bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence and risk of central nervous system (CNS) metastases as a site of first recurrence in patients (pts) with HER2-positive (HER2+) breast cancer treated with adjuvant trastuzumab (T).
Authors: Olson Erin Macrae , Abdel-Rasoul Mahmoud , Wu Christina Sing-Ying , Maly Joseph , Pan Xueliang Jeff , Shapiro Charles L. 
Published: March 2020

609 Background: T is the mainstay of adjuvant therapy in pts with HER2+ breast cancer. CNS disease as the site of first relapse after exposure to adjuvant T has been reported, although the overall incidence and relative risk (RR) of this remains unclear. We performed an up-to-date meta-analysis to determine the risk of CNS metastases as the first site of recurrence in pts with HER2+ breast cancer who received adjuvant T. Methods: Pubmed databases were searched for articles from 1966 to 2011. Abstracts presented at the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium were also searched for relevant clinical trials. Eligible studies include randomized trials with adjuvant T administered for 1 year in pts with HER2+ breast cancer who reported CNS metastases as first site of disease recurrence. Statistical analyses were conducted to calculate the summary incidence, RR, and 95% CIs using fixed effects inverse variance models. Results: A total of 9,020 pts were included. The incidence of CNS metastases as first site of disease recurrence in HER2+ pts receiving adjuvant T was 2.56% (95% CI 2.07% to 3.01%) compared to 1.94% (95% CI: 1.54% to 2.38%) in HER2+ pts who did not receive adjuvant T. The RR of CNS as first site of relapse in T-treated pts was 1.35 (95% CI 1.02 to 1.78, p=0.038) compared with control arms without T therapy. In subgroup analyses, there was no significant difference in CNS incidence or risk between pts treated with concurrent versus sequential T (p=0.29), weekly versus every 3 week T (p=0.56), and no difference in the T groups between studies due to median follow up time in years (p=0.68). No evidence of publication bias was observed (Q=1.78; P=0.62; I2 = 0.0%). Conclusions: This is the largest report to date demonstrating that adjuvant T is associated with an increased risk of CNS metastases as a site of first recurrence in HER2+ breast cancer pts.
Association between financial relationships with commercial interests and research merit at the ASCO Annual Meeting (AM).
Authors: Moy Beverly , Bradbury Angela R. , Helft Paul R. , Sheikh-Salah Moktar , Egleston Brian , Sands Colleen B. , Storm Courtney D. , Peppercorn Jeffrey M. 
Published: March 2020

6095 Background: Financial relationships with commercial interests (COI) are common in cancer research. There are few data examining the correlation between COI and research merit. Meeting placement prominence (MP) and peer review score (PRS) are indicators of research merit. We examined the association between ASCO AM abstracts whose authors disclose COI and both MP and PRS. Methods: We reviewed abstracts presented at the ASCO AM in 2006 and 2008-2011. We evaluated associations between COI disclosed by any author and PRS and MP (order of prominence: plenary session (PS), clinical science symposium (CSS), oral presentation (OP), poster discussion session (PDS), vs. general poster session (GPS)). Chi-square tests, T-tests, and logistic regressions of COI were used to assess associations with MP, PRS, and year. Results: Of 12,446 total abstracts accepted for presentation, 78% of PS, 59% of CSS, 54% of OP, 52% of PDS, and 39% of GPS report at least one COI. Abstracts selected for PS, CSS, OP, and PDS had more COI compared to those selected for GPS (p < 0.05). Stock ownership COI were more frequently disclosed in PS (30%), CSS (30%), OP (22%), and PDS (22%) compared to GPS (16%) (p < 0.05). Employment COI were more frequently reported among abstracts presented at PS (39%), CSS (37%), OP (27%), and PDS (27%) compared to GPS (21%) (p < 0.05). Consultant COI were more likely to have higher MP than GPS placement (OR for PS=5.5; CSS=2.4; OP=2.2; PDS=1.9). Similarly, honoraria COI were more likely to have higher MP than GPS placement (OR for PS=3.9; CSS=1.8; OP=2.1; PDS=1.7). Better PRS was associated with COI (OR 0.17; p < 0.05). The relationship of better PRS with any COI strengthened over time from 2006, 2008-2011 (PRS times year interaction OR=0.65, p<0.001). Conclusions: ASCO abstracts whose authors report COI have higher merit as measured by MP and PRS. This suggests a dependence on industry relationships for access to important data that will lead to prominent cancer research. These relationships will require further investigation and ongoing management. To our knowledge, this is the first study examining the scientific merit of research with relation to COI.
Cost-effectiveness of adjuvant radiotherapy for older women with early hormone-receptor positive breast cancer.
Authors: Reeder-Hayes Katherine Elizabeth , Wheeler Stephanie B. , Biddle Andrea K 
Published: March 2020

