2019

Background: Although timeliness of care was one of the aims of quality improvement in the Institute of Medicine’s 2001 “Crossing the Quality Chasm” report, a significant proportion of patients with cancer still experience delays in diagnosis and treatment. For example, in a study of 3,831 older adults diagnosed with myeloma in the United States, the median time between the first myeloma-related symptom and diagnosis was 99 days (Friese CR, Leukemia & Lymphoma 2009). Such delays are associated with substantial anxiety, poor patient-reported outcomes, and increased cost. Methods: A novel adult cancer diagnostic service (CDS) was established by the Dana-Farber/Brigham and Women’s Cancer Center in October 2017. The clinic is embedded in the Department of Medicine at the Brigham and Women’s Hospital, with the aim of expediting the cancer diagnostic work-up and treatment for clinically complex patients with symptoms concerning for cancer, but for whom the next diagnostic steps are unclear. This clinic is comprised of an internist, a physician assistant, and a practice assistant. The clinic staff conduct a weekly phone conference with a multidisciplinary team—including a solid tumor oncologist, a hematologic oncologist, and a radiologist—to discuss the work-up for each patient. For every patient evaluated who receives a cancer diagnosis, we measure the diagnostic interval (days from CDS referral to diagnosis date). We define diagnosis date as the date the pathologic report is signed. We also measure the interval between CDS referral and first oncology appointment. Results: From the inception of the CDS to October 1, 2018, 221 patients were seen in the clinic and 91 (41.2%) were diagnosed with cancer. The top 3 cancer diagnoses were lymphoma (31%), gastrointestinal cancers (20%), and lung cancer (19%; Figure 1). The median number of days from CDS referral to diagnosis was 14 days (interquartile range [IQR], 10, 21; Table 1). Finally, the median time between referral to CDS and first oncology appointment was 20 days (IQR, 14, 27). Conclusion: This novel cancer diagnostic service substantially shorted the diagnostic trajectory (∼2 weeks) compared to existing literature with median diagnostic intervals often lasting more than 3 months (Friese CR, Leukemia & Lymphoma 2009). Our findings suggest that a cancer diagnostic care model, grounded in internal medicine, with engagement of oncologists and radiologists, has significant potential to improve delays in cancer diagnostic care.
CLO19-035: Safety Profile and Adverse Events of Sunitinib as a First-Line Treatment for Advanced/Metastatic Clear-Cell Renal Cell Carcinoma: Pooled Analysis of Randomized Controlled Trials
Authors: Haykal Tarek , Kheiri Babikir , Samji Varun , Zayed Yazan , Al-Dulaimi Ragheed , Gakhal Inderdeep , Bala Areeg , Sotzen Jason , Abdalla Ahmed , Bachuwa Ghassan
Published: March 2019

