bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk-stratified multidisciplinary ambulatory management of malignant bowel obstruction (MAMBO) program for women with advanced gynecological cancer.
Authors: Lee Yeh Chen , Lheureux Stephanie , Jivraj Nazlin , O'Brien Catherine , Laframboise Stephane , Tinker Lisa Michele , Patel Toral , Stuart-McEwan Terri , Savage Pamela , Easson Alexandra Maria , Croke Jennifer , Lau Jenny , Shlomovitz Eran , Chawla Tanya , Allard Johane , Buchanan Sarah , Ng Pamela , Karakasis Katherine , Oza Amit M.
Published: September 2018

e18024

Background: Malignant bowel obstruction (MBO) in gynecologic oncology patients is associated with poor prognosis, debilitating symptoms and compromises quality of life. Management of MBO poses a clinical challenge with prolonged hospitalization. Evidence based guidelines for surgical intervention, use of chemotherapy, total parenteral nutrition or best supportive care in this patient population is lacking. Surgical correction may improve survival in selected patients. Retrospective analysis to assess impact of MBO show variable range of MBO-related admissions up to 60 days, and is associated with significant morbidity. Methods: A risk stratified MAMBO program for gynecologic patients has been implemented at Princess Margaret Cancer Centre to define a systematic approach for MBO management and build multidisciplinary consensus for personalized treatment of our patients. The program is novel and includes a nurse-led ambulatory management algorithm with an eHealth application designed to monitor bowel symptoms. A symptom-driven classification system has been devised to objectively define risk using a MBO management algorithm. Complex MBO cases are discussed in designated MBO rounds for consensus treatment recommendation. All patients with MBO are enrolled into a prospective database. Patients undergoing surgical procedures for MBO are consented for opportunistic tissue collection for translational research. MBO patient education materials have been developed to improve awareness and encourage proactive bowel symptom management. Results: Seventy nine patients have been followed through this risk stratified MAMBO program for ambulatory care over 6 months. The MBO program integrates diet, laxatives/stool softeners and drug therapy. Designated MBO rounds are now established for complex case discussion. A prospective MBO database will evaluate treatment and patient-reported outcomes. Conclusions: Risk stratified model of care for multidisciplinary MBO program facilitates decision-making between disciplines and optimize patient care in a vulnerable population with support for ambulatory care.
Increasing the duration and efficacy of intravenous chemotherapy using a patient-centered digital education program: Navigating Cancer’s program for patients receiving pemetrexed for lung cancer.
Authors: Howard Scott C. , Yeatman Timothy Joseph , Watson Mark Layton , Lam Catherine
Published: September 2018

e18025

Background: Adherence to therapy improves survival in cancer patients. Patient education interventions have effectively improved adherence to oral drugs, but have not been studied for intravenous drugs. Methods: We assessed impact of a pemetrexed educational program for lung cancer patients from 58 oncology practices delivered from 2014-2016 via the Navigating Cancer (www.navigatingcancer.com) patient portal. After online registration, the program provided sequential messages about pemetrexed therapy and management of side effects. Access to each component of the education program was tracked and de-identified data provided to the study team for analysis. Results: Of 944 patients, 441 (47%) accessed pemetrexed-specific educational materials, and were more likely to be Caucasian (p=0.01) and to have never smoked (p=0.05). Patients who accessed educational materials received a mean of 286 days of pemetrexed versus 236 days (p<0.01); their one-year survival was 66% (SE 2.8%) versus 53% (SE 2.9%) (p<0.01). In multivariable analysis, survival was predicted by accessing education (p<0.01), but not race or smoking status (p>0.1). Conclusions: Drug-specific patient education delivered via a patient portal and email reached 47% of registered patients and was associated increased duration of therapy and improved survival. [Table: see text]
Enrolment of adolescents and young adults with cancer (AYAWC) to clinical trials at the Children’s Hospital of Eastern Ontario (CHEO).
Authors: Lum Sarah , Laforest Isabelle , Tang Kenneth , Abbott Lesleigh S.
Published: September 2018

e18043

Background: Five-year survival among AYAWC has seen less improvement than in other age groups. One hypothesized reason is low accrual to clinical trials, for which the reasons need further determination. Our objectives were to determine the enrolment of AYAWC on treatment clinical trials at CHEO, a tertiary care pediatric hospital in Ottawa, Canada and to determine barriers to enrolment of AYAWC compared to younger patients. Methods: A retrospective chart review of patients diagnosed at CHEO over 10 years from January 1, 2006 to December 31, 2015 was performed. AYAWC included 15-18 year olds, and younger patients included 0-14 year olds. Patients 18 years and older are treated at adult centers. The number of patients enrolled on an upfront treatment clinical trial was collected while those not enrolled were reviewed for documented non-enrolment reasons. Clinical trials available at CHEO during this time period were also recorded. Results: A total of 733 patients were diagnosed with 96 AYAWC and 637 younger patients. The proportion of patients enrolled on clinical trials was 19.8% (19) AYAWC and 27.3% (174) younger patients (p = 0.12). Trials were not available for 57.3% (55) of AYAWC and 53.7% (342) of younger patients for their disease type (p = 0.51). For the remaining 41 AYAWC, 46.3% were enrolled. For AYAWC not enrolled, 40.9% had a reason documented: for 22.2% a physician felt it was not in the patient’s best interest, 44.4% did not meet eligibility, 33.3% of families/patients declined. For the remaining 295 of younger patients that had trials available, 59% enrolled on a trial. For younger patients not enrolled, 25.6% had another reason documented: for 25.8% a physician felt it was not in the patient’s best interest, 45.2% did not meet trial eligibility, 25.8% of families/patients declined, 3.2% other reason. Conclusions: There were fewer AYAWC enrolled on trials compared to younger children. There were not fewer trials available for AYAWC patients than younger children. For patients not enrolled, the majority did not have an open trial available and otherwise, reasons for non-enrolment did not differ significantly between groups. Next steps could include data from local adult centers.
Impact of language on distress screening in cancer patients at an NCI-Designated Comprehensive Cancer Center.
Authors: Jones Veronica , Clark Karen L. , Warner Susanne , Rodriguez Jenny , Mortimer Joanne E. , Ferrell Betty R. , Seewaldt Victoria Louise , Kruper Laura , Loscalzo Matthew J.
Published: September 2018

