bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncotype DX testing in early-stage node-positive breast cancer and impact on chemotherapy use at a comprehensive cancer center.
Authors: Losk Katya , Freedman Rachel A. , Mittendorf Elizabeth A. , Tan-Wasielewski Zhenying , Trippa Lorenzo , King Tari A. 
Published: May 2019

549 Background: The 21-gene Oncotype DX Recurrence Score (RS) is widely used to guide adjuvant chemotherapy decisions in hormone receptor positive (HR+), HER2-negtive (HER2-), lymph node negative (LN-) breast cancer. It’s adoption in lymph node positive (LN+) disease remains controversial. In 2016, we implemented ‘reflex’ RS testing for patients ≤65 years with HR+/HER2- breast cancer including T1/T2 N1 (grade 1 or 2) tumors. Providers can also order Oncotype DX outside of reflex criteria. We sought to assess RS distribution and factors associated with chemotherapy use in HR+/HER2-/LN+ breast cancer patients at our center. Methods: Patients with non-metastatic HR+/HER2-/LN+ breast cancer who underwent primary surgery at our center were identified from our prospective database. We examined the distribution of low (RS < 18), intermediate (RS 18-30) and high (RS > 30) RS and identified characteristics for those who did not meet reflex criteria. A multinomial logistic regression model was performed to identify factors associated with chemotherapy receipt among all LN+ patients. Results: From 1/2016-3/2018, we identified 296 consecutive patients with HR+/HER2-/LN+ breast cancer. 200 (68%) patients had RS testing and 128 (64%) met reflex criteria. Reasons for not meeting RS reflex criteria included age > 65 (n = 35), grade III disease (n = 35) and N2/N3 tumors (n = 10). Among the 200 patients with RS, 122 (61%) had RS < 18, 67 (34%) had RS 18-30, and 11 (6%) had RS > 30. Only 68/200 (34%) patients with RS received chemotherapy as compared to 54/96 (56%) patients without RS (p = 0.0004). Compared to patients without RS testing, the odds of receiving chemotherapy were less with RS < 18 (OR = 0.46). The odds of receiving chemotherapy were greater with ≥3 positive LNs versus 1 positive LN (OR = 3.40). Conclusions: The majority of HR+/HER2-/LN+ patients undergoing upfront surgery at our center receive RS testing (200/296), with 122 (61%) resulting in low risk RS. Patients with low risk scores (RS < 18) were less likely to receive chemotherapy. While nodal involvement remains a common driver of chemotherapy use, our study demonstrates that RS testing provides clinically useful information in this population.
Results of a phase 2 trial of ribociclib and letrozole in patients with either relapsed estrogen receptor (ER)-positive ovarian cancers or relapsed ER-positive endometrial cancers.
Authors: Colon-Otero Gerardo , Weroha S. John , Zanfagnin Valentina , Foster Nathan R. , Asmus Erik , Wahner Hendrickson Andrea Elisabeth , Jatoi Aminah , Block Matthew Stephen , Langstraat Carrie L , Glaser Gretchen Elizabeth , Dinh Tri , Robertson Matthew , Camoriano John Kelly , Butler Kristina , Copland John A. 
Published: May 2019