Background: Metastatic clear-cell renal cell carcinoma (RCC) is largely incurable, and its treatment remains challenging. Sunitinib, a tyrosine kinase inhibitor, is one of the current standard-of-care options for treatment-naïve patients with metastatic RCC. Despite the proven efficacy of sunitinib, prolonged treatment with some tyrosine kinase inhibitors (TKIs) has been associated with significant adverse events (AEs). Therefore, we aimed to calculate the exact prevalence of all sunitinib-related AEs in a pooled analysis from all available randomized controlled trials (RCTs). Methods: A comprehensive electronic database search was conducted for all RCTs comparing the clinical outcomes and adverse events of sunitinib versus all other available treatments for treatment-naïve advanced/metastatic clear-cell renal cell carcinoma. We then calculated the pooled prevalence of the most common reported side effects of sunitinib. All statistical analyses were performed using R Statistical Software v3.4.0 (R Foundation, Vienna, Austria). Results: We included 8 RCTs, with a total of 4,106 patients. The mean age was 62, with 66.44% males. Any grade AEs were reported in 72% of patients with the following frequencies: fatigue, 44%; diarrhea, 38%; nausea, 31%; hand-foot syndrome, 30%; hypertension, 27%; dysgeusia, 25%; hypothyroidism, 25%; cconstipation, 20%; stomatitis, 20%; inflammation of the mucosa, 18%; dyspepsia, 16%; vomiting, 14%; rash, 12%; asthenia, 11%; and epistaxis, 10%. Grade 3 (severe) AEs were reported in 52% of patients with the following frequencies: hypertension, 9%; fatigue, 8%; hand-foot syndrome, 5%; asthenia, 5%; diarrhea, 4%; and inflammation of the mucosa, 2%. Laboratory abnormalities were also reported as follows: increased AST, 7%; increased lipase, 6%; neutropenia, 6%; thrombocytopenia, 6%; hypophosphatemia, 5%; lymphocytopenia, 5%; anemia, 4%; and leukopenia, 3%. Conclusion: Despite sunitinib being one of the current standard treatments for patients with metastatic/advanced clear-cell RCC, its safety profile is concerning, with a high prevalence of reported dangerous side effects. These findings underscore the importance of the emergence of newer drugs and treatment plans for patients with metastatic RCC, not only to achieve similar or better clinical outcomes but also to decrease the burden of adverse events.
CLO19-059: A Systematic Review and Meta- Analysis of Randomized Controlled Trials to Evaluate the Risk of Health-Related Quality of Life Events in Patients With Hormone Receptor-Positive HER2-Negative Metastatic Breast Cancer Treated With CDK 4/6 Inhibitors
Authors: Yendala Rachana , Thein Kyaw , Swarup Sriman , Sultan Anita , Ball Somedeb , Quirch Miguel , Zaw Myo H. , Myat Yin M. , Jones Catherine
Published: March 2019

Background: Pain, fatigue, hot flushes, and rash significantly contribute to quality of life in breast cancer patients undergoing chemotherapy. Hormone receptor-positive breast cancer is a common entity among women worldwide. In cancer cells, CDK4/6 activity is over expressed, which can lead to amplification or overexpression of the genes encoding for CDK 4/6 or the cyclin D, ultimately leading to endocrine therapy resistance. We undertook a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of health-related quality of life (HRQOL) events associated with CDK 4/6 inhibitors. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE databases, and meeting abstracts from inception through September 2018. RTCs that mention HRQOL events as adverse effects were incorporated in the analysis. Mantel-Haenszel (MH) method was used to calculate the estimated pooled risk ratio (RR) with 95%CI. Random effects model was applied. Results: 8 RCTs (7 phase III and 1 phase II) with a total of 4,557 patients were eligible. The study arms used palbociclib/ribociclib/abemaciclib with letrozole or anastrozole or fulvestrant or other hormonal agent while the control arms utilized placebo in combination with letrozole or anastrozole or fulvestrant or other hormonal agent. The RR of all-grade side effects were as follows: fatigue, 1.226 (95% CI: 1.079–1.393; P=.002); back pain, 0.971 (95% CI: 0.844–1.117; P=.681); arthralgia, 0.978 (95% CI: 0.830–1.152; P=.790); headache, 1.046 (95% CI: 0.928–1.179; P=.459); alopecia, 2.635 (95% CI: 1.966–3.533; P<.001); hot flushes, 0.901 (95% CI: 0.766–1.060; P=.210); and rash, 2.068 (95% CI: 1.604–2.666; P<.001). The RR of high-grade side effects were as follows: fatigue, 3.487 (95% CI: 1.765–6.889; P<.001); back pain, 1.364 (95% CI: 0.695–2.679; P=.367); arthralgia, 1.148 (95% CI: 0.509–2.593; P=.740); headache, 0.807 (95% CI: 0.303–2.147; P=.667); and rash, 3.018(95% CI: 0.954–9.554; P=.060). Conclusions: Our study showed that the risk of developing all grades of fatigue and any-grade alopecia and rash was significantly with CDK 4/6 inhibitors. Prompt intervention with good supportive care is required.
EPR19-070: Incidence Pattern of Malignant Lymphoma by Cell-Lineage/Cell-Maturity Status in Nagasaki, Japan, 1985–2012: Preliminary Results
Authors: Hanh Luong Thi My , Niino Daisuke , Kondo Hisayoshi , Miura Shiro , Nakashima Masahiro , Iwanaga Masako
Published: March 2019

