bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II randomized study of avelumab plus entinostat versus avelumab plus placebo in patients (pts) with advanced epithelial ovarian cancer (EOC).
Authors: Cadoo Karen Anne , Meyers Michael L. , Burger Robert Allen , Armstrong Deborah Kay , Penson Richard T. , Gordon Michael S. , Fleming Gini F. , Moroney John William , Hamilton Erika Paige , Duska Linda R. , Wenham Robert Michael , Sankoh Serap , Brouwer Susan , Ordentlich Peter , Aghajanian Carol , Matulonis Ursula A. 
Published: May 2019

5511 Background: Preclinical evidence suggests that combining avelumab (A), a human anti-PD-L1 monoclonal antibody, and entinostat (E), a class I selective histone deacetylase (HDAC) inhibitor, may increase tumor immunogenicity and responsivity to checkpoint inhibition. This study evaluated whether A+E would lead to improved progression free survival (PFS) vs A in pts with advanced EOC. Methods: Pts with EOC which had progressed or recurred after 1st-line platinum-based chemotherapy and received 3- 6 lines of therapy were randomized 2:1 to receive A (10 mg/kg IV Q2W) plus E (5 mg PO QW) or A plus placebo (P). Treatment continued until disease progression (PD) or unacceptable toxicity. The primary endpoint was PFS (investigator-assessed, RECIST 1.1), stratifying on the presence/absence of bulky disease (tumor ≥ 50 mm) and platinum-refractory disease. The hypothesis was that the combination would reduce the hazard of PD or death by 43%, representing a 75% improvement in median PFS. 97 events (from 120 pts) provided 90% power with 1-sided significance level of 0.10. Secondary endpoints included ORR, duration and time to response, toxicity, clinical benefit rate, and OS. Results: 126 pts were enrolled, median age 63 yrs (range 43-82), median 4 prior lines, 83% serous histology. Median PFS was 1.64 and 1.51 mos for A+E and A+P, respectively (p = 0.31; HR 0.90, 95% CI: 0.58-1.39). No significant differences in ORR (6% vs 5%), or OS (NE vs 11.3 mos) were observed. 4 pts (3%) had clear cell EOC, with no responses observed. The incidence of related adverse events (AEs) was higher in the A+E arm compared to A+P (any grade: 93% vs 78%, Grade 3/4: 41% vs 10%), and the most frequent (≥20%) related AEs with A+E were fatigue (46%), nausea (31%), diarrhea (26%), anemia (26%), and chills (20%). Grade 3/4 related AEs occurring in ≥5% with A+E were fatigue (9%), and neutropenia (8%). 47% of pts in A+E arm required E dose holds/reductions. Discontinuations due to AEs were similar between arms (21% vs 17.5% for A+E and A+P, respectively), as was duration of study therapy (median 4 and 5 cycles started). Conclusions: In pts with heavily pretreated EOC, median PFS was not prolonged when E was added to A compared to A alone and the combination resulted in greater toxicity. Clinical trial information: NCT02915523.
Determination of eligibility criteria for salvage hysterectomy after definitive radiotherapy/concurrent chemoradiotherapy for residual cervical disease.
Authors: Takekuma Munetaka , Takahashi Fumiaki , Arimoto Takahide , Ishikawa Mitsuya , Ota Yukinobu , Kagabu Masahiro , Kasamatsu Takahiro , Kanao Hiroyuki , Kawamura Naoki , Kitagawa Ryo , Kudaka Wataru , Suzuki Shiro , Takehara Kazuhiro , Tanikawa Michihiro , Toita Takafumi , Hasumi Yoko , Fujiwara Satoe , Mizuno Mika , Kobayashi Hiroaki , Yaegashi Nobuo 
Published: May 2019

