bluuebunny/crossref_metadata_2025 huggingface dataset:
Progression-free survival (PFS) as surrogate endpoint for overall survival (OS) in clinical trials of HER2-targeted agents in HER2-positive metastatic breast cancer (MBC): An individual patient data (IPD) analysis.
Authors: Michiels Stefan , Pugliano Lina , Grun Delphine , Barinoff Jana , Cameron David A. , Cobleigh Melody A. , Di Leo Angelo , Johnston Stephen R. D. , Gasparini Giampietro , Kaufman Bella , Marty Michel E. , Nekljudova Valentina , Paluch-Shimon Shani , Penault-Llorca Frederique , Slamon Dennis J. , Vogel Charles L. , Von Minckwitz Gunter , Buyse Marc E. , Piccart-Gebhart Martine J.
Published: March 2020

610

Background: The gold standard endpoint in randomized clinical trials (RCTs) in MBC is OS, which has the disadvantage of requiring extended follow-up and being confounded by subsequent anti-cancer therapies. Although therapeutics have been approved based on PFS, its use as a primary endpoint is controversial. This study, the first IPD meta-analysis of targeted agents in MBC, aimed to collect data from RCTs of HER2-targeted agents in HER2+ MBC, assessing to what extent PFS correlates with, and may be used as, a surrogate for OS. Methods: A search was conducted in April 2011. Eligible RCTs accrued HER2+ MBC patients (pts) in 1992-2008. Collaboration was obtained from industrial partners (Roche, GSK) for industry-led studies. Investigator-assessed PFS was defined as the time from randomization to clinical or radiological progression, or death. A correlation approach was used: at the individual level, to estimate the association between PFS and OS using a bivariate survival model and at the trial level, to estimate the association between treatment effects on PFS and OS. Squared correlation values close to 1.0 would indicate strong surrogacy. Results: The search strategy resulted in 2137 eligible pts in 13 RCTs testing trastuzumab or lapatinib. We collected IPD data from 1963 pts in 9 RCTs. One phase II RCT did not have sufficient follow-up data so that 1839 pts in 8 RCTs were retained (5 evaluating trastuzumab, 3 lapatinib); 6 out of 8 RCTs were first-line. At the individual level, the Spearman rank correlation using Hougaard copula was equal to r=0.66 (95% CI 0.65 to 0.66) corresponding to an r2 of 0.42. At the trial level, the squared correlation between treatment effects on PFS and OS was provided by R2=0.33 (95% CI -0.22 to 0.86) using Hougaard copula and R2=0.53 (95% CI 0.22 to 0.83) using log hazard ratios from Cox models. Conclusions: In RCTs of HER2-targeted agents in HER2+ MBC, PFS is moderately correlated with OS and treatment effects on PFS are modestly correlated with treatment effects on OS, similarly to first-line chemotherapy in MBC (Burzykowski et al JCO 2008). PFS does not completely substitute for OS.
Adverse prognostic impact of intratumor heterogeneous HER2 gene amplification in patients with breast cancer.
Authors: Criscitiello Carmen , Viale Giuseppe , Disalvatore Davide , Bagnardi Vincenzo , Fumagalli Luca , Gelao Lucia , Locatelli Marzia Adelia , Rotmensz Nicole , Goldhirsch Aron , Curigliano Giuseppe
Published: March 2020

617

Background: There is increasing recognition of the existence of intratumoral heterogeneity of the human epidermal growth factor receptor (HER2), which affects interpretation of HER2 positivity in clinical practice and may have implications for patient prognosis and treatment. Only patients (pts) with HER2 positivity - defined as 3+ by IHC or FISH amplified defined as a HER2 gene to chromosome 17 (HER2/CEP17) ratio ≥ 2.0 - are eligible to receive trastuzumab treatment. Limited information is available on the prognosis of pts with HER2 2+ or FISH test with a HER2/CEP17 ratio < 2.0. Methods: We retrospectively analyzed data from 455 consecutive early BC pts with HER 2+ and HER2/CEP17 ratio < 2.0 who underwent surgery after 2007. The association between HER2/CEP17 ratio and other known prognostic factors was evaluated with multivariable linear regression models. The role of HER2/CEP17 ratio on recurrence free survival was assessed with multivariable Cox regression models. Results: Fifty-one percent of the evaluated pts were node negative, 51% were postmenopausal, 93% had ER positive BC and 85% had Ki-67 ≥14%. The mean HER2/CEP17 ratio was 1.27 (SD=0.3). A significant positive relationship between HER2/CEP17 ratio and Ki-67 was observed (p<0.01). During a median follow-up time of 2.7 years, 40 recurrences were observed (15 locoregional events and 25 distant metastases). Overall, the association between HER2/CEP17 and the risk of recurrence was not significant. From subgroup analysis, a significant interaction between HER2/CEP17 ratio and nodal involvement emerged (p=0.02). Among pts with node-negative disease, pts with HER2/CEP17 ratio ≥1.27 were at higher risk of recurrence with respect to pts with HER2/CEP17 ratio < 1.27 (adjusted HR 4.0, 95% CI 1.01-15.9). Conclusions: Among pts with BC and HER2 intratumoral heterogeneity, HER2/CEP17 ratio ≥1.27 could have a strong prognostic role in node negative HER2 2+ BC, thus suggesting potential future therapeutic approaches in this setting of pts.
When less is better: Safety and efficacy of combination of trastuzumab and continuous low oral dose chemotherapy (HEX) as first-line therapy for HER2-positive advanced breast cancer (ABC)—First early results from a phase II trial on behalf of Gruppo Oncologico Italia Meridionale (GOIM).
Authors: Orlando Laura , Giotta Francesco , Cinefra Margherita , Rizzi Daniele , Pisconti Salvatore , Del Prete Salvatore , Ciccarese Mariangela , Rinaldi Antonio , Schiavone Paola , Quaranta Annamaria , Fedele Palma , Nacci Angelo , Calvani Nicola , Lorusso Vito , Colucci Giuseppe , Cinieri Saverio ,   Gruppo Oncologico Italia Meridionale (GOIM)
Published: March 2020