e18070

Background: Psychological distress has been linked to poor outcomes among cancer patients. In 2007, the Institute of Medicine reported that distress is often unrecognized. While much is known about distress screening in English speaking populations, little is known about the provision of screening in Spanish. Methods: From 2009-2016, over 9000 solid tumor and lymphoma patients treated at an NCI CCC were prospectively administered a validated biopsychosocial distress questionnaire in their preferred language. The data was retrospectively stratified by language and Chi-square and ANOVA tests were performed to detect differences. Results: Spanish-speaking patients had the highest levels of reported distress in every category when compared to any other group. Of the 629 patients that reported Spanish as their preferred language, 400 (63.6%) took the questionnaire in Spanish (SS) with the rest taking it in English (SE). There was no difference in reported gender, marital status, education level or income between the two groups. The SS patients were younger (mean age 56 vs 60.5, P = 0.00) and reported significantly higher distress than the SE patients in every biopsychosocial domain except functional. The greatest difference was seen in “understanding treatment options” (40.1% SS vs 19% SE, p = 0.00) with a significant difference seen also in “fear of medical procedures” (38.2% SS vs 29.9% SE, p = 0.037), “finances” (66.5% SS vs 55.4% SE, p = 0.01), “finding community resources” (34.8% SS vs 26% SE, p = 0.03), “managing emotions” (40.3% SS vs 31.5% SE, p = 0.032), “needing help to coordinate care” (41% SS vs 23.4% SE, p = 0.00) and “transportation” (35.2% SS vs 21.9% SE, p = 0.001). The distress of the SE patients was more similar to that seen in the English-English patients, but was still significantly higher. Conclusions: These provocative data demonstrate distress levels are stratified by preferred language among cancer patients. Spanish speaking patients had the highest levels of reported distress but this difference was more pronounced when they were administered the questionnaire in Spanish. More studies are needed to determine culturally effective ways to identify distress in Spanish speaking populations.
The application of electronic medical records (EMRs) as a virtual comparator arm in a lung cancer clinical trial: A case study.
Authors: Patel Ketan , Ouwens Mario , Shire Norah , Khosla Sajan
Published: September 2018

e18098

Background: Single-arm and open-label clinical studies are common in oncology drug development, leading to a frequent need for contextualization of results and provision of other means of comparison for cost-effectiveness models. The utility of current approaches such as naïve comparisons, historical control benchmarking, and match-adjusted interventional controls is limited. An alternative approach is the use of routinely collected data from Electronic Medical Records (EMRs). This study sought to determine if overall survival (OS) in advanced non-small cell lung cancer patients from a clinical trial comparator arm could be replicated using EMR data. Methods: De-identified EMR-derived patient data from Flatiron Health were matched via propensity scores to Project Data Sphere clinical trial data for study NCT00457392 of sunitinib plus erlotinib versus erlotinib alone to compare overall survival outcomes. A Cox regression model stratified for dataset was used to estimate the hazard ratio and 95% confidence interval for OS. Results: The Kaplan Meier curves were comparable for the first period after start of treatment, but differed after median survival was reached, with the Flatiron dataset achieving longer median OS. This deviation was strongly associated with differences in post-erlotinib treatment options introduced between the clinical trial period and the EMR period. Splitting the Flatiron data in two, related to the period from which the data were obtained (pre- or post-2013), resulted in a better match for the period closer to the trial [HR: 1.12 (0.93,1.35), P = 0.219] than for the later period [HR: 1.23 (1.01,1.5), P = 0.039]. Conclusions: Our results demonstrate that the time period in which EMR data are collected is important when matching to trial data. EMR data can contextualize the OS benefit for single-arm or uncontrolled trials run in the same time period. Further exploration of time-varying effects on OS is warranted.
Gender and health care outcomes in patients with non-small cell lung cancer: A meta-analysis.
Authors: Torres-Roman Junior S , Flores Claudio J. , Aguilar Alfredo , Bretel Denisse , Rolfo Christian Diego , Raez Luis E. , Pinto Joseph A. , Mas Luis
Published: September 2018

e18113

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It is well known that there are differences in the outcome between genders; however the effects of the sex in the prognosis have not been previously properly defined. Our aim was to evaluate in a meta-analysis, differences in healthcare outcomes between women and men with NSCLC in terms of overall survival (OS) and progression-free survival (PFS). Methods: We searched for references of published studies of hospitalary databases indexed in PubMed/Medline. We retrieved 67 references (from 1989 to 2016), of which eleven references were eligible for data extraction. In total, 11 references were evaluable for OS. Meta-analysis for Hazard Ratios (HR) obtained from univariate and multivariate analysis were analyzed in different groups. The meta-analysis was done in the software Review Manager 5.3. Results: In total, 7 studies had information for OS univariate analysis, 7 studies for OS multivariate analysis, only, one for PFS univariate analysis and one for PFS multivariate analysis. The meta-analysis for OS univariate analysis resulted in a HR = 0.75 (P < 0.00001; 95% CI: 0.71 to 0.79) for women compared to men, although there was a high statistical heterogeneity between cohorts (P < 0.0001). In the meta-analysis for OS multivariate analysis was estimated a HR = 0.75 (P < 0.00001; 95% CI: 0.73 to 0.78), with statistical heterogeneity between cohorts (P = 0.0005). Conclusions: Our study quantified a 25%-risk reduction of death for women with NSCLC compare with male men patients with the same diagnosis.
Patient-reported outcomes from a phase 2 study of copanlisib in patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma (iNHL).
Authors: Keating Karen N. , Hiemeyer Florian , Garcia-Vargas Jose E. , Childs Barrett H. , Dreyling Martin H. , Zinzani Pier Luigi
Published: September 2018

