bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival and prognostic factors of radioiodine refractory pulmonary metastatic differentiated thyroid carcinoma (DTC).
Authors: Wassermann Johanna , Bernier Marie-Odile , Spano Jean-Philippe , Lepoutre-Lussey Charlotte , Simon Jean-Marc , Ménégaux Fabrice , Hoang Catherine , Aurengo André , Leenhardt Laurence
Published: March 2020

6093

Background: The challenging key point of management of radioiodine refractory DTC patients is to define those who could benefit from experimental drugs in clinical trials. Methods: We reviewed clinical and pathological data of patients with refractory pulmonary metastatic DTC treated in our center from 1990 to 2011. Survival was estimated with the method of Kaplan-Meier. Associated prognostic factors were studied in Cox model based analyses. Results: Among 167 pulmonary metastatic DTC, 46% (n=76) met a criterion of radioiodine refractory disease: at least one metastases without I131 uptake: 61% (n=46); progressive disease despite I131: 22% (n=17) and absence of complete response despite a cumulated dose >600mCi: 17% (n=13). There were 63% of female (n=48) and the median age was 64 years (range 18-87). The initial treatment was total thyroidectomy in 92% (n=70), lymph node dissection in 71%, (n=54) and radioiodine therapy in 100% of patients. Pathological features were papillary histology in 61% (n=46), follicular histology in 29% (n=22) and poor differentiated histology in 10% (n=8). pT stage was 1ab, 2, 3, and 4 in 11%, 13%, 63% and 13% respectively, pN stage after lymph node dissection was 0, 1a and 1b in 33%, 7% and 60% respectively. Metastasis were present at diagnosis in 45% (n=34) of cases. The refractory feature was established at the time of diagnosis and in the follow-up in 18% and 82% of cases respectively. When the disease was considered as refractory, the median overall survival was 5.5 years. The refractory feature at the initial diagnosis was the only independent prognostic factor correlated with poor survival (p<0.001). Conclusions: Patients who are considered as radioiodine refractory at the initial diagnosis of DTC have poor prognosis and should be considered for clinical trials in case of progression.
Safety of trastuzumab in HER2-positive primary breast cancer in Japan: Initial safety report for the large-scale cohort study (JBCRG C-01).
Authors: Yamamoto Naohito , Yamashiro Hiroyasu , Iwata Hiroji , Masuda Norikazu , Ohtani Shoichiro , Takahashi Masato , Yamazaki Kosuke , Kato Makoto , Ohno Shinji , Kuroi Katsumasa , Yamagami Kazuhiko , Morimoto Takashi , Hasegawa Yoshie , Takano Toshimi , Kadoya Takayuki , Hosoda Mitsuchika , Abe Hajime , Morita Satoshi , Yasuno Shinji , Toi Masakazu
Published: March 2020

613

Background: The global randomized trials with trastuzumab (H) shows increased cardiotoxicity in patients (pts) with HER2 positive early breast cancer (BC). Safety in Japanese has not been fully evaluated. We evaluated the safety, especially focused on cardiotoxicity, of H adjuvant (adj) therapy in an observational study in Japan (UMIN000002737). Methods: Pts with histopathologically confirmed HER2 positive invasive BC were registered. Women with stage I-IIIC disease who received H as neo-adj and/or adj therapy were eligible. Mean LVEF at 3, 6, 9 and 18 months (M) was evaluated. The time points represent examination on day 60-120, 150-210, 240-330 and 455-635, respectively. Results: A total of 2024 pts were registered from 56 institutes between July 2009 and June 2011. Data of 1875 pts were collected and finalized by September 2012, and 1800 of them were analyzed for safety. The median follow-up was 35 M. The mean age was 54.5 years. Elderly pts ≥60 years were 32.7%. Treatments after surgery were: concurrent chemotherapy (CT) and H in 20.1%, sequential CT and H in 43.5% and H monotherapy in 35.9%. Adverse events (AEs) associated with H were reported in 350 pts (19.4%) and grade (G) 3/4 AEs in 12 pts (0.7%). G 3/4 cardiotoxicity was reported in 7 pts (dysfunction, 4pts; angina, 1 pt; myocardial infarction, 1 pt and heart failure, 1 pt). The mean LVEF at the baseline was 69.4%. Mean LVEF at 3, 6, 9 and 18M were 66.9%, 66.3%, 65.3% and 66.3%, respectively. Compared to the baseline, LVEF decreased with significant difference at all time points (p<0.0001). LVEF decrease ≥10% occurred in 177 pts (during H treatment,130 and after H treatment, 47). Follow-up data were available in 66 pts: 34 pts recovered to the baseline. Mean time to recover was 262 days. The univariate analysis showed using anthracycline (odds ratio 2.312, p=0.003) was the only risk factor for cardiotoxicity. However, elderly, radiation concurrent/sequential treatment with CT and H had no impact. Conclusions: From our study, we found the AE profiles of H were consistent with previously known AEs. We found using anthracycline was the risk factor for cardiotoxicity at the moment. We should carefully follow pts and watch long-term safety. Clinical trial information: 000002737.
Cardiac toxicity in breast cancer patients treated with dual HER2 blockade: A meta-analysis of randomized evidence.
Authors: Valachis Antonis , Nearchou Andreas Demetrios , Polyzos Nikolaos P. , Lind Pehr
Published: March 2020