618

Background: Clinical activity of the combination of chemotherapy plus trastuzumab in HER2+ ABC has been well documented. We report the first results in terms of activity and safety of the combination of trastuzumab plus metronomic capecitabine and cyclophosphamide as first line therapy in HER-2 positive ABC. Methods: Patients (pts) at first relapse or with synchronous metastasis, were treated with trastuzumab (4 mg/kg, loading dose 6 mg/kg) plus oral capecitabine (1500mg/daily) and cyclophosphamide (50 mg/daily). Primary end-point was overall response rate (ORR), secondary end-points time to progression (TTP), clinical benefit rate (CBR; PR+ CR + prolonged SD for ≥ 24 weeks) and tolerability. The optimal two-stage design was applied. Results: A total of 31 pts with measurable ABC, tumors scored as +3 positive for HER-2 or FISH +, no pretreated with chemotherapy or trastuzumab for advanced disease have been enrolled, 28 actually valuable for response and toxicity. Median age was 59 years (range 42-87), visceral metastases were present in most patients (61%). Median number of cycles was 12 (range 1-37+). The ORR was 61 % (95% CI, 41-78%), with 1 CR (3.6 %) and 16 PR (57.1%). 9 patients had prolonged SD (32%). The CBR was 82.1% (95% CI , 63%-94%). Five progressions were observed (18%). Median TTP was 7 months (range 2- 19 + months). Ten pts received more than 20 courses. Worst toxicities were grade 2 hand-foot syndrome in 4 pts, grade 2 anemia in 4 pts, grade 2 nausea in 2 pts and diarrhea grade 3 in 1 pt. Cardiac toxicity grade 2 in 1 pts. Alopecia was not reported. Conclusions: Combination of trastuzumab and low dose metronomic oral chemotherapy in HER-2 + breast cancer has shown clinical activity. The tolerability was excellent and allowed the prolonged delivery of the combination. Thus, the patients accrual is ongoing to the pre-set target of 66 patients. Clinical trial information: 2009-017083-16.
Elevated pretreatment serum biomarkers and correlation with progression-free (PFS) and overall survival (OS) in first-line trastuzumab-treated metastatic breast cancer.
Authors: Ali Suhail M. , Leitzel Kim , Anyanwu Uchechi , Hou Hui Ying , Evans Matthew Stephen , Shrivastava Vikas , Köstler Wolfgang , Fuchs Eva-Maria , Esteva Francisco J. , Carney Walter P. , Lipton Allan
Published: March 2020

622

Background: Approximately one-half of HER2-positive breast cancer patients will respond tofirst-line trastuzumab-containing therapy. However, in those patients with an initial trastuzumab response, most will progress within a year with acquired resistance. Since trastuzumab treatment is also now used in the HER2-positive adjuvant breast cancer setting, trastuzumab resistance will continue to be a recurring clinical problem, and better predictive and prognostic biomarkers are urgently needed. Methods: Seven serum biomarkers (carbonic anhydrase 9 (CA9), endoglin, HER2, IGF-1R, tissue inhibitor of metalloproteinase-1 (TIMP-1), urokinase-type plasminogen activator (uPA), and VEGF-A (isoform 165) were measured using ELISA assays in 81 metastatic breast cancer patients before starting first-line trastuzumab-containing therapy. The endoglin and IGF-IR ELISAs were from R&D Systems; others were from WILEX/Oncogene Science, Cambridge, MA. PFS and OS were analyzed using the Kaplan-Meier method and Cox modeling with continuous pretreatment serum biomarker variables. Results: For univariate PFS analysis, higher pretreatment serum biomarkers (except IGF-1R and VEGF-A) predicted reduced PFS (p<0.05) to first-line trastuzumab-containing therapy. In multivariate PFS analysis, only serum CA9 (p= 0.038) remained a significant independent covariate. In univariate OS analysis, higher pretreatment serum biomarkers (except IGF-1R and VEGF-A) were prognostic for reduced OS (p<0.05). In multivariate analysis for OS, TIMP-1 (p=0.001) and CA9 (p=0.04) remained significant independent prognostic factors, as well as line of chemotherapy (3 vs. 2 or 1 line)(p=0.005), and hormone receptor status (ER and/or PR positive vs. negative)(p=0.013). Conclusions: Higher pretreatment serum CA9 (a marker of hypoxia) predicted reduced PFS, and higher serum CA9 and TIMP-1 predicted reduced OS in metastatic breast cancer patients treated with first-line trastuzumab-containing therapy. These serum biomarkers deserve further study in larger trials of HER2-targeted breast cancer treatment. Supported by a grant from Komen for the Cure.
Estimated life years saved with trastuzumab in first-line HER2+ metastatic breast cancer from 1999 to 2013.
Authors: Danese Mark , Lalla Deepa , Brammer Melissa , Santos Eduardo , Lee Abraham , Masaquel Anthony
Published: March 2020