e18123

Background: Information on the degree to which treatment of iNHL impacts health-related quality of life in terms of disease- and treatment-related symptoms is limited. Copanlisib is an investigational pan-Class I phosphatidylinositol 3-kinase (PI3K) inhibitor. In a phase II study in patients with relapsed/refractory iNHL, copanlisib treatment resulted in a high response rate and durable responses. We report here on patient-reported outcomes (PRO) from this trial (NCT01660451, part B). Methods: Patients with 4 subtypes of iNHL were eligible: follicular, marginal zone, small lymphocytic and lymphoplasmacytoid/Waldenstrӧm macroglobulinemia. Patients had to have received ≥2 prior lines of treatment, including rituximab and an alkylating agent. Copanlisib (60 mg, I.V.) was intermittently administered on days 1, 8 and 15 of a 28-day cycle. Health-related quality of life questionnaire FACT-Lym questionnaire (with focus on Total and Lymphoma subscale [FACT-LymS] and LOCF-method applied) was evaluated with Hodges-Lehmann estimate for change in median until week 16, including 95% confidence intervals. EQ-5D and visual analogue scale (EQ-5D VAS) were statistically described. All questionnaires were compiled at baseline and every other cycle in the first year of the study (aligned with radiological imaging). Results: A total of 141 iNHL patients were treated, with completed questionnaires received from 132 patients at baseline and 86 at week 16. The mean±SD (and median) for FACT-Lym LymS score at baseline was 45.27 ± 9.55 (46.5), and 47.20 ± 8.69 (49.0) at 16 weeks. The estimated change in median was +1.0 with 95% CI: [0.5; 2.5] and min: -13.0, max: 23.0, representing an improvement in lymphoma-related symptoms. Accordingly, the FACT-Lym total score was 126.59 ± 22.96 (127.5) at baseline and 127.99 ± 23.60 (130.8) at 16 weeks. Estimated change in median was 0.0 with 95% CI: [-0.5; 3.2] and min: -38.0, max 42.5. Conclusions: This study demonstrated the favorable impact of copanlisib treatment on disease-related symptoms and HRQoL in patients with relapsed/refractory iNHL.
Risks and benefits of phase I trials: Eighteen-year experience from a single institution.
Authors: Kam Audrey E. , Chaudhary Imran , Ghalib Mohammad Haroon , Shah Umang H. , Swami Umang , Kuo Dennis Yi-Shin , Hwang Caroline , Elrafei Tarek N. , Cohen Bruce , Gartrell Benjamin Adam , Kaledzi Elizabeth , Chuy Jennifer W. , Cheng Haiying , Rajdev Lakshmi , Haigentz Missak , Mani Sridhar , Goel Sanjay
Published: September 2018

e18146

Background: Phase I trials are a critical component of drug development; yet are considered non-therapeutic. This leads to recruitment barriers due to provider and patient discomfort. The largest meta-analysis of phase I studies has previously shown a response rate (RR) of 10.6%. Herein we report the results from our institution. Methods: Records of patients enrolled on phase I trials at our institution from January 1999 to December 2016 were reviewed. Recorded data included adverse events (AE); treatment related responses and deaths. Kaplan-Meier analysis and t-test were performed on the reviewed data. Results: During this period 774 patients were accrued on 64 phase I trials [43.8% cytotoxic, 45.3% biological, 6.2% both and 4.7% viral agents]. Primary cancer diagnoses included colorectal (25.2%), ovarian (17.6%), lung (7.8%), uterine (6.6%) and breast (6.1%). In total, 609 patients were evaluable for response, 41.1% had stable disease (SD) and overall RR was 7.7% (complete RR = 1.0%). Patients with overall clinical benefit (SD+response) had lower mean baseline WBC (4.83 vs 5.94 k/uL, p = 0.0008), ANC (2.92 vs 4.12 k/uL, p = 0.00007), platelets (209 vs 246 k/uL, p = 0.00007), LDH (280 vs 346 U/L, p = 0.0055) and higher serum albumin (3.97 vs 3.86 g/dL, p = 0.011) as compared to patients with progressive disease. Grade 3/4 non-hematological and hematological AE were seen in 28.5% and 19.9% patients, respectively. Treatment-related mortality was 0.8%. Patients with baseline LDH below the median (247 U/L) for the cohort had a higher median survival (312 days vs 201 days, p < 0.001, HR 0.61 95% CI 0.51-0.73). The median and mean duration on study were 56 and 87 days, respectively. Conclusions: This is one of the largest single-institution series of phase I oncology trials. Our RR of 7.7% [95% CI 5.9-10.1%] falls within the 95% CI of the RR of a majority of third line (and greater) chemotherapy regimens for solid tumors. Thus, the concept of 'non-therapeutic' nature of phase I studies needs reconsideration.
Treatment outcomes with first-line (1L) nab-Paclitaxel + gemcitabine (AG) and FOLFIRINOX (FFX) in metastatic pancreatic adenocarcinoma (mPAC).
Authors: Cartwright Thomas H. , Parisi Monika , Espirito Janet L. , Wilson Thomas , Pelletier Corey , Patel Manish , Babiker Hani M.
Published: September 2018

