bluuebunny/crossref_metadata_2025_split huggingface dataset:
Socioeconomic disparities in supportive therapy use and tolerance of aromatase inhibitors in patients with early-stage, hormone-positive breast cancer.
Authors: Kier Melanie Wain , Li Zhiqiang , Casasanta Nicole , Patel Rima , Agarwal Parul , Zimmerman Brittney Shulman , Yang Yunchen , Fink Marc Y , Zhou Xiang , Newman Scott , Chen Rong , Schadt Eric , Oh William K. , Tiersten Amy 
Published: June 2022

523 Background: Socioeconomic disparities impact breast cancer survival with significantly higher mortality among women of lower socioeconomic status. Little is known about how disparities affect patients with early-stage hormone receptor positive (HR+) breast cancer (BC) and patients’ tolerance and adherence to standard of care adjuvant aromatase inhibitor (AI) therapy. AI-related adverse effects are common and can cause therapy intolerance and early discontinuation. Supportive therapies have been shown to improve symptom tolerability when utilized by patients. This study assessed socioeconomic disparities in utilization of supportive therapies and adherence to initial AI therapy. Methods: We performed a retrospective chart review of all female patients at our academic institution with early-stage, HR+, BC who were initiated on adjuvant AI between 2011-2020. We collected information on side effects, duration of first AI and use of supportive therapies. We linked median family income with zip codes based on national census data and sorted them based on the Pew Research Center categorization. Primary endpoints were the rate of discontinuation of AI at 1-year and utilization of supportive therapies in relation to income, insurance coverage and primary language. The Fisher's exact test, Pearson's Chi-squared test, and Wald test methods were used to compare rates of discontinuation of front-line AI therapy and use of supportive therapies for each group. Results: We identified 1006 patients of whom 95% (n = 954) had AI related side effects yet only 31% (n = 311) received supportive therapies in the first year of AI treatment. The majority (59%) of patients were in the middle-income range ($52,200-$156,000), followed by upper (24%) and lower (17%) income. Upper-income was associated with higher use of supportive therapies (OR 1.46, p = 0.031) but was not associated with lower 1-year discontinuation rate. Medicare was the most common insurance coverage (45%), followed by Commercial (32%) and Medicaid (23%). English was the primary language for 86% of patients. Neither insurance coverage nor primary language was associated with either endpoint. In evaluating race, Black patients had the least use of supportive therapies (p < 0.001), yet this group had the lowest 1-year discontinuation rate (p = 0.005). Conclusions: Our results demonstrate that income and race were associated with use of crucial supportive therapies that are proven to help patients mitigate AI toxicities. The etiology of these disparities is likely multifactorial and requires further study to ensure equitable care and access for all patients.
Outcomes of patients with T1a,b N0 Her2-positive breast cancer treated with adjuvant trastuzumab in a prospective registry in Ontario, Canada.
Authors: Eisen Andrea , Gill Tripat , Habbous Steven , Beca Jaclyn M. , Arias Jessica , Chan Kelvin K. , Trudeau Maureen E. 
Published: June 2022

533 Background: Multiple randomized trials of chemo +/- tras in early stage, Her 2 positive BrCa demonstrated improvement in survival, but patients (pts) with T1a,b N0 disease were mostly excluded. Given the uncertainty of benefit in this group and the toxicities of chemo + tras, treatment in Ontario was funded for these patients conditional upon data collection for toxicity and survival endpoints. We report the outcomes for 483 patients enrolled in this Evidence Building Program (EBP). Methods: Between 2011 and 2018, 483 eligible pts with Her 2 pos disease and adequate cardiac function were treated with chemo + tras in the EBP. Cardiac toxicity, febrile neutropenia (FN), event-free (EFS), and overall survival (OS) were determined for this cohort from administrative datasets, and compared retrospectively to controls of similar stage selected from the Ontario Cancer Registry who did not receive tras and/or chemo. For the EBP cohort, clinicians also reported changes in left ventricular ejection fraction (LVEF). Results: Pt characteristics are shown in the Table. EBP patients had improved OS when compared to controls who received no chemo or tras. The 3-year OS in the EBP pts was 99.1%, versus 96.9% in the controls [adjusted HR 0.59 (95% CI 0.29-1.20)]. Patients receiving EBP tras had a significantly longer EFS than controls with or without chemo [adjusted HR 0.54 (0.36-0.83), p=0.005]. Use of chemo + tras in EBP pts was associated with an increased risk of clinical congestive heart disease (CHD) and febrile neutropenia (FN). About 3.5% of pts experienced CHD during treatment with chemo + tras. About 6% of pts had an absolute reduction of LVEF >10% or reached LVEF <50%. In an adjusted analysis, the risk of CHD was higher in older pts [HR 1.06 (1.03-1.08) per 1-yr increase in age, p<0.0001) and for pts who received anthracyclines [HR 5.00 (1.71-14.7). In a matched analysis, the crude frequency of FN during treatment was 20% in EBP pts vs. 3% among controls who did not receive chemo or tras (p<0.001). Conclusions: Analysis of the Ontario EBP for pts with, T1a,b N0 HER2 pos BrCa revealed that the prognosis is excellent and is improved with the use of chemo + tras. The safety profile was expected and tolerable, especially when non anthracycline chemo was used. These results led to a funding policy change where prospective data collection has been discontinued and chemo + tras is now routinely funded in this population. [Table: see text]
Efficacy and safety of initial five years of adjuvant endocrine therapy in postmenopausal hormone receptor-positive breast cancer: A systematic review and network meta-analysis.
