bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increase in time to initiating cancer therapy and association with worsened survival in curative settings: A U.S. analysis of common solid tumors.
Authors: Khorana Alok A. , Tullio Katherine , Elson Paul , Pennell Nathan A. , Kalady Matthew F. , Raymond Daniel , Klein Eric A. , Abraham Jame , Grobmyer Stephen R. , Monteleone Emily Elizabeth , Bolwell Brian James 
Published: September 2018

6557 Background: Increase in time to treatment initiation (TTI) for new cancer diagnoses causes patient distress and may adversely affect outcomes. We investigated trends in TTI for common solid tumors treated with curative intent, determinants of delayed TTI and impact on overall survival. Methods: We utilized population-based, prospective data from the National Cancer Database for newly diagnosed US patients with early-stage breast, prostate, lung, colorectal, renal and pancreas cancers from 2004-13. TTI was defined as days between diagnosis of cancer and first treatment (surgery, systemic or radiation therapy). Negative binomial regression and Cox proportional hazard models were used for analysis. Results: The study population of 3,672,561 patients included breast (N = 1,368,024), prostate (N = 944,246), colorectal (N = 662,094), non-small cell lung (NSCLC)(N = 363,863), renal(N = 262,915) and pancreas (N = 71,419) cancers. Median TTI increased from 21 days in 2004 to 29 days in 2013 (P < 0.0001). Aside from year, determinants of delays included care at academic centers and change in treating facility. Increased TTI was associated with worsened overall survival (OS) for stages I and II breast, lung, renal, and pancreas cancers, and stage II colorectal cancers, with hazard ratios per week of delay ranging from1.005 (1.002-1.008) to 1.030 (1.025-1.035), adjusting for comorbidities and other variables. Prolonged TTI ( > 6 wks) was associated with substantially worsened OS e.g., 5-yr OS for stage I NSCLC was 56% (±0.2) for TTI ≤ 6wks v 43% (±0.2) for TTI > 6 wks and for stage I pancreas was 38% (±0.6) v 29% (±1) respectively (P < 0.0001 for both). Conclusions: TTI has lengthened significantly over recent years, associated with multiple factors. Increase in TTI is associated with substantial increase in mortality ranging from 0.5-3.2% per week of delay in curative settings such as early-stage breast, lung and pancreas cancers. Simplifying access and navigation of complex health systems is essential to diminish this apparently iatrogenic impact on outcomes.
PROMs and PREMs in Dutch integrated head and neck cancer care.
Authors: Hermens Rosella , van Overveld Lydia Francisca Jacoba , Takes Robert P. , Braspenning Jozé C.C. , Smeele Ludi E , Merkx Matthias A.W. 
Published: September 2018

6570 Background: Providing patient-centred care is an essential component of high quality integrated care. A method to get insight in patients perspectives about the quality of health care they received, is measuring Patient Reported Outcome Measures (PROMs) and Patient Reported Experience Measures (PREMs). We aimed to determine the outcomes of, and differences between PROs and PREs over time and between treatment groups for patients with head and neck cancer (HNC). Methods: Patientswere recruited from nine hospitals participating in the DHNA. Validated questionnaires were distributed at baseline, 3, 6 and 12 months follow-up. Included PROMs were EuroQol 5 Dimension 3 Level (EQ-5D-3L), EORTC QLQ-C30 and -H&N35. Included PREMs, Consumer Quality index for Oncologic care (CQO) and Radiotherapeutic care (CQR), have similar domains with different questions. With descriptive analysis, ANOVA and mixed model analysis, differences over time and between treatment groups were analyzed. Results: Questionnaires were filled in by 426 patients. Pain decreased significantly at 6 and 12 months follow-up (14 and 21 points on a scale of 0-100) and dry mouth increased significantly at 3, 6 and 12 months follow-up compared to baseline (35, 27 and 20 points). Sticky Salvia, problems with social eating and sense problems increased at 3 and 6 months follow-up, but were similar to the baseline score at 12 months follow-up. Pain and sticky saliva differed between radiotherapy and chemoradiotherapy or surgery and radiotherapy respectively (p≤0.05). Regarding the CQO domain scores, all treatment groups differed significantly from each other (p≤0.05), especially for the domain Personal input. There was no difference regarding the CQR domain scores. Recognizing the emotional side of HNC and guidance after the treatment scored low in patients. Conclusions: This study gives clues to improve healthcare according the experiences of the patient and we can predict more carefully the outcomes of the patients with different treatment types. PROMs according to the ICHOM criteria and PREMs are promising for measuring and improving quality and personalization of HNC care. However, recognizing the emotional side of HNC and intensifying guidance after the treatment period needs improvement.
CEASE: A novel patient directed electronic smoking cessation platform for cancer patients.
Authors: Jones Jennifer M. , Liu Geoffrey , Selby Peter , Eng Lawson , Goldstein David Paul , Giuliani Meredith Elana 
Published: September 2018