e18147

Background: AG and FFX have demonstrated improved overall survival (OS) compared to gemcitabine (GEM) as 1L treatment (tx) for mPAC. Limited comparative data exists on AG vs FFX. This study compared time to treatment failure (TTF), OS, and patient (pt) demographics in mPAC pts receiving 1L AG vs FFX, and evaluated outcomes by performance status (PS) in a real-world setting. Methods: This was a retrospective observational cohort study of adult pts diagnosed with stage IV mPAC treated with 1L AG, FFX, or GEM monotherapy between 04/2013 and 10/2015 with at least 3 mo follow-up, to 01/2016. We report results for AG vs FFX; AG vs GEM analysis is ongoing. Data were programmatically extracted from the iKnowMed electronic health record database of pts in The US Oncology Network. Eligibility included ≥3 doses of A (for AG) or ≥2 doses of fluorouracil (for FFX), and excluded pts on clinical trial or with other cancer diagnoses during the study period. Categorical variables were compared with chi-squared tests. TTF and OS were assessed using the Kaplan-Meier method. Results: 2,901 pts with mPAC receiving chemotherapy during the study period were initially identified. 486 total pts met all eligibility criteria, with 255 AG and 159 FFX pts. Median age was 68 and 61 yrs for AG and FFX respectively (p < .0001). ECOG PS was 0-1 in 77% of AG pts and 91% of FFX pts (p = 0.0004). Median TTF and mOS in all pts was 3.5 [95% CI 3.0-3.9] and 9.8 mo [95% CI 8.2-11.5] respectively. There was no statistical difference in mTTF or mOS for the AG vs FFX cohorts (mTTF 3.7 vs 4.3 mo, log-rank p = 0.25; and mOS 9.8 vs 11.4 mo, log-rank p = 0.38). Among pts with ECOG PS 0-1, TTF for AG vs FFX was 4.2 vs 4.3 mo respectively (log-rank p = 0.47); and OS for AG vs FFX was 12.1 vs 11.4 mo (log-rank p = 0.68). Conclusions: Although pts in the AG cohort were older and had worse PS, mTTF and mOS were not statistically different from pts in FFX. Results were similar after stratifying by PS. Limitations include the retrospective and non-randomized nature of the study. However, this represents real world outcomes where randomized data do not exist. Analysis of toxicities and resource utilization is ongoing and will aid in optimizing tx selection in these pts.
Building an oncology EMR database for outcomes research.
Authors: Kallich Joel D.
Published: September 2018

e18157

Background: Electronic medical records (EMR) are a resource affording many advantages. As structured data fields grow, unstructured data decreases, the potential number of research questions which can be addressed exponentially increases. Over many years working with oncology practices, we licensed HIPAA compliant EMRs into a common data format, resulting in a data base (DB) of over 1 million patients. Methods: We provide a historical perspective, information, and analysis of successes and challenges encountered working with this data, with suggestions for similar projects. Results: See table below. Conclusions: EMR DBs will be the big data sources for the analysis of cancer treatment in the US, including safety surveillance, quality improvement efforts and cost effectiveness research. Careful attention to previous efforts should facilitate adoption of new health information technology to the practice of medicine in oncology. [Table: see text]
Using a multi-disciplinary process-mapping approach for care plan program design.
Authors: Jones Meredith
Published: September 2018

e18203

Background: The Center for Medicare and Medicaid Innovation has challenged oncology practices to engage in practice transformation activities through participation in the Oncology Care Model (OCM). One difficult requirement of OCM is the creation of care plans inclusive of the 13 IOM components. Though OCM does not require that care plans be given to patients, true practice transformation exists not only with care plan creation, but with delivery and education to patients and caregivers. Many challenges to care plan implementation exist, starting with the lack of staff dedicated to the care planning process. Methods: Two multi-disciplinary teams representing the Medical Oncology Clinic were formed to simulate and process-map current workflow, incorporating care plan generation and delivery. First, teams process-mapped current workflows utilizing existing staff to establish a baseline. Second, teams added care planning to the baseline and determined whether existing or new staff would be needed to accomplish the OCM care plan requirements. Both teams received the same 6 care planning steps: 1. Enter patient demographics into software, 2. Give patient survey, 3. Enter clinical information in software, 4. Generate plan, 5. Print/deliver plan, and 6. Scan into EMR. Results: Both teams completed process mapping with minimal variation at baseline. However, the teams disagreed on responsible staff for each care planning step. Both teams agreed, though, that 4 out of 6 steps must be completed by RNs, NPs or Physicians. Both teams also indicated that current RN staffing levels would not accommodate capacity to add care planning responsibilities to existing positions, due to the time-consuming nature of the care planning process. Conclusions: Multi-Disciplinary teams recommended addition of RN Care Coordinator positions to oversee the care planning process. Successful implementation requires hiring adequate numbers of RN Care Coordinators that, with a reasonable caseload each, will manage the process, track patients and evaluate outcomes. Future opportunities exist to research the impact that the addition of both care plan delivery and RN Care Coordinators have on patient satisfaction and outcomes.
Advanced support for quality of life in oncology: Brazilian private and public health insurance cancer patients' point of view.
Authors: Almeida Gustavo Fernandes Godoy , Freitas Mauricio Assuero Lima de , Costa Marcela Silva , Cordeiro Rafaela Batista da Silva , Barros Filho Evandro Lopes de , Reis Gabriela Pereira Barreto dos , Santos Juliana Oliveira , Jatoba Luisa Conceicao Violet , Luna Estevao Michel Santana de , Silva Lauro Vinicius Machado da , Machado Alexandro , Barbosa Gabriel Brito , Freitas Thais Milla Franco de , Mattos Luiz Alberto Reis ,   Advanced Support for Quality-of-life in Oncology (ASQO)
Published: September 2018