Background: Malignant lymphoma (ML) is a heterogeneous neoplasm with a wide range of etiological factors, pathological patterns, incidence rates, and outcomes. Most epidemiological studies have reported the incidence pattern of ML by simply dividing into 2 groups, Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL). However, differences in the incidence pattern by cell-lineage or by cell-maturity have been rarely evaluated. The aim of this study was to characterize the incidence pattern of ML by cell-lineage and cell-maturity in Japanese population. Methods: This is a descriptive study based on regional cancer registry data. We obtained a dataset of anonymized 12,645 cases with ICD-O histology codes of ML diagnosed 1960–2012 from the Nagasaki Prefectural Cancer Registry. From those, we excluded 1,477 records because of codes other than ML, diagnosed before 1985, and possible relapse records of identical cases. Records based on ICD-O-1 or ICD-O-2 were substituted by the corresponding ICD-O-3 code. We also treated patients having multiple types of MLs at same diagnosis date as a single case of “composite/discordant lymphoma,” and patients having multiple types of MLs at different diagnosis date as a single case based on the first lymphoma. We finally confirmed 11,118 patients of ML that occurred in 1985–2012. The overall age-adjusted incidence rate (per 100,000 population) during 1985–2012 was already reported to be 20.5 for men and 12.9 for women. Then we divided them into the following cell-lineage/maturity groups: precursor B (B1), mature B (B2), other B (B3), precursor T (T1), mature T/NK (T2), undetermined cell-lineage NHL (U), HL (H), and other lymphomas (O). Results: The median age at diagnosis of all patients was 69.7 years (interquartile range, 59.4–78.0 years) and male sex were 5,980 (53.8%). The frequency of B-cell lineage, T/NK-cell lineage, and Hodgkin lymphoma were 5,196 (46.7%), 3,257 (29.3%), and 209 (1.9%), respectively, with a significant sex difference (P<.0001). For B-cell maturity, B2 was predominant (84.8%), followed by B3 (14.4%) with a significant sex difference (P<.0001). In T-cell, T2 was predominant (99.4%). Conclusion: This preliminary analysis suggests a significant sex difference in the cell-lineage and cell-maturity of ML. Additional analysis to elucidate whether there are any differences in the incidence pattern by cell-lineage and by cell-maturity of ML between general population and Nagasaki atomic bomb survivors are underway.
QIM19-139: Reflex Testing of Oncotype DX Recurrence Score: A Single Institution Review of a Quality Improvement Protocol
Authors: Piltin Mara A. , Eckert Kathryn , Wight Margaret , Shienbaum Alan J. , Chiffarano Jeanine , Poretta Trina A. , LaCouture Tamara A. , Khattak Monica N. , Gaguski Michele E. , Imperatore Alyssa , Golthi Sruti , Yoon-Flannery Kahyun
Published: March 2019

Background: Implementation of genomic assays has led to treatment of early-stage breast cancers with high risk of recurrence with adjuvant systemic chemotherapy while sparing those with a low risk of recurrence from systemic therapy with minimal benefit. Genomic assays are becoming a more widely used tool, evident by the eighth edition of the American Joint Committee on Cancer (AJCC) Breast Cancer Staging System, which includes recurrence score as part of the treatment algorithm in certain subgroups of tumors. Our institution identified the time to assay result as a quality improvement opportunity. We instituted a protocol to have a reflex testing of Oncotype DX based on certain criteria to decrease time to assay results and ultimately time to treatment. Methods: Our Multidisciplinary Breast Leadership Committee instituted a policy for reflex Oncotype DX testing on patients under the age of 70 with estrogen receptor positive, HER2-neu protein–negative, and node-negative invasive breast cancers measuring between 0.5 cm to 5 cm in January 2018. We compared our data available from pre- and postimplementation using the single factor analysis of variance (ANOVA) as well as an independent t-test and a post-hoc Tukey-Kramer test. Results: We have observed 45 cases that met the criteria for reflex Oncotype Dx testing since the initiation of this quality improvement protocol. The recurrence scores ranged from 0 to 55. There was a statistically significant difference in the number of days from operation to result day from 2016 to 2018 (55 days vs 18 days; P<.001). The number of days from the test order date to result date also saw a significant improvement from 2016 to 2018 (12 vs 9 days; P<.05). Conclusions: Breast cancer treatment options continue to evolve, particularly with the use of genomic assays. Our single institution review confirms the utility of our reflex Oncotype DX protocol with a decreased time to result with reflex testing of patients in the appropriate clinical setting. Further development of similar pathways may be necessary to streamline our patients’ care in the treatment of breast cancer.
HSR19-091: Incidence of Adverse Events Following Use of Different PARP Inhibitors: Systematic Review and Meta-Analysis
Authors: Ho Thanh , Riaz Irbaz Bin , Akhter Maheen , Malik Saad Ullah , Riaz Anum , Farooq Muhammad Zain , Khan Safi U. , Wang Zhen , Murad M. Hassan , Hendrickson Andrea Wahner
Published: March 2019