625

Background: Trastuzumab was approved in the United States (US) in September 1998 for the treatment of HER2+ metastatic breast cancer (MBC). This model estimates the total number of life years saved (LYS) in US women treated with trastuzumab over a 15-year period (1999-2013). Methods: Using US population estimates and cancer registry-based incidence data, we estimated the number of women with recurrent stage I-III or de novo stage IV HER2+ MBC by year, age, hormone receptor, and nodal status. Trastuzumab utilization was based on published studies of HER2 testing rates, true positive rates in the community, and treatment initiation rates. Survival was estimated by extrapolating survival data pooled across 5 trials and 2 observational studies separately for women treated with trastuzumab and with chemotherapy alone. Few studies reported survival in women with HER2+ MBC without trastuzumab (N=3). Sensitivity analyses were conducted by estimating overall survival from the initial phase 3 trial (67% of placebo patients crossed over to trastuzumab after progression; HR=0.80), and assuming a higher risk reduction to account for crossover effects in clinical trials (HR=0.60). Results: In the base case, approximately 83,462 women with HER2+ MBC were estimated to receive 1st line trastuzumab over a 15-year period. The pooled median overall survival across studies without and with trastuzumab was 21.2 and 35.5 months, respectively. Patients were projected to live a total of 216,290 life years if trastuzumab had not been available and if they received chemotherapy only. These same patients were estimated to live a total of 294,877 life years with first-line trastuzumab, for an incremental benefit of 78,587 LYS. In sensitivity analysis, total LYS ranged from 48,334-96,360. Conclusions: Real-world evidence supports a median overall survival of approximately 36 months in women with HER2+ MBC receiving 1st line trastuzumab. Using a population-based, conservative model, we found that trastuzumab use has resulted in > 75,000 life years over 15 years in women with HER2+ MBC. Future research is warranted to examine the characteristics, experiences, and outcomes among women living longer with HER2+ MBC.
What are NCI-designated cancer centers using for breast cancer HER2 testing?
Authors: Siziopikou Kalliopi P. , Weldon Christine B. , Trosman Julia R. , Gradishar William John , Schink Julian C.
Published: March 2020

626

Background: After 15 years of HER2 testing in breast cancer, various testing methods are used in practice. Studies comparing methods are published but no consensus exists on which method is best. Our study provides a benchmark on the use of breast HER2 testing methods in leading U.S. cancer centers. Methods: We conducted an IRB-approved web survey of 58 NCI cancer centers (pathologists and oncologists) providing adult breast cancer care. The survey included 14 questions on breast HER2 testing methods, and reflex and retest practices. We analyzed results using simple frequencies and Fisher's exact test. Results: We achieved a response rate of 98% (57/58 sites). In this cohort, 42% (24/57) of sites conduct HER2 testing for breast cancer using an IHC method with reflex to FISH. Of these, all sites reflex IHC 2+ results and 54% (13/24) automatically reflex IHC results beyond 2+ (see table, results are not mutually exclusive). Concurrent primary FISH and IHC testing is conducted at 32% (18/57) of sites; FISH only testing at 18% (10/57); concurrent primary SISH and IHC testing at 5% (3/57); concurrent primary CISH and IHC testing at 2% (1/57), and CISH only testing at 2% (1/57) of sites. The choice of testing protocol had no correlation with the size of institution, metro vs rural location, NCCN membership, or whether the site acts as a reference lab. However, sites where oncologists always or often request a specific test method were more likely (75%, 21/28) to use FISH as a primary method vs as a reflex method (38%, 9/24), p=.0108. Repeat HER2 testing on surgical tumor samples, after the core biopsy, was reported by 47% of sites (27/57); retesting of relapsed patients by 63% (36/57); and retesting for progressive metastatic disease by 56% (32/57). Conclusions: For HER2 breast biomarker testing, concurrent FISH and IHC testing and expanded reflex testing, beyond IHC 2+ results, have become a common practice at the NCI designated cancer centers. [Table: see text]
Double-blind, randomized, parallel group, phase III study to demonstrate equivalent efficacy and comparable safety of CT-P6 and trastuzumab, both in combination with paclitaxel, in patients with metastatic breast cancer (MBC) as first-line treatment.
Authors: Im Young-Hyuck , Odarchenko Petro , Grecea Daniela , Komov Dmitry , Anatoliy Chernobay Valentynovych , Gupta Sudeep , Shparyk Yaroslav V. , Caguioa Priscilla B. , Makhson Anatoly , Krasnozhon Dmitriy , Li Rubi Khaw , Noryk Dzmitry , Vinnyk Yurii Oleksiiovych , Nemsadze Gia , Kim Ho Ung , Lee Sang-Joon
Published: March 2020

629

Background: CT-P6(C) is an anti-HER2 MoAb, a biosimilar to trastuzumab (T). This trial is a global phase III study to compare C with T, both in combination with paclitaxel (P) as first-line treatment in women with HER2+ MBC. Methods: 475 patients with centrally confirmed HER2+ MBC were randomized to receive either C+P (n=244) or T+P (n=231). Patients had to have a baseline LVEF ≥50% and no history of serious cardiac disease. Study medication was as follows: C or T 8 mg/kg i.v. (day 1), followed by 3-weekly C or T 6 mg/kg. P (175 mg/m23-weekly) was co-administered. The primary endpoint was overall response rate (ORR) as determined by independent review. Pooled analysis with data from phase I/IIb (NCT01084863) and III studies (NCT01084876) was predefined and endorsed by the EMA. Patient safety was monitored throughout the study by an independent data monitoring committee. Treatment was continued until disease progression, death or patient’s withdrawal. Results: In the pooled ITT population, ORR was 57% for C+P and 62% for T+P (difference: 5%; 95% CI: -0.14, 0.04) during the first 8 cycles of treatment. The limits of the 95% CIs for the difference in the proportions of responders were contained within the pre-defined range [-0.15, 0.15] required for equivalence. Median time to progression and median time to response were 11.07 vs. 12.52 months (P =0.10), and 1.38 vs. 1.38 months (P =0.37) for C+P and T+P, respectively. Frequency of treatment-related AEs is shown in the Table. Conclusions: Equivalence of C and T was observed for ORR in patients with HER2+ MBC in combination with P as first-line therapy. Secondary efficacy endpoints also supported the comparability between C and T. C was well tolerated with a safety profile comparable to that of T. Clinical trial information: NCT01084876. [Table: see text]
The importance of adjusting for treatment crossover bias in oncology clinical trials: An analysis of the EGF104900 trial in metastatic breast cancer (mBC).
Authors: Paracha Norman , Davies Andrew , Latimer Nicholas , Parker Christopher , Mealing Stuart , Scott David , Padhiar Amie , Schulpher Mark , Wang Qing
Published: March 2020