e18229

Background: Cancer patients suffer from burden symptoms and adverse events which compromise quality-of-life. Early palliative care involvement of metastatic non-small cell lung cancer patients has demonstrated increased overall survival. Advanced Support for Quality-of-Life in Oncology - ASQO - addresses cancer and its treatment complications aiming a safe cure or symptom control and dignified death. Measure cancer patients' background and interest about their disease is critical for planning care. To study the point of view of cancer patients about ASQO and compare private and public Brazilian health insurance cancer patients. Methods: An interview was performed and SPSS was used to find means and rates. The protocol was approved by Federal University of Pernambuco ethics committee and all patients signed informed consent Results: 48 patients were interviewed, 28 at Hospital das Clinicas Federal University of Pernambuco and 20 at ÓNKOS Oncology. Attached tables show demographic data and patients’ background, interest and opinion. The topics on which more and less patients’ background were “Chances of cure” (85%) and “Fertility” (25%); Fertility (59%) and participation in clinical research (40%) were the subjects for which more and less patients wanted additional information; Among those patients who wanted additional information about any topic, the theme on which more and less comments were made were “Pain” (100%) and individualization of treatment (10%); Goals of treatment (89%) and fertility (41%) were the subjects that more and less patients were satisfied with the information received Conclusions: In Brazil, the majority of cancer patients don’t have the opportunity to discuss treatment goals and fertility is not widely discussed with them. This translated into highest percentage of interest in the subject and a higher degree of dissatisfaction with the information received, despite median age of 58 years in the study population. The high prevalence of uncontrolled pain reflected in 100% of responders have made additional comments, indicating a need for health professionals education to adequately manage this symptom. Clinical trial information: CAAE 50921215.8.0000.5208.
Patients' perception about difficulty of treatment with trifluridine/tipiracil and pharmaceutical care: Effectiveness and safety.
Authors: Diaz Marca , Llorente Alberto , Touris Manuel , Vidal Yolanda , Mosquera Alicia , Lopez Elena , Vazquez Maria Francisca , Sanchez Bibiana , Duran Goretti , Gonzalez-Anleo Cristina , Garcia Anais , Lopez Rafael , Lamas Maria J. , Bernardez Beatriz
Published: September 2018

e18249

Background: Trifluridine/tipiracil (TAS) is a new alternative in metastatic colorectal cancer patients (pts) previously treated with fluoropyrimidines, oxaliplatin and irinotecan. Objective:to analyze patients` perception about difficulty of dosage regimen with TAS, the effectiveness and safety. Methods: Retrospective observational study, including pts treated with TAS during expanded access in Spain. Oncology pharmacists, as integral part of cancer team, provide direct patient care medication therapy review, pharmacotherapy management, disease management, medication safety, dispense the medication and other clinical support that may lead to improved quality and clinical outcomes for cancer patient at the beginning of treatment with TAS. About perception we applied a survey with a numeric rating scale (0-10 integers) with 3 questions: difficulty of dosage at the beginning, at the end of 3rd cycle, and the relevance of the information provided by the oncology pharmacist. Variables studied: sex, age, KRAS status, treatment line, ECOG performance status (PS), dose reduction, previous chemotherapy and adverse events (AE) classified according to CTCAE v4.0. Effectiveness variable: progression-free survival (PFS). Results: 12 pts (10 men; 7 mutated KRAS) were included; median age 60.5 years (range 52-81). TAS line: 3rd line (4), ≥ 4th (8). PS 1 in 10 patients; 2 pts PS 2. Dose reduction was necessary in 41.7% pts. Currently 5 pts are still alive and in the survey they scored the dosage regimen with ≤5 points at the beginning and the same after 3 cycles. The relevance of, information provided by the oncology pharmacist was evaluated with 10 points. Effectiveness: median PFS 3.1 months (0.5-8.3), 2 pts continue on treatment ( medianfollow-up 8.1 months). Overall survival is not evaluable. Grade 3/4 hemotologic toxicities were most common (anemia 8,3%, neutropenia 25%). Conclusions: The perceived dosage difficulty is low, contrary to expectations. It is important to emphasize the evaluation of the information provided by the oncological pharmacist. Our study supports an effectiviness similar than the efficacy. Hematological is the most important and common toxicity.
Pneumocystis infection during first-line chemotherapy for solid tumours: Increased virulence or better diagnosis?
Authors: James Alena Talia , James Alex , Pinto do Nascimento Marcela , Higgs Domenic , Rogers-Seeley Madeline , Dean Andrew Peter
Published: September 2018