Background: Poly (ADP-ribose) polymerases (PARPs) are a highly conserved family of enzymes whose main function is to preserve genomic integrity following DNA damage. PARP inhibitors (PARPi) are increasingly used in cancers with deficiencies in homologous recombination. Clinical trials in breast and ovarian cancers have led to several FDA approvals in recent years, and their use in clinical practice is continuing to rise. It is thus necessary to assess their adverse event (AE) profile. Method: Literature search was performed using Ovid MEDLINE, EMBASE, CENTRAL, and Scopus (inception through October 26, 2018). Eligible studies were phase 3, randomized, controlled trials that compared single agent PARPi to placebo or standard treatment. Number of patients treated and AEs reported were recorded. Observed incidence of AE was reported with 95% CI. Heterogeneity was evaluated using Cochran Q statistic and I2 statistics quantified the proportion of heterogeneity not due to chance. Results: Databases revealed 869 references. Of these, 6 were eligible: 2 in breast cancer (OlympiAD, EMBRACA) and 4 in ovarian cancer (NOVA, ARIEL3, SOLO1, SOLO2). PARPi included niraparib (NOVA), olaparib (OlympiAD, SOLO1, SOLO2), rucaparib (ARIEL3), and talazoparib (EMBRACA). Of 1,685 patients who received PARPi, incidence of any AE, regardless of grade, was 98.5% (95% CI, 97.2–99.2%). Common AEs were: nausea (incidence rate, 68.9% and 95% CI, 58.7%–77.5%), fatigue (56.3%, 45.3%–66.8%), anemia (46.3%, 37.2%–55.8%), vomiting (33.7%, 29.5%–38.3%), neutropenia (24.7%, 15.3%–37.4%), headache (23.9%, 19.9%–28.4%), and reduced appetite (21.7%, 19.3%–24.3%). Myeloid neoplasms were rare (1.2%, 0.7%–1.9%). Incidence of grade 3 or higher AE was 44.3% (30.2%–59.5%) and often related to myelosuppression, specifically anemia (24.7%, 15.3%–37.4%), neutropenia (10.7%, 6.6%–16.9%), and thrombocytopenia (5.0%, 1.7%–14.0%). Incidence of serious AE was 24.3% (19.4%–29.9%); dose interruption occurred in 53.3% (41.2%–65.0%) and dose reduction occurred in 39.2% (23.6%–57.4%). 10% (7.4%–13.6%) of patients discontinued therapy due to AE. Death due to AE was rare; less than 1% (0.4%, 0.2%–0.8%) in all trials. Conclusion: Myelosuppression and gastrointestinal toxicities were the most commonly reported AE in 6 randomized phase 3 trials of PARPi for breast and ovarian cancers. Therapy was rarely discontinued due to AE. It remains to be seen whether these results will be reflected in clinical practice.
QIM19-141: SOAR (Survivors Overcoming and Achieving Resilience)
Authors: Rivero Bianshly Rivera , Pflanzer Sonya , Riccardi Diane , Pabbathi Smitha R.
Published: March 2019