5510 Background: Single agent aromatase inhibitor (AI) therapy is associated with limited clinical activity in ovarian cancer (OC) and endometrial cancers (EC). AI therapy was associated with a progression free survival (PFS) at 12 weeks of only 20% in relapsed OC (Bowman et al, 2002) and a median PFS of 1 month in relapsed EC (Rose et al, 2000). In Estrogen Receptor (ER) positive metastatic breast cancer, clinical studies had shown a significant prolongation of PFS with the addition of the cyclin kinase 4/6 inhibitor ribociclib to AI (Hortobagyi et al, 2016). Here, we report the results of a phase 2 clinical trial of the combination of ribociclib and letrozole in patients with relapsed ER positive OC or EC. Objectives: Primary endpoint was the proportion of patients with relapsed ER positive OC or EC alive and progression-free after 12 weeks of therapy (PFS12) with the combination of ribociclib given at a dose of 400 mg orally daily and letrozole 2.5 mg orally daily. A PFS of 45% was considered a favorable result based on the data referenced above from Bowman et al. Methods: Eligibility criteria included patients with relapsed ER positive OC or EC, with measurable disease, not previously treated with ribociclib or AIs. Xenografts were created from CT guided tumor biopsies at baseline to assess feasibility. Results: A total of 40 patients were enrolled (20 with OC and 20 with EC) ) with a median age of 61 years (range: 30-82) and 64.5 (range: 52-75) in the OC and EC groups respectively. Among the OC patients, 17 had high grade serous carcinomas and 3 had low grade serous carcinomas. 11 EC patients had endometrioid cancers (3 with grade 1 tumors) and 9 had high grade serous tumors. Ten out of 20 OC patients and 11/20 EC patients were alive and progression-free at 12 weeks (PFS12 of 50 and 55%, respectively). The most common grade 3 or higher adverse events (occurring in at least 5 pts) were leukopenia (18%), lymphopenia (18%), neutropenia (13%), and fatigue (13%). 34 tumor biopsies were suitable for injection into mice and 44% engrafted. ER expression persisted through multiple passages in mice. Two of three EC PDX models exhibited improved PFS with letrozole/ribociclib compared to letrozole alone. Conclusions: The combination of ribociclib and letrozole is associated with a promising 50% and 55% PFS12 in patients with ER positive relapsed OC or EC respectively. Creation of xenograft tumor models from CT guided biopsies of OC and EC tumors was feasible. Clinical trial information: NCT02657928.
Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-resistant ovarian cancer: Final findings from the FORWARD II study.
Authors: O'Malley David M. , Matulonis Ursula A. , Birrer Michael J. , Castro Cesar Martin , Vergote Ignace , Martin Lainie P. , Mantia-Smaldone Gina , Gilbert Lucy , González-Martín Antonio , Bratos Raquel , Esteves Brooke , Malek Karim S. , Moore Kathleen N. 
Published: May 2019

5520 Background: Mirvetuximab soravtansine is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of mirvetuximab soravtansine with bevacizumab (BEV) was evaluated in pts with FRα-positive, platinum-resistant ovarian cancer (recurrence within 6 months after last platinum). Methods: Pts received mirvetuximab soravtansine (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 66 pts received combination dosing at this level: 11 during escalation and 55 in expansion. The median age was 63 years, pts received a median of 3 prior lines of systemic therapy (range 1-8), and 62% had received prior therapy with BEV. The most common AEs were diarrhea (58%), nausea (50%), and blurred vision (48%), and were primarily low grade (≤ grade 2). Serious AEs were largely gastrointestinal in nature, with small intestinal obstruction the most frequent individual event (4 pts, 6%). Objective responses were seen in 27 pts for a confirmed overall response rate (ORR) of 41% (95% CI, 29, 54), median progression-free survival (mPFS) interval of 7.1 months (95% CI, 4.9, 9.5), and median duration of response (mDOR) of 8.6 months (95% CI, 4.9, 14.9). In a subset analysis of pts (n = 16) who were bevacizumab-naïve, had 1-2 prior therapies, and medium/high FRα levels (i.e., ≥ 50% of cells with at least moderate staining intensity) the ORR was 56% (95% CI, 30, 80), mPFS 9.9 months (95% CI, 4.1, 15.9), and mDOR 12 months (95% CI, 6.0, 14.9). Conclusions: The combination of mirvetuximab soravtansine with BEV exhibits favorable tolerability in pts with platinum-resistant ovarian cancer, characterized by a manageable side-effect profile. The encouraging efficacy compares favorably to reported outcomes for BEV and chemotherapy seen in similar patient populations. These data support continued exploration of the combination in ovarian cancer. Clinical trial information: NCT02606305.
Clinically significant discrepancy between clinical and pathologic stage of early-operable cervical cancer.
Authors: Gibbs Jennifer , Hastings Victoria , Malakhov Nikita , Economos Katherine , Kanis Margaux J 
Published: May 2019