e18277

Background: Pneumocystis Jirovecii (PJP, previously Pneumocystis Carinii) infection is typically seen in those with advanced immunodeficiency such as Acquired Immunodeficiency Syndrome, haematological malignancies, sustained chemotherapy with temozolomide or patients heavily pretreated with multiple lines of chemotherapy. PJP rarely presents early in the natural history of solid tumour malignancy. We observed a cluster of cases of PJP at our institution in patients undergoing first-line chemotherapy for solid tumours. Methods: An electronic database search was conducted to identify occurrences of PJP over a 3 month period. 4 patients were identified who developed Pneumocystis Jirovecii. The patients’ records, laboratory, radiology and pathology results were examined. Results: All 4 patients identified had developed PJP during first line chemotherapy for GI malignancy. In each case, the patient presented with dyspnoea, fever and hypoxia. All were noted to be lymphopenic with lymphocyte counts of 0.2 to 0.9 x10^9/L. All were HIV negative. Chest CT revealed new bilateral ground-glass changes associated with cyst formation. All cases were found to have positive PJP PCR on testing of induced sputum. On the basis of clinical presentation, positive PCR sputum cultures and CT findings, the patients were diagnosed with PJP and treated with high-dose sulphamethoxazole and trimethoprim. 3 patients recovered and 1 died despite best ICU management. Conclusions: The relatively high number of cases of PJP early in treatment is noteworthy. It raises the question as to whether PJP is becoming more potent or that better awareness leads to earlier and more accurate diagnosis. Coincidental clustering is also a possibility. Clinicians should be aware that pneumocystis infection can occur during first-line therapy in solid tumour malignancy. It should be considered as a differential in any patient on chemotherapy (regardless of line of therapy) presenting with acute respiratory illness.
Phase IB/II study of lirilumab with azacytidine (AZA) in relapsed AML.
Authors: Daver Naval Guastad , Garcia-Manero Guillermo , Cortes Jorge E. , Basu Sreyashi , Ravandi Farhad , Kadia Tapan M. , Borthakur Gautam , Jabbour Elias , Dinardo Courtney Denton , Pemmaraju Naveen , Brandt Mark , Pierce Sherry , Hussin Nawar , Kornblau Steven Mitchell , Andreeff Michael , Konopleva Marina , Ning Jing , Allison James Patrick , Sharma Padmanee , Kantarjian Hagop M.
Published: September 2018

e18505

Background: Lack of KIR-HLA class I interactions has been associated with NK-mediated antitumor efficacy in AML patients (pts) in remission upon KIR-mismatched haploidentical stem cell transplantation (SCT) (Ruggeri L et al., Science 2002). Blockade of KIR2DL1, 2 and 3 receptors induced augmented NK-cell mediated lysis of tumor cells (Romagne F et al., Blood 2009). Hypomethylating agents possess anti-leukemia activity, increase MHC II expression, and interferon-gamma signature. Methods: Pts with AML who failed prior therapy, have adequate performance status (ECOG ≤ 2) and organ function are eligible. AZA 75mg/m2 Days 1-7 was given with lirilumab on Day 8 at the dosage of 1 and 3 mg/kg in 2 consecutive cohorts of 6 pts each. Courses were repeated every 4-5 weeks. Lirilumab 3mg/kg established as recommended phase 2-dose with AZA. 13 additional pts treated at the RP2D. Responses evaluated at the end of 3 courses. Results: To date, 25 pts (16 de novo, 9 secondary AML), median age 64 years (range, 30 – 89), 52% adverse cytogenetics, median prior therapies 3 (range, 1-8), and prior alloSCT in 6 (28%) have been enrolled. All 25 pts had baseline next generation sequencing, common mutations included ASXL1 (n = 9), TP53 (n = 7), RAS (n = 4), TET2 (n = 4), and RUNX1 (n = 3). Two (8%) achieved CR/CRi (1 CR, 1 CRi) and 3 (12%) achieved hematologic improvement for an overall response rate of 20%. The median cycles to response was 3 (range, 1-11). The 8-week mortality is 12%, respectively. The median duration of response and overall survival were 2.0 months and 4.0 months, respectively (med f/u = 5.1 months). Grade 3/4 toxicities were similar to those seen with AZA based therapies in salvage including bloodstream infections in 15 (60%), 6 pneumonia, 1 UTI, 1 skin infection, 2 abdominal pain, and 1 mucositis. Immune mediated toxicities were observed in 4 (16%) pts (1 pneumonitis Grade 3, 2 colitis Grade 3, 1 colitis Grade 2). The immune mediated toxicities responded rapidly to steroids and 3 pts could be rechallenged safely with lirilumab. Six pts were postSCT and no Grade 3/4 GVHD flares were noted. Conclusions: Full doses of AZA and lirilumab were well tolerated in heavily pretreated pts with relapsed AML. The efficacy data are still preliminary and the study is ongoing. Clinical trial information: NCT02399917.
Ten-year follow-up of pentostatin combined with cyclophosphamide, and rituximab in previously untreated indolent B-cell lymphoma.
Authors: Khashab Tamer , Niaz Muhammad Obaid , Hagemeister Fredrick B. , Romaguera Jorge Enrique , Fanale Michelle A. , Pro Barbara , McLaughlin Peter , Rodriguez Maria Alma , Neelapu Sattva Swarup , Fayad Luis , Younes Anas , Feng Lei , Berkova Zuzana , Jain Neeraj , Sehgal Lalit , Vega Francisco , Kwak Larry W. , Samaniego Felipe
Published: September 2018