Authors: Liao Hao , Zhong Jianxin , Pei Wendi , Bin Shao , Liu Xiao-ran , Rugo Hope S. , Li Huiping 
Published: June 2022

535 Background: Endocrine therapy has greatly improved the clinical outcomes of hormone receptor-positive breast cancer patients. However, there was an unmet need to identify the potentially best regimen of initial adjuvant endocrine therapy. Therefore, in this network meta-analysis, we synthesized the latest evidence to indirectly compare the efficacy and safety among different 5 years of regimens of initial adjuvant endocrine therapy. Methods: We conducted a systematic search of the PubMed, Web of Science, and EMBASE in January 2022. Randomized clinical trials assessing the efficacy and safety of initial 5 years of adjuvant endocrine therapy were included. The primary outcomes were disease-free survival (DFS) and overall survival (OS) and the secondary outcome was severe adverse effects (SAEs). A Bayesian network meta-analysis was carried out to indirectly compare all regimens and the SUCRA values were used to obtain rankings. Results: Eleven studies with 49,987 subjects were included. For DFS, exemestane (EXE) (hazard ratio [HR] 0.91, 95% confidence interval [95%CI] 0.87-0.96), anastrozole (ANA) (0.94, 0.90-0.97), letrozole (LET) (0.93, 0.89-0.97), tamoxifen (TAM) followed by EXE (0.91, 0.87-0.96), and TAM followed by ANA (0.92, 0.87-0.98) were more favorable than TAM, with TAM followed by EXE ranking as the first of SUCRA. For OS, only TAM followed by ANA showed significant superiority than TAM (HR 0.91, 95%CI 0.86-0.97) and ranked as the first of SUCRA. For SAEs, EXE (HR 1.72, 95%CI 1.04-2.98), ANA (1.58, 1.03-2.43), and LET (1.63, 1.02-2.57) showed greater associations with bone fracture than TAM. However, no significant difference in the incidences of cardiac events, thromboembolic events, and cerebrovascular events was found among all comparisons. Conclusions: The sequential use of aromatase inhibitors may be the optimal treatment mode for hormone receptor-positive postmenopausal early breast cancer patients. In addition, the three kinds of aromatase inhibitors achieved roughly equal efficacy, but caused different types of SAEs.
The real-world experience of adjuvant docetaxel and cyclophosphamide (TC) chemotherapy in HER-2 negative breast cancer.
Authors: Giffoni M. M. Mata Danilo , Chan Kelvin K. , Eisen Andrea , Pezo Rossanna C. , Menjak Ines B. , Trudeau Maureen E. 