6584 Background: Continued smoking in cancer patients receiving treatment results in decreased efficacy, reduced survival, amd increased risk of recurrence. Despite ASCO and AACR policy statements, routine tobacco use screening and provision of smoking cessation treatment has not been widely implemented in the cancer setting. A paper-based tobacco use screening and clinician-dependent referral program for new ambulatory cancer patients was initiated at Princess Margaret Cancer Centre in 2013 resulting in moderate screen rates but low referral rates. In response, we developed and implemented a tailored patient directed electronic smoking cessation platform (CEASE) which included three elements:1) tobacco use assessment tool; 2) patient education on benefits of cessation; 3) a patient directed automatic referral system to smoking cessation programs. Methods: Interrupted time series design to examine the impact of CEASE on process of care (screening rates, referrals offered and accepted) and patient reported (quit attempts, smoking status, uptake of cessation programs) outcomes. Included 20 monthly intervals: 6 pre implementation (Apr-Sept 2015) (PRE), 8 gradual implementation across all tumour sites (Oct 2015-May 2016), and 6 postb implementation (Jun 2016-Nov 2016) (POST). A time series segmented linear regression was conducted to evaluate changes in process of care outcomes (excluding the implementation period). Pre-post self-report patient outcome data was also compared. Results: We assessed data from n = 3785 (PRE) and n = 4726 (POST) new patients. Screening rates increased from 44% using the paper-based approach to 65% with CEASE (p = 0.0019). Referrals offered to smokers who were willing to quit increased from 24% to 100% (p < 0.0001). Accepted referrals decreased from 45% to 26%; though the overall referral rate increased from 11% to 26% (p = 0.0001). The proportion of those using tobacco or attempting to quit did not differ at 3-months. However, engagement with the referral source increased from 4% to 62.5% (p < 0.001). Conclusions: CEASE was successfully implemented across all clinics and resulted in improvements in overall screening and referral rates and engagement with referral services.
Validity and reliability of four value frameworks for cancer drugs.
Authors: Bentley Tanya GK , Cohen Joshua T. , Elkin Elena B. , Huynh Julie , Mukherjea Arnab , Neville Thanh H. , Mei Matthew Genyeh , Copher Ronda , Knoth Russell L. , Popescu Ioana , Lee Jackie , Zambrano Jenelle , Broder Michael 
Published: September 2018

6603 Background: Little is known about the validity and reliability of value assessment frameworks. Methods: Eight panelists used the ASCO, ESMO, ICER, and NCCN frameworks to conduct value assessments of 15 drugs for advanced lung and breast cancers and castration refractory prostate cancer. Panelists received instructions and published clinical data to complete the assessments, assigning each drug a numeric or letter score. We used Kendall’s W coefficient to measure convergent validity by cancer type among frameworks and intraclass correlation coefficients (ICC) to measure framework inter-rater reliability across cancers. Panelists were surveyed on their experiences. Results: Kendall’s W for breast, lung, and prostate cancer drugs were 0.560 ( p= 0.010), 0.562 ( p= 0.010), and 0.920 ( p< 0.001), respectively. Pairwise and subdomain W are shown in the table. ICC (95% CI) for ASCO, ESMO, ICER, and NCCN were 0.800 (0.660-0.913), 0.818 (0.686-0.921), 0.652 (0.466-0.834), and 0.153 (0.045-0.371), respectively. Panelists generally agreed the frameworks were logically organized and easy to use. Conclusions: Convergent validity among the frameworks was fair to excellent, increasing with clinical benefit subdomain concordance and simplicity of drug trial data. Inter-rater reliability, highest for ASCO and ESMO, improved with clarity of instructions and specificity of score definitions. Continued use, analyses, and refinements of the frameworks will bring us closer to using value-based treatment decisions to improve patient care and outcomes. [Table: see text]
Impact of intravenous cancer drug wastage on economic evaluations.
Authors: Truong Judy , Cheung Matthew C. , Mai Helen , Letargo Jessa , Chambers Alexandra , Sabharwal Mona , Trudeau Maureen E. , Chan Kelvin K. 
Published: September 2018