e19040

Background: Frontline regimens for indolent lymphoma are effective, but patients still suffer from relapse. From 2005 to 2007 we enrolled previously untreated patients on a phase II trial to investigate response rate and efficacy of pentostatin combined with cyclophosphamide and rituximab (PCR). PCR is an effective frontline therapy in chronic lymphocytic leukemia. We report the final analysis with a median follow up of nearly ten years. Methods: Patients were treated with 6 cycles of therapy with additional 3 cycles in case of not attaining a CR/CRu. All patients received Pentostatin (4 mg/m2), Cyclophosphamide (600 mg/m2), and Rituximab (375 mg/m2) on day one and every 21 days. Results: Of the 83 patients, five were considered unevaluable for response, but are included as non-responders in our intent-to-treat analysis. Diagnoses included FL (43.4%), SLL (38.5%), and MZL (18.1%). 78.3% had Ann Arbor stage IV lymphoma and 63.9% had bone marrow (BM) involvement. For all 83 patients, the overall response was 92%, and most toxicity events were hematologic, with grade ≥3 neutropenia in 68 of 509 cycles of chemotherapy administered. Long term toxicity includes secondary malignancies in 14 patients. Two patients developed treatment related MDS/AML and both occurred after additional lines of therapy. PFS at 10 years for FL, MZL, and SLL was 71%, 67% and 15%, respectively. PFS was affected by clinicopathologic characteristics. 10-year PFS rates for those with pretreatment β2M < 2.2 and > 2.2 mg/l were 71 % and 21 % respectively. Patients without BM involvement had 10-year PFS of 72% versus 29% for those with BM involvement. The median OS has not been reached. The overall survival rate was 87% at 5 years and 64% at 10 years. The difference in OS rate was statistically significant based on histology, 94% for FL, 66% for MZL, and 39 % for SLL. Conclusions: Long term follow up confirms that PCR is an effective, robust and tolerable treatment regimen for indolent B-cell lymphomas with 34 of 36 patients with FL alive at 10 years with 27 remaining in remission. Clinical Trial Information NCT00496873 Clinical trial information: NCT00496873.
PTLD: Survival and analysis of prognostic factors in a cohort of 138 patients from a single institution.
Authors: Bishnoi Rohit , Bajwa Ravneet , Franke Aaron J , Patel Niraj , Skelton William Paul , Slayton William Birdsall , Zou Fei , Xiong Sican , Dang Nam H.
Published: September 2018

e19048

Background: The outcome and prognostic factors of post-transplant lymphoproliferative disorder (PTLD) varies in currently reported literature. We present one of the largest single institution retrospective analysis from University of Florida. Methods: Patient population was identified from EMR and charts were reviewed to collect data. Primary outcome was Overall survival (OS) and secondary outcome was identification of prognostic factors. Results: We identified 138 patients with PTLD from Sept 1994 to Feb 2016 (liver 34%, Kidney 23%, heart 21%, lungs 12%, kidney-pancreas 2% and BMT 6%). After survival analysis, 131 patients were further followed for secondary outcomes. 36% (n = 47) were less than 18 years of age, 60% (n = 83) were males. The median age of PTLD diagnosis was 44 years and the median duration from transplant to PTLD was 4.4 years. Pathology was early lesion 6% (n = 8), polymorphic 17% (n = 23), Monomorphic 71% (n = 93), Hodgkin/like 4.5% (n = 6). Extra-nodal site involvement was 61% (n = 80), most common being GI tract. Ann-Arbor stage distribution was stage I/II 50% (n = 65), stage III/IV 46% (n = 60). Initial treatment was immunosuppression (IS) reduction alone in 24% (n = 31), Rituximab (R) 24% (n = 31), chemotherapy (+/- R) 46% (n = 60). Most common chemo regimen was CHOP (+/-R) 27% (N = 36). After first line, 48% patients had complete remission (CR), 18% partial remission (PR) and 15% progressive disease (PD). Second line treatment was required in 33% (n = 44) and 10% (n = 13) patients required 3rdline treatment. Final analysis showed 61% (n = 80) achieved CR, 17% (n = 22) had PD, 56% (n = 74) patients were alive and 49% (n = 64) are alive without PTLD. Median OS was 14.99 years. Multivariate analysis identified transplant age, organ transplant recipients, PTLD diagnosis age, performance status, IPI score, graft rejection, history of malignancy and recipient EBV status as prognostic factors (p < .05). Conclusions: This study from a leading regional transplant center shows notable OS which is likely from improved immunosuppressive regimens, treatment modalities and large pediatric population. We identified various prognostic factors affecting survival and propose validation to generate prognostic score.
Conditional survival estimates for patients with plasma cell leukemia: An analysis of the SEER database.
Authors: Iyer Veena , Bagchi Arindam , Hamouda Danae , Nai Qiang , Hakim Hosam , Verghese Cherian
Published: September 2018

e19533

Background: Plasma cell leukemia (PCL) is an aggressive malignancy with poor prognosis. Retrospective studies have suggested improved outcomes with stem cell transplant and use of novel agents. Methods: We used the Surveillance, Epidemiology, and End Results database to identify 480 patients with PCL from 1973 to 2009. Kaplan Meier method was used to calculate 3-year Cancer Specific Survival (CSS) estimates, conditional on 1 to 3 years of survival (CS3). Covariates included age, sex, race and geographic location. The cohort was divided into three time frames, 1973-95, 1996-2005 and 2006-2009, to account for use of transplant from 1995 and novel agents from 2005. Results: 398 patients were selected for analysis from the initial cohort. Median age was 65. 50.75% were female and 65.8% were white. The 3-year CSS for patients with PCL was 19.6% and conditional probability of surviving additional 3 years (CS3) at 1, 2, 3 and 5 years from diagnosis was 36.9%, 51.5%, 58.5% and 71.2% respectively. CSS rates at 3 years during 1973-95, 1995-2005 and 2006-2009 were 14.7%, 12.4% and 32.9% respectively and the CS3 improved from 37.4% / 27.9% / 44.5% at 1 year to 72.7% / 46.3% / 57.5% at 3 years. 3-year CSS rates of patients aged < 50, 50-59, > 70 years was 19.9%, 19.7% and 18.7% respectively. The CS3 with each year survived increased for all age groups, with the most dramatic increase for those > 70 years (45.8% at 1 year to 80.5% at 3 years). Hispanics had the lowest 3-year CSS rate (5.5%). Improvement in CS3 from 1 to 3 years for races was as follows – Whites: 35.8% to 57.9%, Blacks: 41.9% to 50.10%, Asians: 28.6% to 67% and Hispanics: 18.7% to 33.3%. 3-year CSS rate for patients from metropolitan/non-metropolitan areas was 19.5%/18%. CS3 for metropolitan/non-metropolitan areas increased from 38.2%/27.3% at 1 year to 63%/33.3% at 3 years. Conclusions: The risk profile of patients with PCL changes as they survive past the diagnosis. Improvements in survival are more substantial in older patients and patients from metropolitan areas.
A phase 1b study of napabucasin plus weekly paclitaxel in patients with advanced thymoma and thymic carcinoma.
Authors: Hitron Matthew , Spittler Aaron John , Cote Gregory Michael , Heist Rebecca Suk , Kossler Kimiko , Li Wei , Li Youzhi , Li Chiang , Loehrer Patrick J.
Published: September 2018