636

Background: EGF104900 is a phase III trial in mBC that compared lapatinib + trastuzumab (LAPTRZ, n=146) with LAP monotherapy (LAP, n=145). The trial allowed LAP subjects to switch to LAPTRZ on documented disease progression (following ≥4 weeks of LAP). Conventional intent-to-treat (ITT) analysis does not control for potential bias due to treatment crossover. The Rank Preserving Structural Failure Time Model (RPSFTM) estimates event times had patients not switched, and performs re-censoring. The approach preserves randomization and ordering of patients’ observed survival times, assuming that patients switching benefit from the treatment effect seen in those initially randomized to the treatment arm. The method is recognized by NICE, UK, as an appropriate method for adjusting for crossover bias. Methods: 53% of LAP subjects crossed over to LAPTRZ. Analyses were stratified by hormone receptor status and visceral/non-visceral disease. RPSFTM was implemented in Stata (using White’s strbee procedure). Absolute overall survival (OS) was estimated using a parametric survival distribution fitted to the trial data with/without crossover adjustment. The unadjusted ITT Cox hazard ratio (HR) was compared with the crossover adjusted RPSFTM estimate, and the absolute gain in OS evaluated. Results: Median OS in the LAPTRZ and LAP arms was 61 and 41 weeks, respectively (ITT HR 0.74, 95% CI: 0.56, 0.96); RPSFTM crossover-adjusted median OS for LAP was 32 weeks (RPSFTM HR 0.52; 95% CI: 0.29, 0.92). Mean OS for LAPTRZ was estimated under a Weibull distribution as 74 weeks, compared with 57 (ITT) and 44 (RPSFTM) weeks for LAP. Treatment with LAPTRZ was estimated to extend mean OS by 30 weeks controlling for treatment crossover using RPSFTM compared with 17 weeks by ITT. Conclusions: Oncology trials are often subject to treatment crossover. Controlling for potential treatment crossover bias can result in greater estimates of gain in OS compared with ITT analysis. In the context of mBC such differences are of great importance to patients, clinicians, and healthcare payers. Treatment crossover-analyses are therefore also important for estimating cost-effectiveness in oncology.
Biomarq: A novel approach to automated HER2-analysis of circulating tumor cells (CTCs).
Authors: Pestka Aurelia , Friedl Thomas W. P. , Majunke Leonie , Jaeger Bernadette , Andergassen Ulrich , Neugebauer Julia Katharina , Jueckstock Julia Kathrin , Keij Jan , Friese Klaus , Fehm Tanja N. , Mueller Volkmar , Janni Wolfgang , Rack Brigitte Kathrin
Published: March 2020

638

Background: Targeted treatment approaches directed against CTCs might improve the outcome of metastatic breast cancer patients. Accurate and reproducible assessment of the CTC phenotype is a requirement to use CTCs as treatment targets. The aim of this study was to test the suitability of the automated BioMarQ System (Veridex, USA) – an enhancement of the FDA-approved CellSearch System (Veridex USA) for CTC detection– for assessing the Her2-status of CTCs based on fluorescence and cell-morphology data. Methods: Data on classification of the Her2-status into four groups (0, +, ++, +++) obtained by visual inspection of CTCs after immunocytochemical staining with the CellSearch System, and of BioMarQ-generated automatic measures on fluorescence and cell morphology via image clips generated from raw images were available for 329 CTCs from 17 metastatic breast cancer patients. A discriminant analysis was performed to test whether linear combinations of the fluorescence and/or cell morphology measures allow a separation of CTCs into four groups according to the visual classification of their Her2-status. Results: The highest concordance with the visual classification was obtained by a set of three discriminant functions based on the five variables mean-, maximum- and integrated fluorescence intensity, cell area (µm2), and coefficient of variation for the pixel fluorescence values within a cell. All five variables differed significantly among the 17 patients (Kruskal-Wallis-test, all p < 0.001). Based on the three discriminant functions, 74.5% of all cases were correctly assigned to the four visually obtained categories (6 out of 8 CTCs classified as +++; 57 out of 80 as ++; 17 out of 65 as +, 165 out of 176 classified as 0). Conclusions: Our preliminary analysis shows that discriminant functions derived from measures on fluorescence and cell morphology generated by BioMarQ correctly assigned the Her2-status of CTCs to the four visually obtained categories in 75% of all cases. Further analysis based on a larger number of Her2-positive CTCs, and cross validation by FISH-analysis will provide deeper insight into the suitability of BioMarQ for objectively assessing the Her2-status of CTCs.
Exposure–safety relationship of trastuzumab emtansine (T-DM1) in patients with HER2-positive locally advanced or metastatic breast cancer (MBC).
Authors: Jin Jin , Wang Bei , Gao Yuying , Samant Meghna , Li Chunze , Song Chunyan , Swain Sandra M. , Untch Michael , Girish Sandhya
Published: March 2020