624

Background: The dual antiHER2 blockade has been shown promising results in patients with HER2-positive breast cancer. Whether this treatment strategy jeopardizes the risk for cardiac adverse events is unclear. We conducted a meta-analysis of randomized trials to investigate the risk of cardiac adverse events when a combination of anti-HER2 therapies is used. Methods: We searched Medline, the Cochrane library, as long as the electronic abstract databases of the major international congresses’ proceedings to identify randomized trials that evaluated the administration of anti-HER2 monotherapy (lapatinib or trastuzumab or pertuzumab) versus anti-HER2 combination therapy with or without chemotherapy in breast cancer. Study outcomes were the congestive heart failure (CHF) grade >/= 3 and left ventricular ejection fraction (LVEF) decline < 50% or more than 10% from baseline. We calculated pooled odds ratios (ORs) and 95% Confidence Intervals (CI) with the Peto method. Results: Six trials were considered eligible. Overall incidence results for CHF in the combined antiHER2 therapy and the antiHER2 monotherapy were 0.88 % (95% CI: 0.47% - 1.64%) and 1.49 % (95% CI: 0.98% - 2.23%). The incidence of LVEF decline was 3.1 % (95% CI: 2.2% – 4.4%) and 2.9% (95% CI: 2.1% - 4.1%) respectively. The OR of CHF was 0.58 (95% CI: 0.26-1.27, p-value= 0.17) while the OR of LVEF decline was 0.88 (95% CI: 0.53-1.48, p-value= 0.64). In subgroup analyses, there were no significant differences in CHF or LVEF decline among different treatment settings or types of antiHER2 therapy. Conclusions: This meta-analysis offers substantial randomized evidence from trials with well-defined cardiac evaluations that a dual anti-HER2 therapeutic approach does not increase the risk for cardiac toxicity.
Utility of 2D-speckle tracking echocardiography in early identification of left ventricular dysfunction in antineoplastic therapy-induced cardiotoxicity.
Authors: Coppola Carmela , Tocchetti Carlo G. , Piscopo Giovanna , Cipresso Clemente , Maurea Carlo , Lombari Maria Cristina , Rea Domenica , Maiolino Piera , Monti Maria Gaia , Tarantini Luigi , Russo Giulia , Cioffi Giovanni , Giotta Francesco , Oliva Stefano , Capasso Immacolata , Iaffaioli Rosario Vincenz , Arra Claudio , Maurea Nicola
Published: March 2020

631

Background: ErbB2 is overexpressed in about 25% of breast cancers; in the heart, it modulates myocardial development and function. Trastuzumab (T), an anti-ErbB2 inhibitor, has improved the prognosis of patients with breast cancer, but is related to an increased risk of asymptomatic left ventricular (LV) dysfunction (3-34%) and heart failure (2-4%). Conventional measures of ventricular function, such as fractional shortening (FS) and ejection fraction (FE) are insensitive in detecting early cardiomyopathy induced by antineoplastic therapy. Aim of this study is to evaluate whether myocardial strain by 2D-speckle tracking (ST) is able to identify early LV dysfunction in mice treated with doxorubicin (D) and T, alone or in combination (D+T) and to relate data of cardiac function with tissue alterations. Methods: Cardiac function was measured with FS, by M-mode echocardiography, and with radial myocardial strain with ST in sedated C57BL/6 mice (8-10 wk old) at time 0, 2 and 6 days of daily administration of D, T, D+T and in a control group. In excised hearts, we evaluated TNFα and CD68 by immunohistochemistry; interstizial fibrosis was analyzed with picrosirius red staining. Results: FS was reduced in group D and D+T at 2 days (52+0.2% and 49+2% respectively), both p<0.001 vs 60+0.4% (sham), while in group T it decreased only at 6 days (49+1.5% vs 60+0.5%, p=.002). In contrast, after 2 days, myocardial strain was already reduced not only in D and D+T, but also in T alone: 43+3%, 49+1%, and 44+7%, respectively, all p<0.05 vs sham (66+0.6%). Cardiotoxicity was associated with significant alterations in extracellular matrix remodeling as confirmed by an increase of interstizial collagen with D (4.56%), T (2.17%) and D+T (3.77%)at 6 days p<0.05 vs sham (1.17%) and by increased cardiac inflammation in fact the myocytes were positive for TNFα and CD68 cells/mm2at 6 days in group D (16.46% and 155 respectively), in group T+D (12.35% and 74.16) and in group T (5.65% and 72.32) p<0.01 vs sham (0.56% and 2.3). Conclusions: Myocardial strain identifies LV systolic dysfunction earlier than conventional echocardiography and can be a useful tool to predict cardiotoxicity in this setting.
Identification of patients at high risk of recurrent disease development by detection of HER2-positive disseminated tumor cells in bone marrow of patients with HER2-negative tumors.
Authors: Aft Rebecca , Mudalagiriyappa Chidananda , Pillai Sreeraj , Trinkaus Kathryn , Fleming Timothy , Watson Mark
Published: March 2020