6607 Background: Intravenous drugs administered through body-surface area (BSA) or weight-based dosing may cause wastage due to large and/or limited fixed vial sizes, and vial sharing restrictions. Drug wastage leads to incremental costs without incremental value to patients. Bach et al. (2016) estimated 10% of revenue ($1.8 billion) from cancer drugs would result from wastage in 2016. The pan-Canadian Oncology Drug Review (pCODR) committee provides recommendations on which drugs to publicly reimburse by reviewing clinical and economic evidence. There is considerable potential that drug wastage could impact the economic evaluations. We sought to determine the impact of modeling cancer drug wastage on the results of economic evaluations. Methods: Economic evaluations submitted by drug manufacturers and reviewed by the pCODR Economic Guidance Panel (EGP) were assessed for frequency of wastage reporting and modeling. Cost-effectiveness analyses and budget impact analyses were conducted for scenarios in which “no wastage” and “wastage” of drugs occurred. Sensitivity analyses were performed to determine the effects of BSA and weight variation. Results: 12 drugs for use in 17 indications were analyzed. Wastage was reported in 71% and incorporated in 53% of manufacturer’s models, resulting in a mean incremental cost-effectiveness ratio (ICER) increase of 6.1% (range: 1.3% to 14.6%). EGP reported and incorporated wastage for 59% of models, resulting in a mean ICER increase of 15.0% (2.6% to 48.2%). When maximum wastage (i.e. the entire unused portion of each vial is discarded) was incorporated in our independent analysis, the mean ICER increased by 24.0% (0.0% to 97.2%) and the mean 3-year total incremental costs increased by 26.0% (0.0% to 83.1%). Over a 3-year period, wastage can increase the total incremental drug budget cost by CAD $102 million nationally. Changing the mean BSA or body weight caused 45% of the drugs to use a different vial size (if available) and/or quantity, resulting in further increased drug costs. Conclusions: Wastage can have an under-recognized and significant impact on economic evaluations of intravenous chemotherapy drugs. Guidelines are needed to promote uniform and optimal modeling of drug wastage in economic evaluations.
Cost-effectiveness of ovarian cancer screening: An analysis of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) from a U.S. health system perspective.
Authors: Moss Haley , Myers Evan , Berchuck Andrew , Havrilesky Laura Jean 
Published: September 2018

6608 Background: UKCTOCS is the largest randomized controlled trial to evaluate screening’s impact on ovarian cancer mortality, assigning women to multimodal screening (MMS) with serum CA125 interpreted with a risk algorithm; annual transvaginal ultrasound; or no screening (NS). There was a non-statistically significant 15% reduction in mortality over 11 years in MMS group. As most of the potential benefit of screening was seen after 7 years, follow-up is ongoing to determine if an observed stage shift translates into significant mortality reduction. The current study estimates the cost-effectiveness of an MMS screening program in the US. Methods: A modified Markov model was constructed using data from UKCTOCS to compare MMS to NS. Published estimates of the long term effect of MMS screening on ovarian cancer mortality were used to simulate mortality over 40 years from the start of screening. Base case costs included CA125, ultrasounds, clinical evaluations and false-positive surgeries, with an annual weighted cost of $35 in addition to an estimated risk algorithm cost of $100. The utility and costs of ovarian cancer treatment were incorporated into the model. Incremental cost-effectiveness ratios (ICERs) were calculated in 2016 U.S. dollars per quality-adjusted year of life saved (QALY). Additional sensitivity analyses were performed. Results: MMS is both more expensive and more effective in reducing ovarian cancer mortality over a lifetime than NS. Screening women from age 50 to 75 with MMS reduced mortality by 24% with an ICER of $98,062/QALY. If screening begins at age 60, MMS reduces mortality by 12%, with ICER below the willingness to pay threshold of $100,000/QALY only if the algorithm costs < $50. In probabilistic sensitivity analyses, the probability that screening from age 50-75 at an algorithm cost of $100 was less than $100,000/QALY was 41%. Conclusions: Ovarian cancer screening is potentially cost-effective in the US depending on final significance of mortality reduction and cost of the CA-125 risk algorithm. These results are limited by uncertainty around the effect of screening on ovarian cancer mortality beyond the 11 years of UKCTOCS.
Cost-effectiveness analysis of first-line treatments for early-stage, low-grade follicular lymphoma.
Authors: Yang Joanna C. , Elkin Elena B. , Parikh Rahul , Yahalom Joachim 
Published: September 2018