5526 Background: The cornerstone of the management of cervical cancer (CC) traditionally relies on clinical examination assessment (CE) of tumor size (TS) and local extension of disease. Previous reports demonstrate poor accuracy of CE, with the most common discrepancy being failure to identify parametrial involvement (PI). The goal of this study is to determine the accuracy of CE in comparison to final pathology (FP) in early operable CC. Methods: This is a multi-center retrospective review of patients with early CC (FIGO stage IB1, IIA1). Data on age, race, histology, stage, CE findings, FP report and receipt of adjuvant radiation therapy (RT) were collected. CE findings included TS, PI and vaginal involvement (VI). CE of TS, PI, and VI were compared to FP. Subanalysis was also conducted based on TS ( < or ≥ 2cm) and location of tumor (exophytic vs endophytic). Analysis was performed using paired-T and Cohen’s Kappa tests. Results: Final analysis included 135 patients. Mean age was 52.6 years. The majority of patients had squamous cell carcinoma (72.6%). Overall, there was a significant difference between CE of TS compared to FP; mean error of 1.22 cm (p < 0.0001). In those with tumors ≥ 2cm the mean error was 1.28 cm (p < 0.0001). No significant discrepancy was observed in tumors < 2 cm (mean error: 1.10cm; p = 0.5). CE of TS of endophytic tumors was poor (mean error 1.68cm; p = 0.004) compared to exophytic tumors (mean error: 1.12 cm; p = 0.693). There was no significant difference in the identification of VI between CE and FP (3.7% vs 8.89%; p = 0.067). No patients with PI on CE were included in this analysis. However, 14.07% of patients were found to have PI on FP (p < 0.0001). There was no difference in the accuracy CE of TS between non-obese ( < 30 kg/m2) and obese patients (≥30 kg/m2), mean error 1.13 and 1.3, respectively (p = 0.061). As a results of FP, 55 patients (40.7%) received adjuvant RT and 38 patients (28.14%) were upstaged from IB1 to IB2. Of these 38 patients, 36 (94.7%) went on to receive adjuvant RT. Conclusions: CE of TS and PI is inaccurate, especially in tumors ≥ 2cm and endophytic tumors. This suggests imaging should be strongly encouraged, particularly in the setting of the updated FIGO 2018 staging system and recent debate over surgical approach.
Feasibility of visual inspection with acetic acid (VIA) screening for cervical cancer in Tanzania with emphasis on special populations.
Authors: Chinn Justine , Runge Ava , Dinicu Andreea , Chang Jenny , Ziogas Argyrios , Maher Justine , Naaseh Ariana , Lucas Alexa , Zezoff Danielle , White Kayla , Bera Kevin , Crawford Elizabeth , Cooper Emma , Bernstein Megan , Hari Anjali , Tewari Sujata , Rutaisire Eugen , Forthal Donald , Pearre Diana , Tewari Krishnansu Sujata 
Published: May 2019

5527 Background: Following the report that VIA screening reduced cervical cancer mortality by 31% in India (ASCO LBA2 2013; Shastri SS, et al JNCI 2014), the W.H.O. endorsed VIA guidelines for Africa, where the global disease burden is highest. In Tanzania, cervical cancer is a major source of morbidity and mortality, with nearly 10,000 new cases and 7,000 deaths annually. Due to lack of resources, therapies are limited and patient outcomes are further confounded by the relatively high prevalence of concurrent HIV infection. We report on the feasibility of VIA screening in Tanzania with emphasis on unique populations. Methods: Our two 5-day VIA screen-and-treat workshops in Buzuruga and Sangabuye Health Centres in Mwanza, Tanzania were approved by the University of California, Irvine IRB and local health authorities. Participants were recruited from surrounding communities and offered free cervical VIA screening, cryotherapy when indicated, and HIV rapid testing. Acetowhite lesions and/or abnormal vascular markings were VIA+. Chi-square and Fisher exact tests were performed with statistical significance assigned at 0.05. Results: During July 2018, 825 of 917 registered participants underwent VIA screening and 25.1% (n=207) were VIA+. 147 VIA+ non-pregnant women received same day cryotherapy and 15 (1.8%) with lesions suspicious for cancer were referred to Bugando Medical Center. In the subanalysis of 64 HIV+ patients (23 diagnosed at the workshops, 41 with prior diagnosis on ART), HIV infection was not associated with VIA positivity (p=0.497). Additionally, a non-significant trend of higher VIA+ screens among newly diagnosed untreated HIV patients (27.7%) vs patients with known HIV on ART (17.5%) was observed (p=0.556). Conclusions: VIA screening for cervical cancer, while feasible in Tanzania, will require follow-up and repetitive screening. Although cervical cancer is an AIDS-defining illness, lack of correlation between HIV infection and VIA-positivity may reflect the availability of W.H.O.-subsidized ART in sub-Saharan Africa to attenuate HPV-mediated neoplastic transformation, as previously reported by others. Further study of this phenomenon is warranted.
Safety and efficacy of nimotuzumab and concurrent intensity-modulated radiation therapy and chemotherapy for locally advanced cervical squamous cell cancer.
Authors: Qu Ang , Wang Junjie , Jiang Ping , Wang Panfeng , Zhang Muyi , Li Xu , Sun Haitao 
Published: May 2019