633

Background: A subpopulation of patients with HER2-negative tumors benefit from HER2 therapy. HER2 expression can be discordant between primary tumors and metastases. We have examined the bone marrow (BM) of early stage breast cancer patients for HER2-expression by disseminated tumor cells (DTCs) and the association with disease recurrence. Methods: BM was collected from clinical stage II-III breast cancer prior to treatment between 2007-2011. Gene expression of ERBB2 was determined by multiplex PCR (Fluidigm Biomark [FB]). Positive expression was defined as at least 1.4 fold above a pool of normal BM. Expression was confirmed by single gene PCR and Nanostring nCounter (NC) assays. Cox proportional model was used to estimate hazard ratios (HR). Results: BM from 74 patients was analyzed. Median follow-up was 3.4 years (range 8 months-84 months). 24% of the patients developed metastatic disease. For ERBB2 detection, there was excellent correlation between NC and the FB assays (kappa=0.87, 95% CI [0.62, 1.00]). Nine patients expressed ERBB2 in their BM. Five of the 9 patients had Her2-positive tumors and were treated with trastuzumab. One of 5 (20%) of these patients relapsed whereas 75% (3 of 4) of the patients with HER2-negative tumors but ERBB2-positive DTCs relapsed. Patients with HER2-negative tumors/ERBB2-positive BM were found to have a greater hazard of recurrence than patients with HER2-negative tumors/ERBB2-negative BM or ERBB2-positive DTCs treated with trastuzumab (p=.0069; Table). Those patients with ERBB2-positive BM who did not receive trastuzumab had a decreased disease free survival (p=.016). Conclusions: We have found discordant expression of HER2/ERBB2 in tumors and BM of stage II-III breast cancer patients. The presence of ERBB2 expressing DTCs in patients with HER2-negative tumors identifies a subset of patients at increased risk of recurrence who may benefit from targeted HER2-therapy. [Table: see text] .
A Bayesian meta-analysis of the prognostic value of circulating HER2/neu levels in breast cancer (BC) patients.
Authors: Carney Walter P. , Thiel Robert , Bernhardt Dirk , Ali Suhail M. , Leitzel Kim , Lipton Allan
Published: March 2020

643

Background: Many reports have shown the prognostic value of HER-2 measured in tumor tissue or in blood. In 2009, Finn et.al. showed that in a study of 579 MBC patients whose serum HER-2 levels (sHER-2) were constantly below normal had a longer PFS than patients with a sHER-2 level constantly above normal. Patients who converted from above normal to less than normal during therapy had a longer PFS than the opposite change. Methods: We performed a Bayesian meta-analysis of 12 studies where all sHER-2 levels were measured using an FDA cleared sHER-2 test with a standard cutoff of 15ng/ml. We chose a Bayesian approach because a “meta-analysis” is a natural extension of the Bayesian view that current knowledge is the result of prior knowledge modified by the data. After an in depth literature search, we selected 12 publications based on the following criteria. Baseline levels were available from either early stage or late stage patients who had at least a 2 year disease free or progression free survival as indicated by a Kaplan-Meier (K-M) curve. Results: The analysis included 4030 BC patients of which 1106 patients had baseline levels < 15ng/ml and 2924 patients had baseline values >15ng/ml. From the K-M curves, we estimated the number of recurrences up to 24 months in each group and prepared a 2x2 table for each study. We determined the odds ratio (OR) for the 12 studies which ranged from 0.57 to 74. A posterior distribution for the aggregated 12 studies can be represented by a Dirichlet distribution. 10,000 estimates of the aggregated OR indicated that there is a 95% credibility that the odds of a woman with baseline sHER-2 >15ng/ml recurring at or before two years is between 3.39 and 4.57 times higher than the odds of a woman whose baseline sHER-2 was < 15ng/ml recurring at or before two years. Conclusions: This meta-analysis agrees with previous studies that serum HER-2 levels > 15ng/ml can be a strong prognostic indicator for women with Breast Cancer and that managing therapy regimens to maximize the decrease in serum HER-2 levels could be important target in treating patients.
Exposure–efficacy relationship of trastuzumab emtansine (T-DM1) in EMILIA, a phase III study of T-DM1 versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC).
Authors: Wang Bei , Jin Jin , Wada Russell , Fang Liang , Lu Dan , Guardino Ellie , Swain Sandra M. , Untch Michael , Girish Sandhya
Published: March 2020

644

Background: T-DM1 is an antibody–drug conjugate composed of trastuzumab (T), a stable thioether linker, and the potent cytotoxic agent DM1. In the phase III study EMILIA, median PFS and OS were significantly prolonged with T-DM1 vs XL in patients (pts) with HER2-positive locally advanced or MBC previously treated with T and a taxane; (PFS hazard ratio [HR]=0.65, p<0.001; OS HR=0.68, p<0.001). We report the effects of T-DM1 exposure on efficacy outcomes in EMILIA. Methods: In EMILIA, pts were randomized 1:1 to receive T-DM1 3.6 mg/kg q3w (n=495) or XL (n=496) in 21-day cycles. Pharmacokinetic (PK) samples were from cycle 1 (n=350, T-DM1 arm only). Exposure variables were T-DM1 AUC, T-DM1 Cmin, total T AUC, and DM1 Cmaxcalculated by noncompartmental analysis. A logistic regression model was used to evaluate the relationship between T-DM1 exposure and objective response rates (ORR) in the T-DM1 arm. Multivariate Cox proportional hazards models were used to calculate HRs of OS and PFS for each T-DM1 exposure quartile vs all randomized pts in the XL arm, adjusting for baseline covariates. Results: For ORR, mean T-DM1 AUC was 536 day*ug/mL for responders and 502 day*ug/mL for non-responders (P=0.09); mean DM1 Cmax was 4.55 ng/mL and 4.64 ng/mL, respectively (P=0.64). OS and PFS HRs (and 95% CIs) of T-DM1 vs XL stratified by T-DM1 exposure quartiles are shown (Table). Conclusions: In EMILIA, no clear trends were observed between T-DM1 exposure and PFS, OS, or ORR, following administration of T-DM1 3.6 mg/kg q3w. However, there was a suggestion of improved OS HR by stratified T-DM1 Cmin quartiles, albeit with mostly overlapping 95% CIs. Ongoing T-DM1 clinical trials will further evaluate this potential relationship. [Table: see text]
Impact of copayment elimination on annual and biennial screening mammography utilization among rural U.S. women.
Authors: Peppercorn Jeffrey M. , Wheeler Stephanie B. , Houck Kevin , Peterson Bercedis , Villagra Victor , Antetomaso James , Wogu Adane Fekadu , Lyman Gary H.
Published: March 2020