Background: There are 4 components of survivorship care: prevention, surveillance, interventions, and coordination between oncology and primary care/specialists. As part of the initial visit in Moffitt’s survivorship program, we provide a comprehensive and personalized care plan to our patients with a focus on wellness. We understand the transition from active treatment into the extended phase of survivorship can be fraught with many unexpected physical, emotional, psychological, and social challenges, yet this could also be a critical period where survivors are uniquely positioned to adopt healthy and resilient behaviors. We want to help patients be empowered through knowledge from interactive and multidisciplinary classes and we aim at improving their quality of life. Methods: We created an 8-week curriculum customized and designed for breast cancer survivors by experts in nutrition, social work, physical therapy, yoga, arts in medicine, and survivorship medicine with utilization technique–driven live food demonstrations. The core message of the series is further echoed and instilled by use of weekly journaling and guidance on how to practice the techniques following each class. Results: We completed one 8-week course. 15 patients were enrolled in the program; of these 9–12 participants consistently presented to the sessions. Sessions consisted in education regarding nutrition, emotional health, exercise, mindfulness, and medical management after completing cancer treatment. To further determine the impact of sessions, we are measuring change in health-related quality of life through the RAND-36 questionnaire with a precourse survey and a postcourse survey. As we continue our sessions and our patient population increases, we expect to have substantial data to report on the impact of this curriculum. Conclusions: It is estimated that there are more than 3.1 million women in the United States with history of breast cancer. Development of a multidisciplinary program focused in comprehensive care for breast cancer survivors may improve quality of life. These techniques can positively impact the transition from active treatment and position survivors to be better managers of their wellness.
HSR19-096: The Impact of New Oncology Drugs on Disability and Health Care Spending: An Assessment of Real-World Evidence
Authors: Kurzrock Razelle , Goldberg Robert , Ceacareanu Alice C. , Wintrob Zachary A. P.
Published: March 2019

Background: It is sometimes suggested that newly-approved cancer treatments have only marginal effectiveness, which raises questions concerning their cost-vs-benefit ratio. Such concerns appear at odds with the lower cancer-related hospitalization rate and improved survival. However, such cost-effectiveness analyses rely on population-based averages obtained from the analysis of clinical trial data. By failing to analyze data from longitudinal datasets, such assessments are unable to account for real-world patient conditions and treatment patterns in evaluating clinical and cost-effectiveness. Longitudinally surveyed clinical data has the potential to objectively reveal any association between patient outcomes and new cancer treatment utilization. Methods: We investigated the effect of being prescribed a higher proportion of new oncology drugs on quality of life, medical services use, and productivity measures as reported by the Medical Expenditure Panel Survey (MEPS, 1996–2015). General linear models with Taylor series variance estimation were applied. New oncology drugs were defined as cancer treatments marketed after the year 2000. Included subjects (N=16,677) had a solid or hematologic malignancy diagnosis (CCCodex 11–47) and available prescription data. Individual age and employment status were accounted for as covariates. All analyses were performed using SAS version 9.4 (Cary, NC). Results: Unadjusted regression data show that individuals using newer oncology treatments missed on average 2.5 (±0.3 SE) fewer days of work or school per year as compared to patients using older drugs (43% improved productivity, P<.0001). The effect persisted even after adjusting for the magnitude of the effect (P<.0001). Accounting for age, the use of newer drugs was, on average, associated with ∼35% fewer missed work or school days. Cancer patients using newer treatments had 0.06 (±0.01 SE) fewer hospital admissions/year compared to patients using older treatments (P<.0001) and spent less time in the emergency room (P<.0411) with ∼45% fewer hospitalizations. Patients using newer medicines also had fewer health-related visits (P<.0001). Conclusion: Analysis of longitudinal real-world evidence gives a more comprehensive and reliable view of the clinical and economic impact of new oncology treatments. Our data suggests significant reductions in lost work/school days, hospitalizations, and use of medical services in general.
CGE19-064: Patient Access to Comprehensive Genomic Profiling for Hematologic Malignancies: Analysis of the Payer Coverage Landscape and Results of Testing in 3,600 Patients
Authors: Maxwell Kristi , Severson Eric A. , Montesion Meagan , Marino Ingrid , Anhorn Rachel , Sawchyn Bethany
Published: March 2019