Published: June 2022

538 Background: Adjuvant chemotherapy in breast cancer (BC) substantially improves overall survival (OS) and the risk of recurrence. The short and long-term side effects of anthracycline, and its modest benefits in the adjuvant setting, led to controversy about its role in comparison with TC. We aim to compare the OS of TC with anthracycline-based regimens in Ontario, the most populous province in Canada. Methods: We conducted a retrospective population-based cohort study using the Institute for Clinical Evaluative Sciences (ICES) database, involving females with stage I-III BC HER2-negative. Patients were treated with adjuvant chemotherapy between January 2009 to December 2017. The anthracycline regimens for comparison were as follows, FEC-D: Fluorouracil, Epirubicin, Cyclophosphamide, followed by Docetaxel; and ACT: Doxorubicin, Cyclophosphamide, followed by Docetaxel or Paclitaxel. Exclusion criteria included missing baseline characteristics, a prior history of malignancy or chemotherapy starting more than 120 days from breast surgery. The end of follow-up was March 31st, 2018. Adjusted analyses to compare OS by positive axillary lymph nodes (LN) and chemotherapy regimens were conducted with Cox proportional hazards models. Results: Of a total 10634 female patients with BC, 60% were ≥ 50 years-old, with 19.6% stage I, 61.1% stage II, and 19.3% stage III and 7130 (67%) women were classified as ER+ and 2379 (22.4%) as ER-. Among 5764 (54.2%) patients with positive LN, 4300 (40.4%) had LN 1-3 and 1464 (13.8%) had LN ≥ 4. There were 4945 (46.5%) high-grade cases. There were 2487 (23.5%) patients treated with TC, 2981 (28%) with ACT, and 5166 (48.5%) with FEC-D. With a median follow-up of 5.5 years, the OS comparison for the entire study population showed hazard ratio (HR) of TC vs ACT was 1.47 (95% CI 1.14 – 1.90), p = 0.0027 and TC vs FEC-D HR was 1.48 (95% CI 1.18 – 1.86), p = 0.0007. For ER+ patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.34 (95% CI 0.81 – 2.21), p = 0.26, and HR 4.29 (95% CI 2.09 – 8.79), p < 0.0001, respectively. For ER+ LN 0 patients, the OS HR of TC vs. ACT was 1.15 (95% CI 0.58 – 2.35), p = 0.67, and TC vs. FEC-D HR was 1.38 (95% CI 0.81 – 2.33), p = 0.23. For ER- patients treated with TC, the OS comparison of LN 1-3 and LN ≥ 4 vs. LN 0 showed HR 1.12 (95% CI 0.42 – 3.01), p = 0.82 and HR 4.41 (95% CI 1.33 – 14.59), p = 0.015, respectively. For ER- LN 0 patients, the OS HR for TC vs. ACT was 2.04 (95% CI 1.09 – 3.81), p = 0.025, and TC vs. FEC-D HR was 2.05 (95% CI 1.08 – 3.90), p = 0.028. Conclusions: Patients treated with adjuvant TC who had four or more axillary LN had significantly lower OS when compared to patients with LN 0. For women with ER- disease, TC demonstrated a significant unfavourable survival outcome when compared to anthracycline-based treatments.
Adherence to adjuvant endocrine therapy assessed by data from prescription renewals and medical records from tamoxifen in Swedish patients with cytochrome P450 2D6 (CYP2D6) genotyped early breast cancer.
Authors: Thoren Linda , Margolin Sara , Eliasson Erik , Bergh Jonas C. S. , Lindh Jonatan D. 
Published: June 2022

542 Background: Suboptimal adherence to adjuvant endocrine treatment (AET) is an important clinical concern. A correlation between CYP2D6 activity and tamoxifen discontinuation has been suggested. The main aim of this study was to investigate the consistency between prescription refill data and reports from medical records on adherence to AET in early breast cancer. We also studied if there was an association between menopausal status, CYP2D6 activity, estimated risk for recurrence and adherence to AET. Methods: 1235 pre-and postmenopausal Swedish breast cancer patients operated 2006 – 2014, genotyped for CYP2D6, who initiated adjuvant tamoxifen treatment, were included in the study. Information on AET was retrospectively collected from both medical records and the Swedish Prescribed Drug Registry. Consistency was defined as dispensed doses of AET divided by AET intake documented in medical records. Adherence was calculated for patients with at least 4.5 years of follow up and was defined as Medical Possession Rate (MPR) ≥ 80 %. Subgroup analyses were performed based on menopausal status, recurrence-risk and CYP2D6 activity. Results: In 84% of the patients the consistency of AET between the sources of information was within 80-125%. Consistency < 80% was most frequent in premenopausal/high risk patients and CYP2D6 Poor Metabolizers (PM). Among 899 patients with at least 4.5 years follow up, adherence to tamoxifen was 72% according to prescription refill data, compared to 77% as reported by medical records. When including aromatase inhibitors adherence increased to 82% and 88%. Adherence did not differ by menopausal status or risk for recurrence. CYP2D6 PM had poorer adherence (54%) to tamoxifen compared to patients with the highest CYP2D6 activity (83%). Conclusions: Consistency between medical records and dispensing data on adherence was better than anticipated. Adherence to AET was good, 82% when including switch to aromatase inhibitors. Surprisingly, CYP2D6 PMs had low adherence to tamoxifen, despite a reduced risk of side effects according to previous studies. Further work is needed to clarify the impact of CYP2D6 activity on adherence to tamoxifen.