5524 Background: Patients with persistent cervical cancer after definitive radiotherapy/concurrent chemoradiotherapy (RT/CCRT) have a poor prognosis. Salvage hysterectomy (HT) is potentially curative, but eligibility criteria therefor have not been determined. Methods: Part 1) Retrospective review of patients with persistent cervical cancer treated with definitive RT/CCRT at 35 institutions of the Japanese Clinical Oncology Group (JCOG) from 2005–2014. Differences between a salvage HT group and a systemic chemotherapy (CT) group after definitive RT/CCRT for residual tumor were evaluated. Clinical variables influencing a salvage HT treatment decision were evaluated using logistic regression analysis. Part 2) Questionnaire-based survey conducted by JCOG gynecologic oncologists assessing treatment choice for patients with residual cervical disease after definitive RT/CCRT. Patients with residual cervical tumor before, during and after definitive RT/CCRT were surveyed for 86 conditions and appropriate candidates for salvage HT were evaluated using heat map analysis. Results: Part 1) We identified 298 patients who underwent salvage HT or systemic CT. Median overall survival was 3.8 and 0.9 year in the HT and CT groups, respectively (HR 0.4341, 95% CI 0.336-0.559, p < 0.01). FIGO stage and lymph node metastasis at initial treatment, performance status (PS) at diagnosis of residual cervical tumor and parametrial invasion of residual cervical tumor significantly influenced a salvage HT treatment decision. Part 2) Heat map analysis showed that surveyed variables segregated into 3 groups: i) in favor of salvage HT, ii) in favor of systemic CT, and iii) either. Conditions such as FIGO stage IB-IIB, PS of 0-1, residual tumor < 4 cm, no parametrial invasion and no residual lymph node metastasis were included in group i, in favor of salvage HT. Conclusions: Eligibility criteria could be determined based on the results of the current study, and a prospective clinical trial evaluating the survival benefit of salvage HT for residual cervical tumor after definitive RT/CCRT is being planned by JCOG.
Comparative benefit of interstitial needles in addition to intracavitary applicators in the treatment of locally advanced cervical cancer.
Authors: Lombe Dorothy Chilambe , Crook Juanita M. , Bachand Francois , Batchelar Deidre , Moore Jocelyn , Rose Tracey , Sherin Danielle 
Published: May 2019

5528 Background: Cervical cancer is the leading cause of cancer mortality of women in Low and Middle Income Countries (LMIC). Interstitial needles (IN) have improved outcomes but the resources required in comparison to intracavitary brachytherapy (IC) alone has impeded uptake in endemic regions. We conducted a retrospective review of the utilisation of IN in the management of locally advanced cervical cancer and simulated 2D planning by loading the applicators using standard Manchester loading (ML) to explore the magnitude of benefit that interstitial needles provide. Methods: 72 brachytherapy plans of 18 patients who had undergone treatment using tandem and ring and had interstitial brachytherapy between 04/2016 and 10/2018 were reviewed. ML plans prescribed to point A were generated to represent a 2D scenario but the known HR-CTV was taken into consideration and its dosimetric outcomes were compared to those of the 3D based plans. Results: The median tumour volume was 23 cm3. IN was used in 82 % of the insertions. The median number of IN was 2 (range 0 – 6) with median percentage of IN dwell time 6.6 % (range 0.68 – 38.5). V100 was excellent 98.2% for ML 97.3% for 3D IN and 98.7% for 3D non-IN plans. The median HRCTV D90 was 8.5 Gy/fraction (cumulative EQD210101.4 Gy) for ML plans and 8.0 Gy/fraction (cumulative EQD210 91.4 Gy) for 3D plans. The ML plans failed to meet the OAR goals except for the rectum, which was optimally distanced by the rectal paddle. The median bladder, sigmoid and small bowel doses were 24% above the recommended constraint in the individual plans and 15% cumulative EQD2. A statistically significant relationship was found between the number of needles utilised, tumour volume (p < 0.001) and coverage (p = 0.006) but not delivered dose (p < 0.068). Conclusions: 2D brachytherapy can provide adequate dose coverage for most tumours but IN provide a benefit in reducing the doses to OARs in a significant number of patients. This justifies investment in resources for uptake of interstitial needles to increase access to optimal treatment of cervical cancer for women in LMIC. This research was made possible an ASCO Conquer Cancer Foundation grant.
Comparison of definitive cervical cancer management with concurrent chemotherapy and radiation between two centers with variable resources and opportunities for improved treatment delivery.
Authors: Asamoah Francis Adumata , Scott Pearl Aba Anoa , Yuan Zhigang , Fernandez Daniel Celestino , Boateng Samuel Anoa , Montejo Michael E. , Agyeman Mervin Anoa , Aidoo Charles , Shahzad Mian M. , Chern Jing-Yi , Chon Hye Sook , Wenham Robert Michael , Vanderpuye Verna D. , Yarney Joel , Yamoah Kosj , Ahmed Kamran A. 
Published: May 2019