6503

Background: Early detection of breast cancer through mammography screening leads to earlier stage at diagnosis and improved survival. Previous research has shown that rural American women are less likely to receive screening mammography compared to their urban counterparts. Copayments for mammography are a potential barrier to screening, and elimination of copayments may improve screening rates. We examined annual (aSMU) and biennial (bSMU) screening mammography utilization and the impact of copayment elimination among rural U.S. women. Methods: Using the insurance claims database of the National Rural Electric Cooperative Association (NRECA), which insures over 100,000 electrical workers and their families nationally, we identified all women ages 40 to 64 with no prior history of invasive breast cancer or DCIS (based on ICD-9 codes) and captured claims for aSMU and bSMU between 1999 and 2009. Changes in screening over time were assessed for the periods before and after NRECA elimination of copayments for screening mammography in January, 2006. Chi-squared tests were used to compare aSMU and bSMU rates by age group. All p-values are two-sided. Results: During this time period, over 20,000 women ages 40 to 64 received health insurance through NRECA each year. From 1999 to 2009, aSMU increased from 38.1% to 49.5%, while bSMU increased from 57.2% to 68.1%. Screening increased significantly following elimination of copayments in 2006 (p = 0.0004). Specifically, for the period 2006-2007 compared to 2004-2005, the percentage of women undergoing at least biennial screening increased from 60.9 to 68.8% (p < 0.0001), with absolute differences in screening by age ranging from an increase of 5.3% among women 40-45, to 10% among women 60 – 64. Conclusions: Evaluation of insurance claims data from rural US populations reveals that a large percentage of rural women ages 40 to 64 do not undergo even biennial breast cancer screening. Elimination of copayments improves both annual and biennial screening rates in all age groups, but does not eliminate all barriers. Further investigation is ongoing to understand financial and non-financial barriers to screening and attitudes towards current screening recommendations.
Accuracy and completeness of diagnosis codes for cancer metastasis on Medicare claims.
Authors: Chawla Neetu , Yabroff K. Robin , Mariotto Angela , McNeel Timothy S. , Schrag Deborah , Warren Joan L
Published: March 2020

6521

Background: Researchers are increasingly using diagnosis codes from administrative claims for cancer patients to identify metastatic disease at initial diagnosis or recurrence. However, the validity of metastasis codes on claims has not been established. We used the linked SEER -Medicare data to assess the completeness and validity of metastasis codes from Medicare claims for three common U.S. cancers. Methods: The study included 80,052 breast, lung, and colorectal cancer patients diagnosed with localized, regional, or distant disease in the SEER data between January 1, 2005 and December 31, 2007. From Medicare claims, patients were classified as having regional or distant disease at diagnosis if they had one hospital claim or two physician claims with metastasis codes within 3 months of diagnosis. Patients without claims with metastases codes were classified as having local disease. Using SEER data as the gold standard, we calculated sensitivity, specificity, positive and negative predictive values of metastasis codes on Medicare claims. We conducted multivariate logistic regression analysis to evaluate patient factors associated with stage misclassification for each cancer site. Results: For patients with distant disease per SEER data, the sensitivity and PPV of the claims to identify distant disease was: breast (50.6%, 67.3%), colorectal (72.2%, 68.8%) and lung cancer (42.1%, 88.6%). None of the measures for stage simultaneously exceeded 80% for sensitivity, specificity, and PPV for any of the cancer sites. In adjusted analysis, older, lower-income, and African American patients were more likely to have stage at diagnosis misclassified from Medicare claims. Conclusions: Use of diagnosis codes alone in Medicare claims will misclassify stage at diagnosis for cancer patients, particularly for patients with metastatic disease. Our findings also suggest that using diagnosis codes for metastasis to define recurrence in Medicare claims will be limited.
Black-white disparity in physical performance among older women with breast cancer: The role of physical activity and inflammation.
Authors: Owusu Cynthia , Schluchter Mark D. , Koroukian Siran M. , Schmitz Kathryn , Berger Nathan A.
Published: March 2020

6525

Background: Compared with non-Hispanic Whites (NHW), African-Americans (AA) experience poorer physical function. However, little is known about the existence of racial disparity in physical performance among older adults with cancer, and clinical factors that might explain such differences. Methods: This is a cross-sectional study of women ≥ 65 years (n=108), with stage I-III breast cancer. Before adjuvant treatment, participants completed the Short Physical Performance Battery (SPPB), an objective measure of lower extremity function on a scale of 0-12, with higher scores denoting higher physical performance. Self-reported physical activity was ascertained with the Minnesota Leisure Time Activity Questionnaire. Serum level of C-reactive protein (CRP) was determined and log transformed for analyses. Results: The median age was 74.0 years (range 65-93 years) and 32% were AA. The mean SPPB score was 8.5 (SD 3.5). Compared to NHW, AA had lower mean SPPB scores (7.0 vs. 9.2, p=0.002), were less physically active (8.2 vs. 19.4 MET-hours/week, p=0.005), and had higher mean serum CRP(log) (-0.43 vs. -0.86, p=0.002). In multivariate linear regression analysis that accounted for age, educational status, comorbidities and geriatric syndromes, AA race relative to NHW was independently associated with decreasing SPPB scores, [beta coefficient = -1.67, SE: 0.57, p=0.004]. When differences in serum CRP and physical activity were accounted for in the model, increasing CRP and decreasing physical activity were independently associated with decreasing SPPB scores, and eliminated the racial difference in physical performance by 23% and 40%, respectively. This suggests sub-clinical inflammation and physical activity mediate the relationship between race and physical performance. Conclusions: Among older women with breast cancer, racial disparity in physical performance may be reduced through increased physical activity and therapeutic strategies that moderate sub-clinical inflammation. Given the clinical importance of functional status in cancer treatment decision-making, interventions directed at attenuating racial disparity in physical performance are warranted.
The role of families in decisions about cancer treatments.
Authors: Soriano Gabriela , Landrum Mary Beth , Weeks Jane C. , Arora Neeraj K , Malin Jennifer , Ganz Patricia A. , van Ryn Michelle , Keating Nancy Lynn
Published: March 2020