Real-world effectiveness of first-line maintenance olaparib in women with BRCA-mutated advanced ovarian cancer: U.S. retrospective cohort study.
Authors: Eskander Ramez Nassef , Alam Naufil , Long Grainne H. , Ozgoren Ozan , Ambler Will , Volpe Stephanie , Moore Kathleen N. 
Published: June 2022

5518 Background: Following cytoreductive surgery and first-line (1L) platinum based chemotherapy, 70% of patients (pts) with newly diagnosed advanced ovarian cancer (AOC) experience relapse within 3 years. 1L maintenance treatment (tx) with olaparib monotherapy, a poly (ADP-ribose) polymerase inhibitor, extended progression free survival in pts with BRCA mutated (BRCAm) AOC in the SOLO-1 (NCT01844986) randomized controlled trial (RCT). We aimed to describe real world characteristics, tx patterns, and clinical outcomes of pts with newly diagnosed, BRCAm AOC. Methods: Data were collected from 457 pts via electronic case report forms in the US. Pt eligibility criteria were positive BRCAm test result between Jan-June 2019 (6 months post 1L olaparib FDA approval), newly diagnosed AOC (no maintenance tx prior to index), aged ≥18 years, no RCT enrollment, no active neoplasia, no prior tx for metastatic/stage IV cancer. Pt follow up was until July 2021. Kaplan-Meier (KM) estimation was used for time to event analysis using progression proxies: Time to subsequent therapy and discontinuation (or death for both) from initiation of 1L maintenance olaparib monotherapy. Results: Pt mean age (±SD) at index was 62 (±10) years, 64% of pts were white and 18% African American; further clinical characteristics are in the table. 95% of pts received ≥1 pharmacological tx. At 1L, 36% of pts (156/433) received maintenance tx after chemotherapy, with 64% of pts (277/433) receiving routine surveillance (no maintenance tx). Olaparib was the most common maintenance tx (67%, 105/156), with 67% of pts (70/105) prescribed olaparib monotherapy. At 24 months, the KM model estimated 91% of pts (95% confidence interval: 82, 96) would not progress to their subsequent therapy, with a median discontinuation of olaparib monotherapy of 25.0 (interquartile range [IQR]: 21.0, not estimable) months, over a median follow-up of 22.0 (IQR: 20.6, 24.0) months. Conclusions: This real world study complements SOLO-1 RCT data by demonstrating prolonged benefit of 1L olaparib in newly diagnosed pts with BRCAm AOC in terms of lower likelihood of progression (tx switch/death). To assess real world tx effectiveness globally, data collection across further eight countries is due to be completed in 2022. [Table: see text]
Basket study of oral progesterone antagonist onapristone extended release (ONA-XR) in progesterone receptor positive (PR+) recurrent granulosa cell (GCT), low-grade serous ovarian (LGSOC), or endometrioid endometrial cancer (EEC).
Authors: Grisham Rachel N. , Li Karen , Zhou Qin , Iasonos Alexia , Girshman Jeffrey , Shah Pooja , Jang Dasom , Kyi Chrisann , Cohen Seth M. , O'Cearbhaill Roisin Eilish , Friedman Claire Frances , Makker Vicky , Sabbatini Paul , Hensley Martee Leigh , Zamarin Dmitriy , Aghajanian Carol 
Published: June 2022

5521 Background: ONA-XR is a type I full progesterone antagonist that inhibits progesterone-mediated PR activation and stabilizes PR association with corepressors. GCT (98% of cases PR+), LGSOC (58% of cases PR+) and EEC (67% of cases PR+) are hormonally driven cancers that generally have poor responses to chemotherapy. Methods: This is an open-label, single-institution basket study of ONA-XR in patients with PR+ recurrent GCT (cohort 1), LGSOC (cohort 2), or EEC (cohort 3) (NCT03909152). Eligible patients required receipt of >1 prior line of chemotherapy, measurable disease by RECIST 1.1, and tumor tissue collected ≤3 years prior to enrollment with PR ≥ 1% by IHC. Patients received ONA-XR 50 mg PO BID until progression or intolerable toxicity. The study was designed as 3 parallel Simon 2-Stage studies. The primary objective was to evaluate efficacy, determined by RECIST 1.1, with at least 1/14 (cohort 1), 2/16 (cohort 2) or 4/19 (cohort 3) responses needed during stage 1 for advancement to