6096 Background: Radiation therapy (XRT) following breast conserving surgery decreases local recurrence at the expense of additional morbidity and treatment costs. However, its utility in elderly women at low risk of recurrence has been questioned. This study assessed the cost-effectiveness of adding XRT to hormonal therapy (HT) in women over 70 with stage I, hormone-receptor positive (HR+) breast cancer after breast conserving surgery. Methods: A decision tree model was used to assess the costs and benefits of XRT + HT versus HT alone in 10,000 women age 70+ with stage I HR+ breast cancer. Using a societal perspective, we considered medical costs and quality of life effects of initial treatment, recurrences, and metastatic disease as well as long-term XRT-associated complications including breast fibrosis, chronic pneumonitis and cardiac disease. Probabilities of recurrence and death were modeled on recent clinical trial results, while toxicity probabilities were taken from literature review. The primary health outcome was incremental quality-adjusted life years (QALYs) gained. One-way and probabilistic sensitivity analyses (PSA) were performed to assess the sensitivity of model results and conclusions to various parameter estimates. Results: In the base-case scenario, the incremental cost-effectiveness ratio (ICER) for the addition of XRT was $923,017/QALY. The ICER was highly sensitive to variations in utility weights, particularly those reflecting patient preferences for initial treatment with or without XRT and those reflecting the decrement in quality of life resulting from breast fibrosis. In PSA, XRT was associated with lower quality-adjusted life expectancy at higher cost in 58% of simulations. Conclusions: In women over 70 with stage I HR+ breast cancer, the addition of XRT to HT is not cost-effective at a willingness-to-pay threshold of $100,000/QALY, and is associated with little or no improvement in quality-adjusted life expectancy. Providers should be aware that the cost-effectiveness of XRT in this population is strongly influenced by patient preferences surrounding recurrence and toxicity risks, and should weigh these factors when making shared decisions with patients.
Phase I trial of pegylated liposomal doxorubicin and lapatinib in the treatment of metastatic breast cancer (MBC): Final results.
Authors: Cianfrocca Mary E. , Kaklamani Virginia G. , Rosen Steven T. , Von Roenn Jamie H. , Rademaker Alfred , Smith Deborah A. , Rubin Stephen D. , Meservey Caitlin , Uthe Regina , Gradishar William John 
Published: March 2020

610 Background: Liposomal formulations including pegylated liposomal doxorubicin (PLD) were developed to improve the therapeutic index of anthracyclines (A). Lapatinib (L) is a selective, highly competitive inhibitor of ErbB1 and ErbB2 tyrosine kinases. Conventional doxorubicin plus trastuzumab was effective but with unacceptable cardiac toxicity. PLD plus L may be effective with less cardiac risk. Methods: This is a phase I, dose-escalation trial of PLD 20, 30, 45 and 60 mg/m2 IV every 4 weeks (maximum of 8 doses) and L, 1500 mg po daily until progression in patients (pts) with MBC. ErbB2 positivity was not required. Prior chemotherapy, endocrine therapy and trastuzumab were allowed. A subsequent amendment allowed prior L. Prior A use was limited to 240 mg/m2 of doxorubicin or 600 mg/m2 of epirubicin. Concomitant CYP3A4 inducers/ inhibitors were not allowed. A left ventricular ejection fraction (LVEF) of > 50% was required. The primary objective was to evaluate the safety (particularly cardiac), tolerability and feasibility of PLD and L. Results: 23 pts (PLD: 20 mg/m2 - 4 pts; 30 mg/m2 - 3 pts; 45 mg/m2 – 13 pts; 60 mg/m2- 3 pts) have been treated; total of 73 treatment cycles. Dose-limiting toxicity (DLT) was not reached. One pt had an LVEF drop to < 50% after 4 cycles accompanied by a pericardial effusion due to progressive disease. Treatment-related grade III/IV adverse events included: 4 pts with hand-foot-syndrome (HFS), 2 pts each with leukopenia, infection, and skin changes, 1 pt each with pain, fatigue, diarrhea, mucositis, hypoalbuminemia, anemia, cough, pleural effusion, and edema. Grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Response data in 21 evaluable pts: 4 PR, 5 SD, and 12 PD. Preliminary pharmacokinetic (PK) analyses (7 pts) indicate L has no effect on PLD (45 mg/m2) concentrations, but L concentrations were approximately 2-fold higher the day of PLD dosing. Conclusions: In 23 pts treated, PLD plus L was well tolerated with manageable toxicities and no treatment-related cardiac toxicity. DLT was not reached however grade 3 HFS occurred in 2 of 3 pts in the 60 mg/m2 cohort. Preliminary PK analyses demonstrate no effect of L on PLD, but an effect of PLD on L the day of PLD dosing.
Changes in adjuvant breast cancer chemotherapy regimen selection over time in the community.
Authors: Patt Debra A. , Espirito Janet L. , Turnwald Brian , Hoverman J. Russell , Neubauer Marcus A. , Cartwright Thomas H. , Busby Leslie T. , Brooks Barry Don , Sitarik Mark A. , Kolodziej Michael A. , Beveridge Roy A. ,   on behalf of the US Oncology Network Pathways Task Force
Published: March 2020