5532 Background: To evaluate the safety and efficacy of nimotuzumab plus concurrent intensity-modulated radiation therapy (IMRT) and chemotherapy for the treatment of locally advanced cervical squamous cell cancer (LACSCC). Methods: From December 2013 to March 2017, 31 patients with stage (FIGO 2009) IB2-IVA cervical squamous cell cancer were enrolled in this single-arm clinical trial at an academic medical center and received concurrent chemoradiotherapy plus nimotuzumab. All patients underwent at least 1 year of follow-up. The prescription radiation dose was 50.4 Gy/28 F on the pelvic field with or without extended-field radiation. An additional 30-36 Gy to Point A was delivered with high-dose-rate techniques. Cisplatin 40 mg/m2 and nimotuzumab 200 mg were infused intravenously once weekly during radiotherapy. The main and secondary outcome measures were toxicity evaluated using CTCAE 4.0., and the short-term outcome evaluated by RECIST 1.1. Results: The median follow-up duration was 29.7 months (13.3-61.2 months). All patients received external beam radiotherapy, brachytherapy, and nimotuzumab six times. Twenty-seven patients received six cycles of chemotherapy while four received only 4-5 cycles. There was no life-threatening toxicity. The incidence of acute grade 3 bone marrow depression was 51.6% (16/31) and grade 3 gastrointestinal tract reaction was 9.7% (3/31). The incidence of late toxicities was 22.6% (7/31), and these included vaginal-rectal fistula, intestinal obstruction, rectal hemorrhage, hematuria, and vaginal stenosis. Complete response was achieved in 30 cases (96.8%). The 1-year disease-free survival (DFS), local progression-free survival (LPFS), and overall survival (OS) rates were 87.1%, 90.3%, and 100%, respectively. The corresponding 3-year values were 74.8%, 90.3%, and 86.7%. Conclusions: Nimotuzumab plus concurrent IMRT and chemotherapy may represent a well-tolerated and effective treatment regimen in patients with LACSCC.
PD-L1 expression, DNA mismatch repair genes, and HPV types in cervical squamous cell carcinoma.
Authors: Haidary Tahmineh , Mendoza Rachelle Pacaanas , Zhou Yingyin , Lee Wen-Ching , Lee Yi-Chun , Gupta Raavi 
Published: May 2019

5533 Background: Previous studies observed low PD-L1 expression in cervical cancer, and that high PD-L1 expression is associated with deficient DNA mismatch repair genes and poor prognosis. No study has investigated the PD-L1 expression differences among HPV types in cervical cancer. We aim to determine PD-L1 expression in our patient population and its clinical significance. Methods: A total of 198 patients with SCC were identified and 60 had evaluable tumor specimens and clinical data. Immunohistochemistry on MMR genes and PD-L1 expression using tissue microarrays was performed. HPV analysis for 15 high-risk types was done by multiplex PCR and gel electrophoresis. Correlation between PD-L1 expression, MMR status, HPV types and other clinical parameters was analyzed using χ2 or Fisher's exact test. Cumulative 5-year survival was analyzed by Kaplan-Meier curves and log rank test. Results: Of the 60 patients, 90% were black, 55% between ages of 30-55 and 40% older than 55. 33 patients had poorly, 20 moderately, and 7 well-differentiated tumors. At 5-year follow up, 11 had recurrence, 14 patients died of disease and 7 lost to follow up. 93.3% of tumors had positive staining for PD-L1 with 56.7% showing high expression. Patients aged 30-55 showed a higher rate of PD-L1 expression. Majority had intact MMR (91.7%). High-risk HPV DNA was extracted in 41 specimens (68.3%), 11 of these were infected with ≥2 or more types, identifying 6 high-risk types not included in vaccine. Correlation analysis showed that there is significant correlation between age and PD-L1 expression on tumor cells (p = 0.047). No correlation between MMR status and PD-L1 expression. Mean disease free survival (DFS) was 43.7, 36.5, and 6.3 months for high, low and negative PD-L1 expression, respectively (p = 0.002). In patients with stage I-II disease, mean DFS was 52.2, 42.6 and 7.6 months for high, low and negative PD-L1 expression, respectively (p = 0.001). Similar direct relationship is observed with overall survival. Cases with mixed HPV infection are associated with late clinical stage at diagnosis (p = 0.037) and lower PD-L1 expression. Conclusions: Contrary to previous studies, our results showed remarkably high rate of PD-L1 expression in cervical SCC, which is associated with longer DFS and OS, especially in early stage tumors. Mixed HPV infection is associated with late clinical stage at diagnosis and lower PD-L1 expression.
Adverse events (AEs) with maintenance olaparib in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Phase III SOLO1 trial.
Authors: Colombo Nicoletta , Moore Kathleen N. , Scambia Giovanni , Oaknin Ana , Friedlander Michael , Lisyanskaya Alla Sergeevna , Floquet Anne , Leary Alexandra , Sonke Gabe S. , Gourley Charlie , Banerjee Susana N. , Oza Amit M. , González-Martín Antonio , Aghajanian Carol , Bradley William Hampton , Kim Jae-Weon , Lowe Elizabeth S. , Bloomfield Ralph , Disilvestro Paul 
Published: May 2019