646

Background: Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate composed of trastuzumab, the cytotoxic agent DM1, and a stable thioether linker. The effects of T-DM1 exposure on safety in patients with HER2-positive locally advanced or MBC are reported. Methods: The exposure–safety analysis included 618 patients with pharmacokinetic (PK) data who received single-agent T-DM1 3.6 mg/kg q3w from five phase 2 or 3 studies: TDM4258g, TDM4374g, TDM4450g/BO21976, TDM4688g, and EMILIA. Exposure parameters observed in cycle 1 were T-DM1 conjugate AUC, T-DM1 conjugate Cmax, and DM1 Cmax, (no PK accumulation). Safety endpoints were worst grade of thrombocytopenia (TCP) or hepatotoxicity (HPT) by protocol definitions. A multivariate logistic regression analysis was conducted to evaluate the association of exposure and clinically relevant covariates with the probability of experiencing TCP or HPT. Platelet counts (PLT), alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (TBL) versus time profiles were also evaluated by exposure quartiles to further test exposure effect on lab values. A secondary analysis for patients in the EMILIA study alone (n=307) was also conducted. Results: Grade ≥3 TCP and grade≥ 3 HPT were observed in 72 patients and 45 patients in the exposure–safety data set, respectively. Data from the pooled studies showed no statistically significant association between exposure and the incidence of grade ≥3 TCP (T-DM1 AUC P=0.99, T-DM1 Cmax P=0.97, DM1 Cmax P=0.72), or grade ≥3 HPT (T-DM1 AUC P=0.25, T-DM1 Cmax P=0.93, DM1 Cmax P=0.95). Additionally, no obvious difference was observed for longitudinal PLT, ALT, AST, or TBL profiles across exposure quartiles, with no exposure–safety relationship for the probability that PLT, ALT, AST, or TBL exceeded grade 3 thresholds. Similar results were observed for the EMILIA analysis. Conclusions: For patients with HER2-positive locally advanced or MBC treated with T-DM1 3.6 mg/kg q3w, no exposure–safety relationship was observed for TCP, HPT, PLT, or liver function based on T-DM1 or DM1 exposure.
Augmenting state cancer registry data for quality-of-care assessment: A Georgia-based application to evaluate receipt of adjuvant therapies for breast cancer and colorectal cancer.
Authors: Lipscomb Joseph , Ward Kevin C. , Adams Kathleen , Joski Peter , Roblin Douglas , Gillespie Theresa Wicklin , Li Juan
Published: March 2020

6523

Background: The value of linking population-based cancer registry data with insurance claims files to assess quality of care has been demonstrated in numerous studies, including those using NCI’s linked SEER-Medicare database, covering patients age 65+ in fee-for-service plans, and studies linking registry data with Medicaid, private insurance, or managed care data covering the under-65 population. We describe a prototype program linking registry data with multiple data sources to assess quality of care for at-risk populations in a defined geographical area. Methods: Data exchange agreements were executed among the investigative site (Emory University), Georgia state government, and the claims data sources/vendors. We linked Georgia Cancer Registry (GCR) records for 1999-2005 incident cases of breast and colorectal cancer with enrollment and medical services records from Medicare, Medicaid, Kaiser Permanente of Georgia, and the State Health Benefit Plan (SHBP) which covers all state workers and dependents. Following data quality checks, algorithms based on National Quality Forum (NQF) endorsed breast and colorectal cancer quality measures were applied to each linked data set to assess performance. Results: The linked data sets included 60% of all breast and colorectal cancer cases in the GCR over the study period. Quality measure performance rates varied notably across payers. For example, the percent of Stage III colon cancer patients meeting the NQF standard for adjuvant chemotherapy in the linked GCR-Medicaid, GCR-Kaiser, and GCR-SHBP data were, respectively, 75%, 92%, and 92% (p<0.05). The rates for breast cancer patients meeting standards for adjuvant chemotherapy were 86%, 84%, and 87% (p=NS), respectively. Patients in the linked GCR-Medicare data (all age 65+) generally had lower performance rates for each NQF measure. Conclusions: Linking state cancer registry data with multiple public and private sources of administrative data is technically feasible, and may represent a viable strategy for building a national cancer data system for quality improvement, as recommended in 1999 by the Institute of Medicine.
Breast cancer patient surveillance following curative-intent treatment: Variation among metropolitan statistical areas.
Authors: Avino Robert J. , Allam Emad S. , Chen Ling , Virgo Katherine S. , Margenthaler Julie A. , Johnson Frank E.
Published: March 2020

6526

Background: There are about 3 million breast cancer survivors in the US, with about 230,000 new cases of breast cancer diagnosed annually. Most receive curative-intent treatment. Post-treatment surveillance is commonly done. We previously documented dramatic variation in surveillance intensity among ASCO experts. The only surveillance modalities endorsed by ASCO for asymptomatic patients are office visit and mammogram. We sought to determine the effect of the physician’s practice location on the intensity of surveillance by comparing Metropolitan Statistical Areas (MSAs). MSAs are large urbanized areas. Methods: The 3245 ASCO members who indicated that breast cancer was a major clinical focus of their practice were surveyed regarding their surveillance practices. They were asked to consider 4 idealized clinical vignettes and indicate their surveillance plan for each. A menu of 12 testing modalities was offered. Repeated-measures ANOVA was employed to compare practice patterns by MSA. Results: There were 1012 responses; 915 were evaluable. The modalities most frequently recommended were office visit, CBC, LFTs, and mammogram. We analyzed the 8 MSAs (New York, Chicago, Philadelphia, Los Angeles, Pittsburgh, Washington, Boston, and St. Louis) with enough responses for analysis. Every modality discouraged by ASCO was recommended by some respondents. Significant variation (p<0.05) in recommended frequency of use was present for all frequently recommended surveillance modalities. For example, in year 1, office visit was recommended 2.8 ± 0.9 (mean ±SD) times in Philadelphia and 4.0 ± 1.9 times in Los Angeles. Conclusions: Evidence-based clinical guidelines have proven effective in providing high quality care and decreasing variation in practice.ASCO members often recommend surveillance modalities that are not recommended by ASCO clinical guidelines, suggesting overuse. Statistically significant variation among the 8 MSAs in recommended use of most testing modalities was present. However, this variation was clinically quite small. Variation among MSAs cannot explain the known marked variation in clinical practice we have previously documented.
Impact of performance evaluation on the quality of care in non-small cell lung cancer.
Authors: Tanvetyanon Tawee , Lee Ji-Hyun , Fulp William J. , Jacobsen Paul B. ,   for the Florida Initiative for Quality Cancer Care
Published: March 2020