6619 Background: Low-grade follicular lymphoma (FL) can present as localized stage I to II disease in up to one-third of patients. Upfront involved-site radiation therapy (RT) to 24-30Gy is the preferred first-line management strategy for these patients. However, the National LymphoCare Study found that less than one quarter of patients with early-stage, low-grade FL received upfront RT, while more than half received either chemoimmunotherapy or observation. Methods: We performed a cost-effectiveness analysis using a Markov state-transition model to simulate the progression of early-stage, low-grade FL in a cohort of 60-year-old men. The following first-line treatments were compared: RT, observation, rituximab induction (RI), rituximab and bendamustine (BR), and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (RCHOP). Patients who relapsed received second-line therapies that were dependent on their first-line treatment: RT for RI and observation, RCHOP for RT and BR, and BR for RCHOP. Disease-progression probabilities and other model inputs were from published trials. Results: First-line RT followed by RCHOP for relapses had a quality-adjusted life expectancy (QALE) of 11.4 years, superior to first-line observation, RI, BR, and RCHOP strategies. First-line RT strongly dominated observation, BR, and RCHOP. Compared with RI, first-line RT resulted in an incremental cost-effectiveness ratio of $2,740 per quality-adjusted life year. The probability of dying from other causes, the probability of a complete response to RT, and the probability of relapse had the greatest impact on both cost and effectiveness expected values. Conclusions: In contrast to current practice patterns, first-line RT is the most effective upfront treatment for patients with early-stage, low-grade FL. Further, first-line RT paired with RCHOP for relapses is a cost-effective treatment paradigm, relative to other strategies. [Table: see text]
Algorithmic matching of genomic profiles to precision cancer medicine clinical trials at DFCI.
Authors: Lindsay James , Del Vecchio Fitz Catherine , Zwiesler Zachary , Kumari Priti , Do Khanh Tu , Shapiro Geoffrey , Cerami Ethan 
Published: September 2018

6620 Background: Genomic profiling and access to precision medicine clinical trials are now standard at leading cancer institutes and many community practices. Interpreting patient-specific genomic information and tracking the complex criteria for precision medicine trials requires specialized computational tools, especially for multi-institutional basket studies such as NCI-MATCH and TAPUR. Methods: To address this challenge we have developed an open source computational platform for patient-specific clinical trial matching at Dana-Farber Cancer Institute (DFCI) called MatchMiner, which aides in both patient recruitment to precision medicine trials, as well as decision support for oncologists. Trial matches are computed based on genomic criteria, including mutations, CNAs, and SVs, as well as clinical and demographic information, including cancer type, age, and gender. A formal standard called clinical trial markup language (CTML) to encode complex clinical trial eligibility criteria has also been created. Results: MatchMiner is now available at DFCI. Currently 123 precision medicine clinical trials have been transformed into CTML and 13,000 patient records are available, with over 88% of current patients having at least 1 match (average 2.6). A total of 103 genes are specified as criteria for at least 1 trial. KRAS, TP53, PTEN, PIK3CA and BRAF are the genes driving the most number of matches. General usage statistics and trial enrollment rates are currently being monitored to determine the system effectiveness. As this is an open source initiative, the software is also now publically available at https://github.com/dfci/matchminer. Conclusions: We have developed an open source computational platform that enables patient-specific matching and recruitment to precision medicine clinical trials at DFCI. We are actively seeking collaborators and plan to make CTML a multi-institution standard for encoding complex clinical trial eligibility in a computable form.
Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia (R/R AML): Results of a phase I dose-escalation and expansion study.
Authors: Stein Eytan M. , Dinardo Courtney Denton , Pollyea Daniel Aaron , Fathi Amir Tahmasb , Roboz Gail J. , Altman Jessica K. , Stone Richard M. , Flinn Ian , Kantarjian Hagop M. , Collins Robert , Patel Manish R. , Stein Anthony Selwyn , Sekeres Mikkael A. , Swords Ronan T. , Medeiros Bruno C. , Knight Robert D. , Agresta Samuel V. , de Botton Stéphane , Tallman Martin S. 
Published: September 2018