Comprehensive genomic profiling (CGP) for patients with advanced solid tumors is on the trajectory of becoming standard of care through incorporation into clinical practice, professional society guidelines, availability of an FDA-approved assay, and a national coverage determination from Medicare. For hematologic malignancies, the clinical utility of CGP can be diagnostic, prognostic, or predictive depending on the type of malignancy. Molecular testing has been standard of care for many years for hematologic malignancies, and payer coverage of the CGP approach must now be considered to keep pace with advances in the field of hematology-oncology. Based on American Medical Association CPT coding definitions, molecular testing for hematologic malignancies is categorized as testing for individual genes and gene panels of 5–50 genes or >50 genes. Our review of payer coverage policies from the Policy Reporter database in October 2018 demonstrated that payer coverage for >50 genes in hematologic malignancies is limited. As an example of coverage limitations, a recently updated Medicare Local Coverage Determination limits coverage to 50 genes or less. Coverage decisions such as these are being made during a time of increasing demand for an expanded approach. Data from the Foundation Medicine, Inc. database shows that as of April 2018, over 3,600 patients with AML, MDS, and MPN have undergone clinical testing with FoundationOne Heme, a CGP assay for hematologic malignancies. In an analysis of over 1,300 AML cases tested with FoundationOne Heme, 62% had an alteration that is included in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), and 91% had a clinically relevant alteration identified that could inform diagnosis, prognosis, or treatment selection. In an analysis of over 1,300 MDS cases tested, 70% had at least one clinically relevant alteration identified. In an analysis of over 200 MPN cases tested, 48% were triple negative for CALR, JAK2, and MPL, and of those triple negative cases, 55% had another clinically relevant alteration. These data demonstrate that FoundationOne Heme is a clinically important assay for patients with hematologic malignancies including AML, MDS, and MPN, and stakeholders within the system must now come together to further refine the clinical utility, improve payer coverage, and ensure patient access to this impactful testing as the field advances.
CLO19-041: Lymphatic Ligation Versus Conventional Axillary Lymph Node Dissection in Breast Cancer Patients: A Randomized Control Trial
Authors: Kuntaraksa Nawin
Published: March 2019

Objective: The primary objective was to evaluate seroma formation in a comparison between the lymphatic ligation technique and conventional axillary lymph node dissection. The secondary objective was to evaluate the factors affecting seroma formation. Materials and Methods: A randomized control trial was conducted between January 2014 and November 2017. 68 consecutive patients undergoing mastectomy with axillary lymph node dissection by one experienced surgeon. The patients were randomly sampled and assigned to Group 1 (lymphatic ligation; n=34) and Group 2 (conventional surgery; n=35). Results: 18 patients had developed seroma (26.09%) with 8 (23.53%) patients who were in the lymphatic ligation group and 10 (28.57%) patients who were in the conventional group. No statistical significance was discovered in seroma formation (P=.633), drain duration (P=.238) or total drain volume (P=.330) between the two groups. Longer operative time was statistically and significantly correlated with lymphatic ligation (P=.002). Age, BMI, total drain volume, and drain dislodgement were significant factors influencing seroma formation (P=.005, P=.002, P=.008, P=.015, respectively). Multivariate analysis showed age and BMI were significant factors influencing seroma formation (P=.008, P=.025, respectively). Conclusion: The lymphatic ligation technique could not reduce the incidence of seroma formation. Age, BMI were the factors influencing seroma formation in the patients undergoing mastectomy with axillary lymph node dissection.
CLO19-054: Initial Experience of a Newly Set-up Robotic Assisted Radical Prostatectomy Program From a Developing Country—Delineating the Learning Curve
Authors: Tyagi Shantanu , Roy Arandam , Mavuduru Ravimohan , Bora Girdhar , Aditya Narain Tushar , Mandal Arup Kumar
Published: March 2019