6531

Background: Improvement in the quality of care can translate into an improvement in the patient outcome. Evaluation of care quality among oncology practices has been associated with an improvement in the care of breast or colorectal cancer patients previously. Lung cancer is the leading cause of cancer death. Recently quality of care indicators specific for non-small cell lung cancer (NSCLC) have been developed. We investigated the impact of oncology practice evaluation on care quality in NSCLC. Methods: In 2008, members of the Florida Initiative for Quality Cancer Care submitted medical records of randomly sampled, new NSCLC patients who were seen in 2006 for review as baseline practice performance. Results were then circulated among members and voluntary improvement projects independently undertaken in each practice. In 2010, a repeat evaluation was conducted of new NSCLC patients first seen in 2009 to characterize change(s). Results: 10 practices (7 private and 3 university-based) contributed 1,091 patient records for analysis: 518 in 2006 and 573 in 2009. Baseline characteristics of patients were well balanced; however, the proportion of Medicaid or unfunded patients was higher in 2009 than in 2006 (14.8% vs. 7.7%, p=0.002). Of the 7 quality indicators measured, 4 showed a significant improvement when adjusted by practice site and patient characteristics (Table). Notable improvements included the use of brain staging before chemoradiation for stage III patients, performance status documentation and the use of cisplatin for adjuvant therapy. Conclusions: Performance evaluation is associated with an improvement in selected indicators of the quality of care in NSCLC. [Table: see text]
Cancer care coordination systematic review and meta-analysis: Twenty-two years of empirical studies.
Authors: Sheinfeld Gorin Sherri , Haggstrom David , Fairfield Kathleen , Han Paul , Krebs Paul , Clauser Steven B. ,   QCCC_CCI Working Group
Published: March 2020

6536

Background: To our knowledge, no systematic review of empirical papers describing cancer care coordination interventions has yet been conducted. The aim of this presentation is to describe the methods and findings from a systematic review and meta-analysis of all empirical papers describing cancer care coordination published between 1990-2012. Methods: Of 1241 abstracts collected from a search of PubMed and EMBASE, 108 studies were retrieved and reviewed; 49 were included in the systematic review. Each study had US or Canadian adult or child participants; each paper had comparison or control groups, measures, samples, and/or interventions. Two researchers independently applied a standardized search strategy, coding scheme, and on-line coding program to each study. Eight RCT’s met additional criteria for meta-analysis; a random effects estimation model was used for data analysis. Results: Among the 49 articles included in our systematic review, those that included implicit or explicit definitions of cancer care coordination described four components: (1) roles and models for communication and transfer of care between primary care physicians and oncologists during active treatment and survivorship; (2) care navigation through designated personnel or telecommunication processes among care team members; (3) treatment summaries and survivorship care plans; and (4) multidisciplinary communication accompanying patient and practice management within the framework of the Chronic Care Model (N=14). We found a medium-sized effect of cancer care coordination on care usage outcomes among the randomized clinical trials (e.g., reduced Emergency Department visits; g = 0.37 [95% CI = 0.29 - 0.44], I2= .000. Fail-safe N = 86). Conclusions: The findings from this current systematic review and meta-analysis will contribute to the evidence base on strategies that can improve the coordination of cancer care, particularly for patients with multiple chronic conditions, and thereby advance the goals of health care reform in the US.
What do patients with cancer think of the use of their tumor tissue for medical research?
Authors: Karapetis Christos Stelios , Kumar Rajiv , Timothy Quek , Sukumaran Shawgi , Kichenadasse Ganessan , Dua Divyanshu , Takhar Harminder Singh , Richards Alison , Mead Kelly , Ly Marleesa , Koczwara Bogda
Published: March 2020

6541

Background: Research involving archival tumor tissue has become increasingly important in molecular oncology and has led to improved therapeutics. There are important ethical considerations for such research. We examined the attitudes of patients with cancer toward research that used their tumor tissue. Methods: From January to April 2012, consecutive patients with cancer attending the outpatient clinic of the Flinders Cancer Centre were asked to complete a 27-item investigator-developed questionnaire. The questionnaire included 4 sections: 1) demographics, 2) understanding of cancer research, 3) donation of tumor tissue and 4) ethical issues. Results: 118 patients completed the questionnaire, 53% male and mean age 61. 95% stated that they believed that research involving tumor tissue was beneficial to the public and to cancer patients in the future. 72% responded such research could have a direct benefit for them. 94% would allow their tissue to be used for future research. 86% stated that nothing would prevent them from allowing tissue research. Only14% believed that they needed to be informed about the research. Only 5% were of the opinion that the tissue still belonged to them after it had been removed from their body. 72% were not concerned where their tissue was sent for research, whilst 19% preferred that the research be conducted in Australia. When asked about the use of tissue for research after death, 10% stated that their prior approval was required, less than 1% wanted their family members to approve the research whilst 80% felt that ethics committee approval without individual consent was acceptable. Less than 1% stated that the tissue should be destroyed after death. 69% expressed a preference for the research findings to be available to everyone without commercialisation. Conclusions: The majority of patients permit the use of their tumor tissue for research with ethical approval but without the expectation of individual consent. After death, most patients did not want to have their tissue discarded and were accepting of research without the need for prior consent or family approval. We need to understand the preferences of the majority of patients in determining optimal policy for correlative tumor tissue research.
Saving lives and costs through screening (Sc) for colorectal cancer (CRC): Implications for limited-resource healthcare systems (LRHS).
Authors: Barzi Afsaneh , Directo Michael , Dasu Sriram , Lenz Heinz-Josef , Sadeghi Sarmad
Published: March 2020