6528

Background: Shared decision-making is an important component of patient-centered care and is associated with improved health outcomes. Little is known about patients’ involvement of family members in decisions about cancer treatments or whether family involvement varies by patient demographic or clinical characteristics. Methods: Data for this study were collected as part of the Cancer Care Outcomes Research and Surveillance (CanCORS) study, a large multi-regional prospective cohort study of cancer care and outcomes of lung and colorectal cancer patients. Patients were surveyed about the roles of their families in decisions about surgery, radiation, and/or chemotherapy. We used multinomial logistic regression to identify patient factors independently associated with family roles in decisions. Results: Among 5284 patients, 28.5% reported little or no family input in decisions, 22.1% reported making decisions after considering the family’s opinion, 47.9% reported the patient and family made decisions together, and 1.5% reported the family made decisions. In adjusted analyses, married, female, older, and insured patients were more likely to report making decisions with their family (all P<.001). Family involvement varied substantially by race/ethnicity and language, with Chinese-speaking Asian (63.5%) and Spanish-speaking Hispanic (56.8%) patients reporting making decisions with their family more often than English-speaking Hispanic patients (48.5%) and whites (48.3%). Patients from Veterans Affairs hospitals were least likely to report making decisions together with family (P<.001). Family involvement varied statistically by cancer type, stage, comorbidity, health status, and depression, but differences were minimal. Conclusions: Most patients with a new diagnosis of lung or colorectal cancer involve family members in treatment decisions. Certain groups, such as non-English speaking Hispanics and Asians rely significantly on family; for these groups, it is important that physicians inquire about patients’ preferences for family involvement and work to integrate family members in decisions accordingly. Further studies are needed to determine the impact of family involvement in treatment decisions on oncology outcomes.
Geographic variation in the adjuvant treatment of NSCLC over time.
Authors: Schroeder Mary C. , Tien Yu-Yu , Halfdanarson Thorvardur Ragnar , Abu Hejleh Taher , Nattinger Matthew , Brooks John
Published: March 2020

6542

Background: Adjuvant chemotherapy (ACT) and postoperative radiotherapy (PORT) are used in the treatment of resected NSCLC to reduce risk of relapse, but guideline-based recommendations for these treatment modalities have varied over time. ACT is now recommended for stage II-IIIA NSCLC following resection based on phase III trial results which, starting in 2003, showed improved survival. Conversely PORT recommendations have been rescinded due largely to a 1998 Lancet meta-analysis. In this study we explore the rates of these two adjuvant treatment modalities across areas over time. Methods: Using SEER-Medicare data we identified 18,410 patients diagnosed 1992-2007 with resected NSCLC. Adjuvant treatment was defined as the first treatment received within 4 months of surgery. The study period was divided into 3 eras: 1992-1998, 1999-2003, and 2004-2007. Area treatment rates were calculated using the 50 patients closest to each zip code, adjusting for patient and area characteristics. Areas were then ranked and divided into quintiles. Percent differences were calculated to measure the variation between the highest and lowest quintiles. Results: Between 1992-1998 when the results of the phase III ACT trials were still unknown and utilization of ACT was low, areas with the highest treatment rates were 35 times more likely than areas with the lowest rates to administer ACT. After 2003 ACT use increased swiftly and geographic variation fell. In contrast, PORT utilization rates have declined and become more geographically dispersed since 1998. Receiving no adjuvant treatment was highest between 1999-2003, after the Lancet PORT meta-analysis and before the major ACT trials. Conclusions: NSCLC adjuvant treatment has been shifting from PORT to ACT. The positive results of the ACT trials and publication of treatment guidelines have increased usage and reduced geographic variation in ACT use. Geographic variation in PORT use however has increased over time, although overall usage has decreased. [Table: see text]
Cost-effective analysis of the use of EGFR inhibitors (E) for wild-type (WT) KRAS unresectable metastatic colorectal cancer (mCRC).
Authors: Riesco Martinez Maria C. , Berry Scott R. , Ko Yoo-Joung , Mittmann Nicole , Lien Kelly , Hassan Shazia , Giotis Angie , Chan Kelvin K.
Published: March 2020