6109 Background: Adjuvant breast cancer (BC) chemotherapy (CT) treatment has evolved over time due to improved understanding of risk conveyed by pathology and patient (pt) characteristics, as well as emergence of new and mature data for survival and toxicity. We aimed to evaluate how CT regimen selection has changed in recent years in various subgroups. Methods: Using iKnowMed EHR data from The US Oncology Network, we retrospectively identified female pts diagnosed with stage I-III BC between 1/2007 and 12/2010 at practices with EHR data available at time of diagnosis. Pts with <5 office visits, those with a second primary or previous cancer diagnoses were excluded. Age, ER, HER2, nodal status, stage and year of diagnosis were captured. CT utilization was determined by the number of pts who received CT within 6 months of their diagnosis. Clinical trial pts were included. Regimens were categorized by the initial CT title and drugs assigned. Pts with metastatic regimens were excluded. CT regimens were analyzed by subgroups and trended over time. Results: During the time period, 26,095 stage I-III BC pts were identified. A CT regimen within 6 months of diagnosis was documented in 56% of pts. CT utilization was 83% in HER2+ pts, 85% in ER-/HER2- pts, and 45% in ER+/HER2- pts. CT utilization decreased overall with increasing pt age (71%, 64%, 51%, 33%, and 13% for pts in their 4th, 5th, 6th, 7th and ≥8th decade of life). In HER2+ pts, use of non-anthracycline containing regimens increased from 26 to 62%, and anthracyline-taxane combination regimens decreased from 33 to 15%. In HER2-/ER+ pts, the most used non-anthracycline regimen was docetaxel + cyclophosphamide (TC) at 41%. Anthracycline-taxane combinations were used more often in the HER2-/ER- group (32%). Conclusions: In the 4 year study period, this data suggests that ER and HER2 status may drive chemotherapy choice more than nodal status. Anthracycline containing regimens are being used less often possibly due to similar efficacy but less cardiac toxicity, particularly when combined with trastuzumab. These results suggest a change away from anthracyclines in specific subgroups with the controversy over the benefits of that change unsettled, and cost implications yet unquantitated.
Participation of teenagers and young adults (TYA) in cancer clinical trials (CCT): What can we learn from six years of accrual data in England?
Authors: Fern Lorna Anne , Lewandowski Jennifer Ann , Coxon Katy Marie , Fairbairn Elliann , Loucaides Eileen , Whelan Jeremy ,   National Cancer Research Institute's Teenage and Young Adults Clinical Studies Group
Published: March 2020

6115 Background: We reported underrepresentation of TYA in CTT in England, 2005-06. Since 2005 national healthcare policies and research initiatives aimed at increasing participation of TYA in CCT have been implemented. We aimed to determine if this has improved accrual rates (AR). Methods: We analyzed accrual by age during 2005-2010 to UK Cancer Research Network interventional trials recruiting newly diagnosed patients (pts) with leukaemia, lymphoma, bone/soft tissue sarcoma, central nervous system and germ cell tumours. AR were expressed as the ratio of pts entered onto trial compared to population incidence cases for 2005-08; for 2009-10, mean incidence of 2005-08 was used. Results: 2005-10 showed an AR increase of 10.3% for pts 10-14 yrs, 17.9% for pts 15-19 yrs but only 4.6% for pts 20-24 yrs (Table). In 2010 AR was 54.4% for pts 10-14 yrs, 43.3% for 15-19 yr olds and 20.6% for pts 20-24. Annual increases of AR were observed for pts 15-19 yrs, but in no other age groups, 0-59 yrs. We looked at AR for children and younger teenagers , 5-14 yrs, vs older TYA, 15-24 yrs. Overall, AR for 5-14 yr olds was greater, 53.7% vs 23.0% for pts 15-24 yrs; however, during 2005-10 AR increased by 9.7% for pts aged 15-24 compared to 7.8% for pts aged 5-14. Conclusions: AR for TYA has improved in between 2005-10. Most benefit is evident for older teenagers; AR for young adults remain disappointing. Changes relate to increased trial availability and access, centralisation of care for TYA, amendments to age eligibility criteria to reflect tumour biology and increased collaboration between adult and paediatric clinical research groups. Strategies to improve AR for young adults require further development. [Table: see text]
Prevalence and predictors of adherence to antiemesis prophylaxis in lung cancer: A population-based study.
Authors: Gomez Daniel Richard , Liao Kai-Ping Eric , Nguyen Hoang , Smith Benjamin D. , Elting Linda S. 
Published: March 2020