6545

Background: While USPSTF and ACP have determined that Sc for CRC is beneficial, the practice of Sc and its benefits are not established in LRHS caring for the uninsured. We tested the hypothesis that Sc could result in a reduction in the therapy (Tx) costs for CRC and offset Sc costs. Methods: Using a Markov model we performed individual level microsimulations (ILMS) of 100,000 subjects ≥ 50 years with average risk of CRC. Five Sc strategies (ST) were tested: Fecal occult blood (FOBT) and fecal immune chemical (FIT) annually and biannually (FOBT2, FIT2), and colonoscopy (CS) every 10 years. No Sc was used as referent ST (Ref). Compliance with Sc was assumed at 16% for FOBT and FIT and 56% for CS. Sc was offered to 100, 50 and 25% of the subjects in 3 separate ILMS. Life Years Gained (LYG) and Incremental Cost Effectiveness Ratios (ICER) were calculated. Costs and LYG discounted at 3%. Results: Mean follow up: 12.6 years. At all coverage levels all STs resulted in decreased CRC costs by 9-17% and deaths by 14-41%. CS decreases CRC incidence by 5-26%. At higher coverage rates, CS remains the best ST, but at 25% and lower coverage FOBT and FIT function better. Conclusions: These data support systematic use of Sc for CRC in LRHS. Until resources for CS are available, lives and costs could be saved by simple measures such as FOBT and FIT and enrolling as few as 4,552 subjects. [Table: see text]
Racial disparities in initiation of endocrine therapy for early-stage breast cancer.
Authors: Reeder-Hayes Katherine Elizabeth , Meyer Anne-Marie , Dusetzina Stacie , Liu Huan , Wheeler Stephanie B.
Published: March 2020

6572

Background: Oral endocrine therapy (ET) is the cornerstone of adjuvant therapy for hormone receptor-positive (HR+) breast cancer, greatly reducing the risk of recurrence and death when taken for at least 5 years. Failure to initiate ET is a known problem that adversely affects recurrence and survival. The survival gap between black and white women with breast cancer is most pronounced in HR+ subtypes, and could be related to differences in ET use. The relationship between race and failure to initiate ET is not well defined. We investigated patterns of ET initiation by race in a diverse cohort of women covered by commercial health insurance. Methods: We identified 2753 women with incident HR+ breast cancer in the North Carolina Central Cancer Registry whose records linked to insurance claims using the statewide Integrated Cancer Information and Surveillance System (ICISS) database maintained by the University of North Carolina. The sample included privately insured women age <65 years who were diagnosed with stage I-III HR+ breast cancer between 2004 and 2009 and received primary therapy including breast surgery within 12 months of diagnosis. We used multivariate Poisson regression with robust variance to examine the effect of race on likelihood of initiating ET (tamoxifen, anastrozole, letrozole or exemestane). Results: 14% of eligible women did not initiate any form of ET within 12 months of diagnosis. Black women initiated ET at a significantly lower rate (IRR 0.83, 95% CI 0.73-0.93) after adjustment for age, disease characteristics, other treatments, and socioeconomic variables. Women receiving breast conserving surgery (BCS) without radiation (RT) were less likely to initiate compared to those receiving BCS + RT or mastectomy, and women whose treatment included chemotherapy were less likely to initiate ET. Conclusions: Black women in our sample were significantly less likely to initiate ET in a timely fashion than their white counterparts. This underutilization may contribute to the pronounced survival gap among black women with HR+ breast cancer, and represents an opportunity for intervention to reduce breast cancer disparities. Further investigation is needed to understand the reasons why black women do not initiate ET.
Minimal clinically important difference (MCID) for the functional assessment of cancer therapy: Cognitive function (FACT-Cog) in breast cancer patients.
Authors: Chan Alexandre , Foo Yu Lee , Ham Guo Maung Shwe , Kee Yuan Chuan , Tan Yee Pin , Yong Wei Sean , Madhukumar Preetha , Ooi Wei Seong , Chay Wen Yee , Dent Rebecca Alexandra , Ang Soo Fan , Lo Soo Kien , Yap Yoon Sim , Ng Raymond C.H. , Cheung Yin Ting
Published: March 2020