6552

Background: Patients (pts) with unresectable WT KRAS mCRC benefit from fluoropyrimidines (FP), oxaliplatin (O), irinotecan (I), bevacizumab (Bev) and E. The most cost-effective strategy to combine them remains unclear. Methods: A Markov model was constructed for a hypothetical cohort of pts with mCRC to examine the costs and outcomes of 3 treatment strategies: (A): 1st line (1L) Bev+FP+O/I, 2nd line (2L) FP+I/O, 3rd line (3L) E, (B): 1L Bev+FP+O/I, 2L FP+I/O, 3L E+I, and (C): 1L E+FP+O/I, 2L Bev+FP+I/O, 3L best supportive care (BSC). Efficacy and probability data of the treatments were obtained from clinical trials identified through a systematic review of the literature. Resource utilization data were derived from a chart review of 65 consecutive pts treated at Odette Cancer Centre (OCC) since 2009 and from the literature. Utilities were obtained by surveying oncologists (n= 24) across Canada using EQ-5D. Costs were obtained from the Ontario Ministry of Health and Long/Term Care, Ontario Case Costing Initiative, OCC and the literature. The analysis was conducted from the Canadian public healthcare system perspective over a 5 year time horizon with a 5% discount in 2012 Canadian dollars (CAD$) for cost and outcome. Incremental cost-effectiveness analyses were conducted comparing costs and outcomes of the 3 strategies. One way and probabilistic sensitivity analyses (SA) were conducted (n=10,000). Results: All 3 strategies appeared to be of relatively similar efficacy clinically, but C is more expensive than A or B by >45% (see Table). The model is primarily driven by the acquisition cost of drugs. B is most cost-effective when the willingness-to-pay (WTP) threshold >$120,000/QALY. SA showed that C would be cost-effective only when the progression-free survival of E is better than Bev in 1L with hazard ratio <0.24 at WTP of $150,000/QALY. Conclusions: 1L use of E followed by 2L Bev in mCRC is not cost-effective at the current pricing of E relative to Bev. [Table: see text]
Validation of observed savings from an oncology clinical pathways program.
Authors: Scott Jeffrey A. , Milligan Scott , Wong Winston , Winn Daniel , Cooper Joseph , Schneider Neil , Parkes Sheamus , Feinberg Bruce A.
Published: March 2020

6553

Background: Oncology clinical pathways have been suggested as a way to decrease cancer treatment variation and costs. CareFirst BlueCross BlueShield (CFBCBS) partnered with Cardinal Health Specialty Solutions to launch the first cancer clinical pathway in the US in Aug 2008. Savings from that program were reported by Scott et al, ASCO 2010. The purpose of this study was to obtain third-party validation of the observed savings of this pathways program. Methods: We used CFBCBS claims data from Jan 2007 to Dec 2010 to identify patients (pts) with breast, colon, or lung cancer who were treated by physicians participating in the pathways program. We used Truven Health’s MarketScan database to retrospectively identify a control group treated by non-institutional physicians in a similar geographic region outside the CFBCBS network. We further balanced the groups using propensity score weighting to align primary diagnosis and demographics. The primary outcome was the sum of allowed cancer costs for 270 days after a patient’s first chemotherapy treatment. A secondary outcome was the probability of an inpatient (inpt) admission over the same time period. Many generalized linear models were fit for sensitivity testing. Boosted decision tree models were also used to fully capture all nonlinearities and interactions. Both types of models use the propensity score weights. All savings estimates were based on comparing trends between cohorts. Results: A total of 2424 CFBCBS pts were included in the analysis. The aligned control group consisted of 1490 pts. The treatment coefficient from the linear model for the primary outcome was -0.16 with a z-value of -3, which translates to a savings estimate of 15% for the program. The treatment coefficient from the logistic model for the secondary outcome of inpt admission reduction was -0.29 with a z-value of -2.5, which translated to a 7% reduction (from 50% to 43%) in hospital admissions. The boosted decision tree models confirmed results of a more moderate magnitude. Conclusions: We conclude that the CFBCBS pathways program saved upwards of 15% on cancer-related claims costs with a 7% reduction in the probability of an inpt admission. These findings are consistent with those previously presented and peer reviewed.
Disparities in first-course treatment of non-small cell lung cancer among different hospital types in the United States.
Authors: Singla Abhishek , Kallam Avyakta , Adusumalli Jayanth , Abu Hazeem Mahmoud , Silberstein Peter T.
Published: March 2020

6568

Background: Treatment of non-small cell lung cancer (NSCLC) involves surgery, chemotherapy and radiation therapy in various combinations depending upon stage. This study compares disparities in the 1st course treatment given to NSCLC patients amongst different hospital types. Methods: We analyzed National Cancer Data Base for differences in 1st course treatment received for NSCLC amongst 3 hospital categories- Community hospitals (facilities which diagnose and/or treat 100-649 cancer cases annually), Comprehensive Community Hospitals (facilities which diagnose and/or treat 650 or more) and Teaching/Research Hospitals (facilities associated with university medical schools or designated as Comprehensive Cancer Care Programs by National Cancer Institute). Chi square test was used for statistical analysis. Results: 975,229 patients with NSCLC received treatment in 1,399 U.S. hospitals between 2000 and 2010. 71%, 81% and 84% of patients presenting to Community, Comprehensive and Teaching/Research hospitals received 1st course treatment at those centers. Surgery was done in 64%, 77% and 81% of stage I; 52%, 62% and 71% of stage II and 16%, 20% and 27% of stage III patients treated by Community, Comprehensive and Teaching/Research hospitals respectively (p<0.001 for all comparisons) (Table). Also, chemotherapy was given as a part of 1st course treatment in 37%, 30% and 22% of stage II patients treated by these hospitals respectively (p<0.001 for all comparisons). Conclusions: Significant disparities exist in treatment of NSCLC amongst different hospital types. Patients treated at research/teaching hospitals hospital are more likely to receive surgery as 1st line compared to Community and Comprehensive hospital for stage I to III NSCLC. [Table: see text]
Feasibility of long-term patient reporting of toxicities from home via the internet during routine chemotherapy.
Authors: Judson Timothy J , Bennett Antonia V , Rogak Lauren J. , Sit Laura , Barz Allison , Kris Mark G. , Hudis Clifford , Scher Howard I. , Sabbatini Paul , Schrag Deborah , Basch Ethan M.
Published: March 2020