stage 2. Secondary objectives included safety and tolerability, clinical benefit rate (CBR; stable disease lasting ≥ 16 weeks), and progression-free survival (PFS) as estimated by Kaplan Meier method. Results: The study enrolled patients to cohorts 1-3 from 5/2019 to 5/2020. Cohort 2 (LGSOC) enrolled 5 patients and cohort 3 (EEC) enrolled 1, both closed early due to slow accrual. Cohort 1 (GCT) enrolled 14 patients and completed Stage 1 accrual. There were no responses by RECIST 1.1 criteria observed in cohorts 1-3. In cohort 2 (LGSOC), 4/5 enrolled patients were evaluable, the median PFS was 4.4 months (1.8-NE) and CBR was 50% (6.8-93.2%). All 14 patients enrolled to cohort 1 (GCT) were evaluable with a median PFS of 3.5 months (1.6-8.8%), 6-month PFS rate of 30.1 % (8.4-56%), and 12-month PFS rate of 20.1% (3.5-46.4%). The CBR was 35.7% (12.8-64.9%). Two patients with GCT remain on active treatment for > 18 months. Grade 3 adverse events occurred in 5 patients: abdominal pain (2), small bowel obstruction (1), syncope (1), thromboembolism (1), urinary tract infection (1), and febrile neutropenia (1). Grade 3 laboratory toxicity occurred in 5 patients: anemia (2), neutropenia (1) and lymphopenia (2). Conclusions: ONA-XR was well tolerated and exhibited a 12-month PFS rate of 20.1% and a CBR of 35.7% in patients with GCT. No objective responses were observed. Cohorts 1-3 have closed to accrual, with 2 patients continuing active treatment for >18 months. Cohort 4, which combines ONA-XR with anastrozole, is currently enrolling patients with GCT. Clinical trial information: NCT03909152. [Table: see text]
Cytoreductive surgery plus HIPEC for advanced epithelial ovarian cancer: Analysis from a multicentric national Indian HIPEC registry of 1,470 patients—An ISPSM Collaborative study.
Authors: Somashekhar S.P. , Deo S.V.S. , Sekhon Rupinder , Rao Thammineedi Subramanyeshwar , Chaturvedi Harit , M S Ganesh , Joshi Rama , Kothari Kalpana , Gandhi Amit , Rajgopal Ashwin K. , Ray M D , Iyer R Rajagopalan , G N Hemanth , Kumar Rohit 
Published: June 2022

5525 Background: Improved long-term results can be achieved in advanced epithelial ovarian cancer (EOC) patients using optimal cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Methods: Indian society of peritoneal surface malignancy (ISPSM) is a registered body which maintains prospective data of 26 centers across India who perform CRS –HIPEC. From February 2017 until January 2022, 1470 patients with advanced EOC were treated with CRS-HIPEC. He general practice patterns and the oncological outcomes in terms of progression free survival (PFS) and overall survival (OS) & post-operative morbidity and mortality is reported. Results: Upfront (n = 156), interval (n = 645) and recurrent (n = 669) cytoreductions were performed based on the timeline at presentation. Mean age 54.5±10.74, PCI 13. 6±5.2, duration of surgery 10.6±1.h hrs. 36.4% had total peritonectomy, 12.7% had multivisceral resection, 41.8%had bowel resections and stoma rate was 7.4%. 60.3% had semiopen HIPEC, 83.1% used cisplatin for HIPEC and 83.1 % had HIPEC for 90 minutes. Overall G3-G5 morbidity was 25.4% with major ones being post-operative intra-abdominal collection (21.8%), electrolyte imbalance (16.4%), pulmonary (16.4%) followed by hematological (12.7%). Surgical morbidity was more in upfront cytoreduction group compared to interval group (20% versus 13.5%) and recurrent group (20% versus 15%), respectively. The 30 day mortality was 3.8%. With a median follow-up of 46 months, median PFS was 33 months in primary (upfront plus interval) group and 16 months in recurrent cytoreduction group. Median OS was not achieved in both primary and recurrent groups (4 year OS rates: 60 and 55%, respectively). Conclusions: This prospective database provides a collation and audit of the management of advanced epithelial ovarian cancer with CRS HIPEC in multiple centers registered under ISPSM. In advanced EOC patients, CRS plus HIPEC offers potential benefits in PFS and OS rates, with acceptable rates of morbidity and mortality and can be practiced even in resource constrained setting.