6589

Background: Establishing the Minimal Clinically Important Difference (MCID) is essential for interpreting the clinical relevance of patient reported outcomes. This is the first study to date to determine the MCID of FACT-Cog, a 37-item validated subjective neuropsychological instrument designed to evaluate cancer patients’ perceived cognitive deterioration on their quality of life. Methods: This prospective, observational study involved 220 breast cancer patients who have completed FACT-Cog and EORTC-QLQ-C30 at two time points: baseline and at least 3 months following chemotherapy. The MCID was computed using 3 approaches: 1) an anchor-based approach utilized the validated EORTC-QLQ-C30-Cognitive Functioning scale (CF) as the anchor for patients who showed a minimal deterioration on the CF (defined as a one-step deterioration on the CF scale); 2) a Receiver Operating Characteristic (ROC) curve was used to identify an optimal MCID cut-off point for deterioration; 3) a distribution-based approach utilized the 0.33 SD, 0.5 SD and one standard error of measurement (SEM) of the total FACT-Cog score (148 points) to estimate the MCID. Results: There was moderate correlation between the mean change scores of FACT-Cog and CF (rp= 0.43, p<0.001). The CF-anchored MCID was 9.6 points (95% CI 4.4 - 14.8). MCID derived from the ROC method was 7.5 points (AUC: 0.75; sensitivity: 75.6%; specificity: 68.8%). Using the distribution-based approach, MCID corresponding to effect sizes of 0.33SD to 0.5SD of the total FACT-Cog score ranged from 6.9 – 10.3 points and one-SEM criterion resulted in a MCID estimate of 10.6 points. Combining results from all approaches, the MCID identified for FACT-Cog ranged from 6.9 – 10.6 points (4.7% to 7.2% of total score). Conclusions: A 6.9 to 10.6 points reduction of the FACT-Cog score corresponds to the smallest clinically-relevant perceived cognitive deterioration. These estimates are important as they can facilitate the interpretation of patient-reported cognitive changes and sample size estimation in future studies.
Effect of female-dominant support networks on end-of-life decision making among women with advanced or recurrent cancer.
Authors: Robison Katina , Stuckey Ashley , Dizon Don S. , Rogers Michelle , Ott Miles , Miller Susan , Politi Mary C. , Clark Melissa
Published: March 2020

6590

Background: Improved understanding of the factors that influence a woman’s end of life (EOL) decisions while confronting cancer is needed. The objective of this study was to determine if the composition of one’s social network was associated with advance care planning (ACP) among women with metastatic or recurrent gynecologic or breast cancer. Methods: Women were recruited from a program in women’s oncology in the northeast. Women with an established diagnosis of recurrent or metastatic cancer for ≥3 months duration were eligible. We asked women with advanced or recurrent cancer about their support networks and end-of-life decisions. Interviews were conducted by research staff. Clinical characteristics and documentation of EOL decisions of enrolled women were obtained through chart reviews. Multivariable logistic models were computed. The study protocol was approved by the hospital and university Institutional Review Boards. Results: 200 women were enrolled in the study. The majority had gynecologic malignancies (65.5%). Older age was associated with having an advanced directive (AD) (p<.0001) and a health care proxy (HCP) (p=0.002). Additionally, having more females than males in one’s support network was associated with an AD (p=0.005) and a HCP (p=0.012). Women with gynecologic cancer were more likely to self-report a HCP compared to those with breast cancer (p=0.040).A female support person was 1.57 times more likely to be trusted to make a medical decision (p=0.002) and a female support person was 1.33 times more likely to be someone a woman spoke with about her end of life decision than a male support person (p=0.037). Neither naming a HCP or having an AD were associated with number of support persons named, total number of female support persons, number of friends, number of children, or presence of an intimate partner. Conclusions: Women with more females than males in their social network were more likely to have an advance care directive or health care proxy. In addition, women were more likely to trust and talk with a female support person about end of life decisions than a male support person. However, the composition of the network was not associated with the likelihood of having completed ACP.
Human resources allocation in oncologic day hospital: Validation of the Kohen-Gil Deza scale (KGD) for risk assesment.
Authors: Kohen Nelson , Gil Deza Ernesto , Gercovich Natasha , Morgenfeld Eduardo L. , Garcia Gerardi Carlos Fernando , Martin Reinas Gaston , Montiel Monica , Tognelli Flavio , Rivarola Edgardo G. J. , Gercovich Felipe G.
Published: March 2020

6596

Background: The oncological day hospital (ODH) at IOHM carries out 80 chemotherapies per day with 6 certified oncological nurses as staff. Human resources allocation in oncology has not been formally studied in relation to treatment risks. The objective of this paper is to present a risk assessment model for the rational allocation for human resources in the ODH using the KGD scale. Methods: The KGD scale was designed through a retrospective evaluation of more than 15,000 treatments (Tx). Between November 1st and December 1st, 2012, this instrument was validated with all new patients (Pt) beginning Tx at IOHM. The KGD scale evaluates risk according to: Five Pt characteristics (Elderly, Polymedicated, Without symptom control, Neuropsychiatric problems, Presence or absence of family members); Four Tx characteristics (New drugs, Complex protocol, High risk of acute toxicity, Infrequently used) and workplace context(New personnel, Holiday absences, With or without close medical support). The KGD scale was determined for each Tx and applied as follows: Low Risk (0-3 points): two nurses in the ODH, supervision is at the patient’s request and the chemotherapy can be administered at the beginning or end of the workday; Intermediate Risk (4-5 points): three nurses in the ODH, supervision is mandatory and the treatment can take place at any time in the workday; High Risk(6 or more points): four nurses in the ODH, supervision must be constant and the Tx must take place in the middle of the workday. The chemotherapy outcome was observed. Results: One hundred and thirty patients were admitted. Sex fem 74 (59%), male 56 (41%): age: 49y (range 22-87). Diagnosis: breast 40, colon: 21, lung: 16, ovaries:11, lymphoma: 11, testis:7, sarcoma: 5 ; others: 19 KGD risk assessment: Low Risk 25 pts (19 %); Intermediate Risk 77 pts (59%); High Risk 28 pts (21%). There were no complications in any of the 312 chemotherapy treatments administered to this cohort. Conclusions: 1) The KGD scale has shown to be a useful aid in the treatment risk assessment. 2) Use of the KGD scale allows for an efficient personnel allocation at the ODH according the Tx risk 3) The academic qualification of the nurses staff are mandatory to control the risk.