Background: Historically, the incidence of prostate cancer in India and in nonresident Indians is lower than that in Western populations. Our study aims to assess complications and short-term outcomes of robotic assisted radical prostatectomy (RARP) among postoperative patients from a tertiary care center of a developing country. Materials & Method: Prospective cohort/next 50 group, surgery between July 2017 to September 2018: Preoperative variables included demographic profile, MRI findings, PSA values, prostate biopsy reports including the Gleason score, erectile function assessment using the IIEF-5 questionnaire. Intraoperative variables included duration of surgery, blood loss, status of neurovascular bundles, whether could be preserved, lymph node dissection, and its extent. Postoperative variables included complications following the surgery (Clavien-Dindo classification), hospital stay, time of indwelling catheter. Follow-up data included serum PSA levels, status of urinary continence (daily urinary pad log ), and sexual function (IIEF 5 scores) at 3 months from surgery, then every 3 months. Retrospective cohort/first 50, surgery between December 2014 to 30th June 2017: Preoperative, intraoperative, and postoperative variables were recorded like in prospective cohort and were followed prospectively during study period. Results: Preoperative variables were comparable between two groups (Tables 1–3).Operative duration was significantly better in “next 50” group (mean, 236 minutes; range, 100–450 minutes) as compared to “first 50” group (mean, 350 minutes; range, 178–560 minutes, Duration of hospital stay is significantly less in “next 50” group (mean, 2.6 vs 4.5 days). Postoperative complications were also less commonly noted in “next 50” group (5% vs 14%; Table 4). Comparative postoperative erectile dysfunction rates were significantly less in “next 50” group (6% vs 36%), and though the postoperative incontinence rates were less in “next 50” group, it was found to be statistically insignificant (Table 5). Conclusion: Robotic-assisted radical prostatectomy is a safe and feasible option for the treatment of clinically localized prostate cancer. After due course of training period favorable and promising results can be replicated at a newly set robotic program.
Le carnet du lettré : objet matériel, objet mental
Authors: Minzetanu Andrei
Published: March 2019

Cette note de recherche présente très brièvement les hypothèses et les résultats d’une thèse de littérature comparée et d’un livre consacrés à l’histoire du carnet de lecture (Carnets de lecture, généalogie d’une pratique littéraire, 2016). J’essaie d’y révéler les tensions très fortes qui existent entre une dimension auctoriale du carnet et sa dimension éditoriale, et de proposer plusieurs notions issues des sciences humaines et des études littéraires (« objet », « trace », « geste de lecture », « pratique », « représentation » et « posture ») qui nous permettent de comprendre le carnet comme un objet matériel et comme un objet mental.
Des liasses de papier dont on fit un « oreiller » : le registre de l’écriture de Sei Shônagon
Authors: Lesigne-Audoly Evelyne
Published: March 2019

Les Notes de chevet (v. 1000) ont servi de source d’inspiration, au Japon comme ailleurs, pour permettre une écriture fragmentaire et discontinue, moyen d’expression spontané pour une écriture de l’intime. Pourtant, ce texte attribué à Sei Shônagon est avant tout le reflet d’une activité intellectuelle collective. Cet article présente et commente plusieurs extraits de l’oeuvre pour étayer cette affirmation.
Les « écritures confuses » d’Henri Thomas : perspectives poétique, générique, génétique
Authors: Hébert Sophie
Published: March 2019

Les carnets d’Henri Thomas développent une poétique singulière et se révèlent supports d’écriture privilégiés chez celui qui fit de la traversée de l’espace sous toutes ses formes un mode d’être-au-monde particulier. Immédiates, succinctes, frappantes, fusées poétiques destinées à éclairer leur auteur sur lui-même, les notes carnettistes d’Henri Thomas sont autant d’autobiographèmes cherchant à devenir expression quintessenciée de toute expérience de vie. L’étude des carnets manuscrits de cet auteur encore trop méconnu permet d’entrer plus avant non seulement dans les mystères de la création littéraire, mais aussi dans le processus qui mène le manuscrit à la publication.