e20001

Background: Napabucasin is a first-in-class cancer stemness inhibitor, identified by its ability to inhibit STAT3-driven gene transcription and spherogenesis of cancer stem cells (Li et al PNAS 112 (6):1839, 2015). Synergistic anti-tumor activity of napabucasin plus paclitaxel was observed in pre-clinical and early clinical testing. The STAT3 pathway is considered important in thymic carcinoma and thymoma, rare cancers with few treatment options. In 1st line, the objective response rate (ORR, partial response [PR] + complete response [CR] per RECIST) with carboplatin-paclitaxel was 22% in thymic carcinoma and 43% in thymoma (Gemma, 2011). A phase 1b cohort was established to evaluate safety and preliminary signs of activity of napabucasin plus paclitaxel in these patients (pts). Methods: Pts with previously-treated advanced thymoma or thymic carcinoma were enrolled with napabucasin (240 - 480 mg orally twice daily) plus paclitaxel (80 mg/m2 IV weekly for 3 of every 4 weeks). Adverse events were evaluated using CTCAE v4.03 and tumor assessments were obtained every 8 wks per RECIST 1.1. Results: A total of 9 pts (thymic carcinoma = 5, thymoma = 4) with a median 3 prior lines of systemic therapy were enrolled. In thymic carcinoma, the starting napabucasin dose was 480 mg BID (n = 2), and 240 mg BID (n = 3). Treatment was well tolerated and 1 pt required dose-reduction. There were no grade 3 AEs reported. As of data cut-off, 3 pts are off-study with progression and 2 remain on treatment. PRs were observed in 4 of 5 pts (ORR = 80%) and the median time on treatment is > 7.0 mo. In thymoma, 4 pts received napabucasin 240 mg BID. AEs included grade 3 diarrhea and dehydration in 1 pt. As of data cut-off, 1 pt was off-study with progression, 2 died (perforated bowel; autoimmune myocarditis secondary to Issac’s syndrome), and 1 pt remains on treatment. PR was observed in 1 pt (ORR 25%). Conclusions: Napabucasin plus weekly paclitaxel has demonstrated clinical safety and encouraging signs of anti-tumor activity in patients with advanced thymic carcinoma and thymoma. Further clinical evaluation of the combination regimen is warranted in this population. Clinical trial information: NCT01325441.
Cetuximab plus platinum-based chemotherapy in patients with malignant pleural mesothelioma: A single arm phase II trial.
Authors: De Paepe Annelies , Vermaelen Karim Y , Cornelissen Robin , Germonpre Paul Richard , Janssens Annelies , Lambrechts Marc , Bootsma Gerben , Van Meerbeeck Jan P. , Surmont Veerle
Published: September 2018

e20030

Background: Cetuximab is a chimeric monoclonal antibody targeting the epidermal growth factor receptor (EGFR). Previous studies suggested that cetuximab enhances chemotherapy activity in the presence of EGFR overexpression, which is present in a majority of MPM specimens. We investigated the activity and safety of the combination of platinum-based chemotherapy and cetuximab in EGFR immunohistochemical positive (IHC+) MPM patients (pts). Methods: This is an open, single arm multicenter phase II study according to a Simon 2-step design with progression-free survival (PFS) rate at 18 weeks as primary endpoint. PFS rate at 18 weeks in MPM pts with cisplatin-pemetrexed is 0.67. We hypothesized that the combination of cetuximab and chemotherapy would increase the PFS rate with 30% to 0.87 (alpha = 0.05, power 90%). 18 chemotherapy-naïve pts with epithelioid MPM and PS 0-1, EGFR IHC+ (assessed by DAKO kit with at least 1% of cells showing staining), were included in step 1 of in the study. If ≥14 were alive and free of progression at 18 weeks, sample size was to be increased to 43 pts. Treatment consisted of cisplatin (75 mg/m², day 1 of each 3-week cycle) or carboplatin AUC 5 (day 1 of each 3-week cycle) and pemetrexed (500mg/m2, day 1 of each 3-week cycle) and cetuximab (loading dose of 400 mg/m² followed by 250 mg/m² weekly) during chemotherapy until disease progression. Chemotherapy was given up to 6 cycles. Secondary end points were overall survival (OS), toxicity and response rate. Results: We enrolled 18 eligible pts between June 2010 and June 2013; 89% males, median age 68 years (range 57-80), 83% PS 1. Median number of cycles was 4 (range 2-6). Median number of weekly administrations of cetuximab was 25 (range 8-51). 13 pts were alive and without progression at 18 weeks, median PFS was 24 weeks (95% CI 18.5-29.5), median OS 49 weeks (95% CI 38.6-59.4). 44% (8/18) of patients obtained a partial response. The treatment was well tolerated; the most common adverse event was skin rash (89%), mainly grade 1-2. Conclusions: As platinum-based chemotherapy in combination with cetuximab in pts with epithelioid MPM did not reach the predefined threshold, the study was not continued. No new safety signal was observed. Clinical trial information: NCT00996567.