6124 Background: Nausea/vomiting is a significant toxicity in the treatment of lung cancer, but barriers exist to the delivery of prophylaxis. We studied compliance and predictors of prophylactic antiemetics with chemotherapy in this setting. Methods: We used a Texas state registry of clinical data linked with Medicare claims from 2001-2007. Our study population was incident lung cancers treated with platinum agents within 12 months of diagnosis. To define guideline-adherent care, we assessed compliance to the American Society of Clinical Oncology recommended prophylactic agents dexamethasone and a 5-HT3 antagonist. Adherence was scored as a binary variable and defined as administration within 24 hours of the first day of the first cycle of chemotherapy. We utilized a logistic regression model to evaluate the role of the following factors in predicting adherence: concurrent radiation therapy (RT), race (black vs. white), histology (small cell vs. non-small cell), rural location, Charlson Comorbidity Index (CCI), household income (by quartiles [Q]), education, and treatment year (binary). Results: Of 31,762 patients in the database, 5155 patients met the above criteria. The adherence rate to dexamethasone and 5-HT3 antagonists increased over time, from 51.5% in 2001 to 71.6% in 2007. Patients treated in the years 2005-2007 were 1.739 times more likely to be adherent to prophylaxis than were those from 2001-2004. Variables that predicted adherence (adjusted odds ratio [OR], 95% confidence interval [CI]) were: age (OR=1.013, CI [1.001, 1.026]), treatment year (OR=1.756, CI [1.548, 1.991]), race (black vs. white OR=0.684, CI [0.548,0.853]), median income (higher vs. lower OR=1.83 [Q2 vs. Q1]; OR=1.296 [Q3 vs. Q1]; OR=1.496 [Q4 vs. Q1]), CCI (1+ vs. 0, OR=0.613, CI [0.530,0.709]), and concurrent RT [yes vs. no OR=1.358, CI [1.197,1.541]). Conclusions: Compliance with guidelines for prophylactic antiemetics is suboptimal, but increasing over time. Several characteristics predict for improved adherence, including white race, median income, advanced age, and the receipt of concurrent RT. These findings highlight substantial economic disparities in supportive care of lung cancer in the state of Texas.
Geographic and socioeconomic determinants of participation by elderly patients in surgical oncology trials.
Authors: Stewart John H. , Russell Greg B. , Howard-McNatt Marissa Michelle , Petro Robin M. , Levine Edward Allen , Bell Ronny A. 
Published: March 2020

6127 Background: A recent report by our group demonstrated that <0.5% of elderly patients with breast, prostate and lung cancer participate in surgical oncology trials. However, little work to date has evaluated the roles of regional healthcare infrastructure and socioeconomic factors on clinical trial participation in this cohort. Methods: The NCI Cooperative Group Surgical Oncology Trial (CGSOT) database was queried for patients treated for breast, prostate and lung cancer cancer between 2000 and 2008 (n=13,541). Geographical Information Systems data were used to evaluate proximity to healthcare facilities while regional socioeconomic characteristics were obtained from the 2000 US Census and Area Resource file. Counts were used to create a proportion of respondents with the corresponding 95% confidence interval calculated using the central limit theorem. Independent t-tests were used to assess differences in outcome measures between the two age groups. Results: We found that 4136 participants in the NCI CGSOT database were 65 years of age or older. Interestingly, 92.7% of this cohort was white and 85.7% was female. Socioeconomic determinants of participation are shown in the table. Conclusions: The work presented herein suggests that elderly minority patients are less likely to participate in surgical oncology trials than their white counterparts. Furthermore, elderly participants tend to reside in less affluent areas. Future work will utilize interventions that improve the recruitment of elderly patients to these trials. [Table: see text]
Estrogen receptor (ER), Ki-67, p27Kip1, and histologic grade as predictors of pathologic complete response (pCR) in patients with HER2-positive breast cancer treated with neoadjuvant chemotherapy (NAC) using fluorouracil, epirubicin, and cyclophosphamide (FEC), taxanes, and trastuzumab.
Authors: Kurozumi Sasagu , Inoue Kenichi , Takei Hiroyuki , Matsumoto Hiroshi , Yoshida Takashi , Hayashi Yuji , Ninomiya Jun , Kubo Kazuyuki , Nagai Shigenori E , Oba Hanako , Kurosumi Masafumi , Tabei Toshio , Horiguchi Jun , Takeyoshi Izumi 
Published: March 2020