5539 Background: In SOLO1 (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit vs placebo in newly diagnosed pts with advanced OC, a BRCAm and clinical complete or partial response to platinum therapy (HR 0.30; 95% CI 0.23–0.41) and was well tolerated (Moore et al. NEJM 2018). We analysed the most common AEs and hematologic AEs in SOLO1. Methods: Pts received olaparib tablets 300 mg twice daily or placebo until progression unless they had no evidence of disease at 2 years, in which case treatment stopped. AEs were graded using CTCAE v4.0. Results: Of 391 pts randomized, 390 (olaparib, 260; placebo, 130) were treated and included in the safety analysis. Median treatment duration was approximately 25 months for olaparib vs 14 for placebo. Median time to first onset of the most common AEs (nausea, vomiting, fatigue/asthenia, anemia) and neutropenia and thrombocytopenia was < 3 months; the first event lasted a median of < 2 months, apart from fatigue/asthenia, which lasted a median of < 4 months (Table). AEs were usually managed with supportive therapy and/or dose modification; few pts discontinued. Conclusions: AEs in newly diagnosed pts with advanced OC treated with olaparib usually occurred early and were manageable, with few discontinuations. Clinical trial information: NCT01844986. [Table: see text]
Circulating tumor DNA analysis to reveal genomic profiles for epithelial ovarian cancer.
Authors: Xiang Yang , Zhu Shan , Wang Weiran , Cao Dongyan , Wan Xi-Run , Yang Junjun , Yang Jiaxin , Yu Mei , Gong Yuhua , Guan Yanfang , Wang Jing , Li Peiling , Yue Ying , Zhang Guo-Nan , Wang Ping , Wang Yongjun , Xia Xuefeng , Yang Ling , Yi Xin 
Published: May 2019

5543 Background: Circulating tumor DNA (ctDNA) analysis in epithelial ovarian cancer (EOC) was previously reported, however with limited samples or limited genes. Here, we reported an analysis of ctDNA in EOC cohort using targeted sequencing with a 1021-gene panel. Methods: Patients with EOC were enrolled, and treatment-naïve tumor tissues and blood samples were collected. We utilized a 1021-gene NGS panel in matched tissue DNA and ctDNA to identify somatic mutations with white blood cell DNA as a germline control. Results: Mutations were identified in all of the 65 tissues and in 53 (81.5%) ctDNA. The median ctDNA mutation allelic frequency was 2.5%, ranging from 0.1% to 36.2%. A median of 66.7% (12.5%-100.0%) of tissue derived mutations were observed in ctDNA. Besides, there were 91 ctDNA private mutations, including TP53 gene mutations. The most frequently mutated genes were TP53 (55.4%), PIK3CA (13.8%) and ARID1A (12.3%) in ctDNA analysis, which were consistent with tissue analysis (60.0%, 26.2% and 20.0% of tissues with TP53, PIK3CA and ARID1A mutations, respectively). Mutations of TP53 (37/42) in high-grade serous ovarian carcinoma (HGSOC), PIK3CA (10/11) and ARID1A (8/11) in ovarian clear cell carcinoma, BRAF (4/5) in low-grade serous ovarian carcinoma and PIK3CA (3/5), ARID1A (2/5) and PTEN (2/5) in endometrioid carcinoma were observed as the most commonly genetic aberrations in ctDNA in different sub-types of EOC, which located in different signal pathways and suggested different pathogenesis. In total, 90.5% (38/42) of HGSOC were ctDNA positive, comparing with 65.2% (15/23) of other EOC subtypes (p = 0.012). In addition, 56.5% (13/23) of stage I~II EOC were ctDNA positive, comparing with 94.7% (36/38) of stage III (p = 0.002). No association between ctDNA positivity and other clinic characteristics was observed, including pathological differentiation, CA125, lesion density (solid vs. cystic-solid and cystic). Multivariable analysis suggested FIGO stage III (p = 0.008) as an independent predictor of ctDNA detection. Conclusions: In summary, genomic characterization of EOC may offer insights into tumorigenesis and identify potential therapeutic targets in this disease.