6575

Background: Patient-reported outcomes are increasingly used in routine outpatient cancer care to guide clinical decisions and enhance communication. Prior evidence suggests good patient compliance with reporting at scheduled clinic visits, but there is limited evidence about compliance with long-term longitudinal reporting between visits. Methods: Patients receiving chemotherapy for lung, gynecologic, genitourinary or breast cancer at a tertiary cancer center, with access to a home computer and prior email experience, were asked to self-report seven symptomatic toxicities via the web between visits. Email reminders were sent to participants weekly; patient-reported high-grade toxicities triggered email alerts to nurses; printed reports were provided to oncologists at visits. A priori threshold criteria were set to determine if this data collection approach merits further development, based on monthly compliance rates (75% or more participants reporting at least once per month on average) and weekly compliance rates (60% at least once per week). Results: Between September 2006 and November 2010, 286 patients were enrolled (64% female, 88% white, median age 58). Mean follow-up was 34 weeks (range 2-214). On average, monthly compliance was 83% and weekly compliance was 62%, without attrition until the month prior to death. Greater compliance was associated with older age and higher education, but not performance status. Compliance was greatest during the initial 12 weeks. Symptomatic illness and technical problems were rarely barriers to compliance. Conclusions: Monthly compliance with sustained home web reporting is high, even with only weekly email reminders, but weekly compliance is lower, warranting strategies to enhance compliance in routine care settings. Barriers are likely surmountable through further use of reminder systems and questionnaire access via portable media. Between-visit symptom reporting may lead to more patient-centered care, enhanced quality, and improved patient satisfaction. Clinical trial information: NCT00578006.
Impact of pathways on chemotherapy administration before death.
Authors: Neubauer Marcus A. , Garey Jody S. , Turnwald Brian , Harrell Robyn K. , Howell Josh , Hayes Jad , Bhowmik Debajyoti , Hoverman J. Russell , Brooks Barry Don , Beveridge Roy
Published: March 2020

6580

Background: Continuing IV chemotherapy (chemo) in patients (pts) with advanced cancer near death neither extends survival nor improves quality, but does increase costs. Pathways (PW) programs have focused on comparing treatment (tx) costs but have not evaluated the impact on chemo given near death. The primary goal is to evaluate IV chemo administered in the last 14 days of life for pts treated On-PW vs. Off-PW. Methods: Eligible pts: in US Oncology’s (USO) iKnowMed (iKM) EHR; diagnosis (dx) of breast, colon, NSCLC, SCLC or pancreas cancer; >/=3 visits to a USO clinic; assessed for Level I PW compliance in the last 12 mths of life; and a documented date of death. IV chemo received in the last year of life was assessed. Pts were defined On-PW if all tx was On-PW or if pts did not receive IV chemo 12 mths before death (best supportive care). Pts were defined Off-PW if any tx received was Off-PW. PW-status, age, sex, dx, and last line of therapy (LOT) received were assessed. Multivariate logistic regression analysis was used to assess if PW status predicted likelihood of chemo within 14-days of death. Results: From 7/1/09-6/30/12, 12,551 pts met inclusion criteria. PW status was independently associated with chemo 14 days before death. Pts treated Off-PW had a two-fold higher odds of receiving IV chemo within 14 days of death compared to pts treated On-PW (OR: 1.99; 95% CI: 1.77-2.26), see the Table. Findings were similar for each dx. Tx for pts On-PW vs Off-PW showed lower mean last LOT overall (1 vs. 2) and by dx. Conclusions: Pts On-PW were less likely to receive IV chemo within 14 days of death and had fewer LOT. This suggests adherence to Level I PWs is associated with improved quality metrics. [Table: see text]
Comparison of medical oncologists' approach to non-small cell lung cancer patients compared with breast cancer.
Authors: Patel Shivani C. , Hamann Heidi A , Patel Prapti Arvind , Schiller Joan H.
Published: March 2020

6601

Background: Despite recent advances in the management of non-small cell lung cancer (NSCLC), treatment disparities persist. Evidence suggests that primary care physicians (PCPs) have less awareness of the benefit of adjuvant chemotherapy for lung cancer compared to breast cancer. They may also be less inclined to refer advanced stage NSCLC patients for further treatment and closely manage pain. This study’s goal was to refine this focus on treatment comparisons with a survey of medical oncologists. Methods: Online case scenarios were provided to medical oncologists identified through participating state and institutional organizations. Medical oncologists were randomized to receive one of four scenarios on the basis of cancer type (lung v. breast) and smoking status (30 pack/year smoker v. lifetime non-smoker). Medical oncologists’ treatment approaches were compared. Results: Two hundred seventy-one medical oncologists participated in the survey. The majority were male (71%) with a mean of 16.5 practice years; 28% worked within an academic setting. There were no significant differences in adjuvant chemotherapy use for early stage patients (98.3% lung v. 98.4% breast) or second-line chemotherapy for progressive disease (93.7% lung v. 95.9% breast). Almost all medical oncologists reported that they would offer an available clinical trial to a patient who had progressive disease but a good performance status (PS), regardless of cancer type. However, more medical oncologists were “very likely” to start third line chemotherapy for advanced stage breast cancer (33.6%) compared to advanced stage NSCLC (18.4%; p=.01). Conclusions: Medical oncologists report consistent first- and second-line adjuvant treatment patterns for NSCLC compared to breast cancer. However, they are less likely to consider third-line chemotherapy for advanced stage NSCLC, suggesting subtle treatment disparities. This study was supported by an award by GlaxoSmithKline (GSK) and by a grant from the National Lung Cancer Partnership and its North Carolina affiliate.
The influence of diabetes severity on guideline-concordant treatment for stage I-III breast cancer in the National Program of Cancer Registries (NPCR) patterns of care for breast and prostate cancer study (POCBP).
Authors: Sabatino Susan A. , Thompson Trevor , Wu Xiao-cheng , Kimmick Gretchen Genevieve , Fleming Steven , Trentham-Dietz Amy , Cress Rosemary , Anderson Roger T.
Published: March 2020