7004 Background: Recurrent mutations in isocitrate dehydrogenase 2 (m IDH2) occur in 8-15% of AML pts. mIDH2 proteins synthesize an oncometabolite, 2-hydroxyglutarate (2HG), causing DNA and histone hypermethylation and blocked myeloid differentiation. Enasidenib (AG-221) is an oral, selective, small-molecule inhibitor of mIDH2 protein. Methods: This phase 1/2 study assessed the maximum tolerated dose (MTD), pharmacokinetic and pharmacodynamic profiles, safety, and clinical activity of enasidenib in pts with m IDH2 myeloid malignancies. Safety for all pts and efficacy outcomes for R/R AML pts from the phase 1 dose-escalation and expansion phases are reported. Results: In all, 239 pts received enasidenib. In the dose-escalation (n=113), the MTD was not reached at doses up to 650 mg daily. Median 2HG reductions from baseline were 92%, 90%, and 93% for pts receiving <100 mg, 100 mg, and >100 mg daily, respectively. Enasidenib 100 mg QD was chosen for the expansion phase (n=126) based on PK/PD profiles and demonstrated efficacy. Median number of enasidenib cycles was 5 (range 1–25). Grade 3-4 drug-related investigator reported AEs included indirect hyperbilirubinemia (12%) and IDH-inhibitor-associated differentiation syndrome (ie, retinoic acid syndrome; 7%). For R/R AML pts, overall response rate (ORR) was 40.3%, including 34 (19.3%) complete remissions (CR; Table). Response was associated with cellular differentiation, typically with no evidence of aplasia. Median overall survival (OS) for R/R AML pts was 9.3 months (mos). For pts who attained CR, OS was 19.7 mos. Pts who had received ≥2 prior AML regimens (n=94; 53%) had median OS of 8.0 mos. Conclusions: Enasidenib was well tolerated, induced CRs, and was associated with OS of >9 mos in pts who had failed prior AML therapies. Differentiation of myeloblasts, not cytotoxicity, appears to drive the clinical efficacy of enasidenib. Clinical trial information: NCT01915498. [Table: see text]
Updated results of a phase I/II study of inotuzumab ozogamicin in combination with low-intensity chemotherapy (mini-hyper-CVD) as frontline therapy for older patients with acute lymphoblastic leukemia.
Authors: Short Nicholas James , Kantarjian Hagop M. , O'Brien Susan Mary , Ravandi Farhad , Thomas Deborah A. , Garcia-Manero Guillermo , Daver Naval Guastad , Borthakur Gautam , Jain Nitin , Konopleva Marina , Sasaki Koji , Pemmaraju Naveen , Alvarado Yesid , Jacob Jovitta , Garris Rebecca , Thompson Philip A. , Cortes Jorge E. , Jabbour Elias 
Published: September 2018

7014 Background: Inotuzumab ozogamicin (InO) is an anti-CD22 antibody-toxin conjugate that is effective in patients (pts) with relapsed/refractory ALL. Given the poor tolerance of elderly pts to intensive chemotherapy, we evaluated the safety and efficacy of low-intensity chemotherapy (mini-hyper-CVD) plus InO as frontline treatment for older pts with newly diagnosed ALL. Methods: Pts ≥60 years of age with newly diagnosed Ph-negative pre-B ALL received mini-hyper-CVD (no anthracycline, dose reductions of cyclophosphamide, dexamethasone, MTX and Ara-C). Pts received InO 1.3-1.8 mg/m2 on day 3 of cycle 1 and 0.8-1.3 mg/m2 on day 3 of cycles 2-4. Rituximab (if CD20+) and prophylactic IT chemotherapy were given for the first 4 cycles. Responding pts received POMP maintenance for up to 3 years. Results: 47 pts have been treated, 4 of whom were in CR at enrollment. Median age was 68 years (range, 60-81) and median CD22 expression was 97% (range, 72-100%). Among 43 pts evaluable for response, 41 (95%) achieved CR or CRp (CR, n = 36, CRp, n = 5). 1 pt achieved CRi and 1 did not respond. MRD negativity by 6-color flow cytometry was achieved in 31/41 pts (76%) after 1 cycle and in 44/46 pts (96%) overall. Median times to platelet and ANC recovery in cycle 1 were 23 and 16 days, respectively, and for subsequent cycles were 22 and 17 days, respectively. Prolonged thrombocytopenia ( > 6 weeks) occurred in 37 pts (79%). 4 pts (9%) developed VOD, 1 after allogeneic stem cell transplant (ASCT) and 3 unrelated to ASCT. Only 1 pt developed severe VOD. Among 46 responders, 6 (13%) relapsed, 3 (7%) underwent ASCT in CR1, 27 (59%) remain on treatment or have completed maintenance, and 10 (22%) died in CR/CRp. With a median follow-up of 24 months, the 3-year continued remission and OS rates were 72% and 54%, respectively. Compared to a historical cohort of older pts treated with hyper-CVAD ± rituximab (n = 79), mini-hyper-CVD + InO resulted in significantly higher 3-year OS (54% vs 31%; P = 0.007). Conclusions: Mini-hyper-CVD plus InO is safe and effective in elderly pts with newly diagnosed ALL and appears to improve outcomes compared to hyper-CVAD in this population. Clinical trial information: NCT01371630.