613 Background: NAC with taxanes and FEC concurrently with trastuzumab is a potent regimen in patients with HER2-positive breast cancer (BC). Several studies revealed high pCR rates in BC patients treated with this regimen; however, predictive factors and a prognostic effect of pCR have been still unclear. In this study, we analyzed several factors including p27Kip1 (cyclin-dependent kinase inhibitor acting as tumor suppressor) for correlation with pCR. We also evaluated differences in recurrence-free survival (RFS) or overall survival (OS) between patients with pCR and non-pCR, and with positive and negative nodes after NAC. Methods: Our study included 129 Japanese women with invasive, HER2-positive BC who received 12 cycles of paclitaxel or 4 cycles of docetaxel followed by 4 cycles of FEC-75 with concomitant trastuzumab for 24 weeks. We analyzed the correlation of pCR (no invasive lesions in the breast) and nodal status after NAC with RFS and OS, and analyzed the baseline expressions of ER, Ki-67, and p27Kip1, and histological grade for correlation with pCR. Positive or high expression was defined by nuclear labeling index: ER ≥10%, p27Kip1 ≥75%, Ki-67 ≥30%. Results: In 129 patients, pCR was found in 85 (66%). Patients with pCR after NAC had significantly better RFS than those without pCR (median follow-up: 41 months). Furthermore, patients with pathologically negative nodes after NAC had significantly better OS than those with pathologically positive nodes. Negative ER (79% vs. 40%), high Ki-67 (72% vs. 47%), low p27Kip1 (71% vs. 50%), and histological grade 3 (70% vs. 39%) were significant predictors of pCR. Conclusions: In patients with HER2-positive BC, this regimen was effective achieving the high pCR rate. pCR and pathologically negative nodes after NAC were predictive of RFS and OS, respectively. The expressions of ER, Ki-67, and p27Kip1, and histological grade at baseline were predictive of pCR. p27Kip1, a new predictor of pCR after NAC needs to be further analyzed.
Patient satisfaction with participation in phase II/III NCCTG clinical trials: Was it worth it? (N0392).
Authors: Chauhan Cynthia , Atherton Pamela J. , Satele Daniel , Dueck Amylou C. , Soori Gamini S. , Johnson David B. , Mandrekar Sumithra J. , Buckner Jan C. , Sloan Jeff A. 
Published: March 2020

6133 Background: Patient (pt) trial experience may give insight to quality of life (QOL) factors affecting accrual, retention and outcome. While pts are vital to clinical trial success, we know little about their post-trial opinions. This trial examined pt opinion of their trial and treatment decision making (TDM). Methods: Pts enrolled on designated North Central Cancer Treatment Group (NCCTG) phase II or III treatment trials completed the TDM Control Preferences Scale at baseline and the Was It Worth It (WIWI) satisfaction assessment at the ends of cycle 1 and active protocol treatment. The primary endpoint was the proportion of pts reporting worthwhile participation. Fisher Exact tests compared pt opinion across subgroups. Results: As of 01/15/2012, 264 pts were enrolled on 25 protocols and treated at 79 sites. 86% of pts were in phase II studies and 89% had stage IV disease. At the end of cycle 1, pts felt the trial was worthwhile (74%), would do it again (85%), and would recommend it to others (82%). 85% of pts reported undiminished QOL and only 7% rated the trial worse than expected. End of treatment responses were similar. Satisfaction rates varied by tumor site (p=0.04). 11% of pts having tumor response rated the trial as not worthwhile, and 66% of pts with progressive disease rated it worthwhile (see table). Pts with concordant preferred and actual TDM roles rated participation higher than pts with discordant TDM roles (see table). Conclusions: Most pts endorsed their clinical trial experience. Contrary to popular beliefs, treatment outcome did not have an overwhelming impact on pt satisfaction, and was just one of many factors such as TDM role discordance. Assessing pt satisfaction will inform future study design that can potentially improve pt accrual and retention. [Table: see text]