6606

Background: Little is known about whether diabetes status or severity affects receipt of guideline-concordant breast cancer treatment, which may impact outcomes. Methods: We used data from a Centers for Disease Control and Prevention NPCR funded 7 state Patterns of Care study for 6912 stage I-III breast cancer cases diagnosed in 2004. We determined diabetes status and severity using the Adult Comorbidity Evaluation Index (ACE 27). We used National Comprehensive Cancer Network guidelines to define guideline concordant locoregional treatment (LR), adjuvant chemotherapy (CTX) and hormonal therapy. Using logistic regression models, we examined the association of diabetes severity with each treatment modality adjusting for age, race/ethnicity, area-level education and income, insurance, registry, BMI, comorbidity, tumor size, nodal status, histology, ER/PR status, HER2 status and grade. Results: Over 10% of women had diabetes (8.6% mild, 1.6% moderate/severe). Before adjustment, diabetes status was associated with lower guideline concordance for both LR treatment (82.1% vs. 86.3%, p=.01) and CTX (56.4% vs. 69.4%, p<.0001), and increasing diabetes severity was associated with decreasing guideline concordance for LR (86.3%, 82.7% and 79.3% for none, mild and moderate/severe respectively, p=.028) and CTX (69.4%, 57.5% and 50.4% respectively, p<.0001). After adjusting for all factors, diabetes severity was not significantly associated with LR treatment (OR 0.93 (95% CI 0.73 - 1.19) for mild and 0.74 (0.46 - 1.20) for moderate/severe vs. none, p=.43) or CTX (0.91 (0.73 - 1.13) for mild and 0.67 (0.41 - 1.10) for moderate/severe vs. none, p=.23). After adjusting first for sociodemographic factors, then adding comorbidity and BMI, and finally tumor characteristics, significance of diabetes severity was lost after adjusting for sociodemographic factors, largely due to age. Conclusions: Breast cancer patients with diabetes are less likely to receive guideline concordant LR treatment and CTX, with increasing severity associated with lower receipt. However differences appear largely due to age.
Chemotherapy-induced febrile neutropenia (FN) and FN prevention strategies in cancer care in the U.S. Veterans Health Administration (VHA).
Authors: Barron Richard L. , Wang Li , Baser Onur , Langeberg Wendy J. , Dale David C.
Published: March 2020

6608

Background: Chemo-induced FN can be a life-threatening adverse event requiring immediate hospitalization and is associated with increased infection-related mortality and healthcare costs. Because the VHA has a fully-integrated national claims database, we used this database to assess FN incidence, burden, and prevention strategies in VA cancer patients. Methods: VHA’s database includes de-identified inpatient, outpatient, pharmacy, and laboratory claims and EMR data. Patients ≥ 18 years old with lung, colorectal (CRC), or prostate cancer or non-Hodgkin lymphoma (NHL) who had initiated ≥ 1 course of myelosuppressive chemo from Jan 2006–Sept 2011 were included. Endpoints included chemo treatment patterns and FN incidence, burden (inpatient mortality, length of stay [LOS], and costs), and prophylaxis. FN was identified based on ICD-9-CM codes for neutropenia. Prophylaxis was defined as first use of any granulocyte colony-stimulating factor (G-CSF) or intravenous antibiotics within 5 days of chemo administration or oral antibiotics within 7 days before and 6 days after chemo administration in any cycle. Costs were estimated using hospital and laboratory claims containing an FN diagnosis. Results: 27,899 patients were eligible and were included in the analysis. Most were ≥ 65 years old (56%) and male (98%). See Table for selected endpoints. Conclusions: FN was a common event, and patients with FN had lengthy hospital stays, high inpatient mortality rates, and considerable costs. In the VHA, antibiotic prophylaxis was generally used more frequently than G-CSF prophylaxis. [Table: see text]
Prevalence and characteristics of prematurely terminated cancer clinical trials.
Authors: Stensland Kristian D , Latif Asma , Hendricks Ryan , Roper Nitin , McBride Russell , Hall Simon J , Oh William K. , Galsky Matt D.
Published: March 2020

6613

Background: Cancer clinical trials require a substantial investment of patient and financial resources. Trials that are terminated prematurely contribute little to the scientific knowledge base and divert resources from answering other critical questions. To our knowledge, the prevalence of prematurely terminated trials, and reasons for termination, has not been comprehensively assessed. Methods: The ClinicalTrials.gov database was queried to identify all phase II and phase III interventional trials for any neoplasm registered between 9/2005 and 11/2012. The disease type, enrollment status, phase, funding source, and number of study sites were collected for each trial. A ”prematurely terminated” trial was any trial with a status of “terminated,” “withdrawn,” or “suspended.” The reason for termination was collected for each prematurely terminated trial. Results: We identified 11,483 interventional cancer trials, of which 1,326 (11.5%) were terminated prematurely. The reasons for termination are shown in the Table. The proportion of cancelled trials was similar among the various disease types, but was slightly higher in lung cancer (14.4% vs. 11.2%, p = 0.001), and slightly lower in skin cancer (8.2% vs. 11.7%, p = 0.022). The most common reason for premature termination was poor accrual (33.1%) though no reason was provided for 23% of trials. Trials sponsored by industry were more likely to be canceled than those with NIH or “other” sponsorship (13.4% vs. 9.9%, p = 0.001). Single center trials were more likely to be canceled than trials with multiple sites (13.6% vs. 9.4%, p < 0.001). Conclusions: More than one in ten cancer clinical trials is terminated prematurely. Full reporting of the reasons for premature termination is necessary for further evaluation of the cancer clinical trial enterprise and identification of predictors of study early closure. [Table: see text]