5534 Background: Cervical cancer remains a global health challenge particularly in low to middle income countries with under resourced healthcare systems. We present the experiences of two centers practicing in variable resource environments to determine predictors of improved radiochemotherapy outcomes. Methods: This retrospective review describes baseline demographic and clinicopathologic characteristics of cervical cancer patients treated with concurrent chemotherapy and radiation between 2014 and 2017 at the National Radiotherapy Oncology and Nuclear Medicine Center (NRONMC) in Korle Bu Teaching Hospital, Accra, Ghana and Moffitt Cancer Center, Tampa, Florida, USA. Results: Ghanaian patients presented at an older median age (56 vs. 49 years, p < 0.001), with predominantly stage IIIB disease (43% vs. 16%, p < 0.001) and squamous cell histology (89% vs. 79%, p < 0.001). Median treatment duration was longer for Ghanaian patients (58 vs. 52 days, p < 0.001). Ghanaian patients were less likely to receive concurrent chemotherapy (68% vs. 100%, p < 0.001) and interstitial brachytherapy implants (0 vs 19%, p < 0.001). No Ghanaian patients received a radiation boost to pelvic or paraortic lymph nodes (p < 0.001). Ghanaian patients had lower local control (64% vs. 93%, p < 0.001) and overall survival (82% vs. 95%, p = 0.02) at 24 months, respectively. For stages IB, IIA, IIB, IIIB, 24 month local control rates for NRONMC vs. Moffitt patients were (60% vs. 93%; p = 0.05), (89% vs. 100%; p = 0.35), (91% vs. 91%; p = 0.89), (53% vs. 91%; p = 0.02) and 24 month OS rates were (85% vs. 100%; p = 0.06), (100% vs. 100%; p = 0.48), (85% vs. 96%; p = 0.2), (73% vs. 91%; p = 0.24), respectively. Treatment duration > 55 days predicted poorer overall survival on multivariable analysis (MVA). Stage ≥III disease predicted poorer local control on MVA. Conclusions: Significant differences were noted in treatment and disease characteristics between the two centers. Feasible improvements for patients treated at NRONMC include removing financial barriers to chemotherapy access, improving radiotherapy delivery capacity to reduce treatment delays, and screening programs to reduce advanced disease presentation.
Recurrence and survival after robotic-assisted radical hysterectomy (RRH) for early-stage cervical cancer (CC): Experience may matter.
Authors: Fitzsimmons Christine K. , Stephens Amanda J. , Kennard Jessica A. , Manyam Madhavi , Pepe Julie W. , DeCoff Kayla M. , Ahmad Sarfraz , McKenzie Nathalie Dauphin , Kendrick James Erasmus , Holloway Robert W. 
Published: May 2019

5535 Background: The phase III LACC Trial found that minimally invasive surgery (MIS) / radical hysterectomy was inferior to open radical hysterectomy (ORH) with reduced disease-free survival (86% v 96.5%) and a higher disease-specific death rate (DSDR) (4.4% v 0.6%). We evaluated our experience with attention to the learning curve. Methods: Patients (pts) with early-stage CC (4/2007-12/2017) who underwent RRH with a uterine manipulator were evaluated in a contemporaneously maintained database. First 10 learning curve cases per surgeon (Group A) were compared to all subsequent cases (Group B). Inclusion criteria mirrored the LACC trial: > one-year follow-up, adenocarcinoma, adenosquamous, or squamous carcinoma, stage IA2 or IB1 using FIGO 2014 guidelines, and pathologic tumor size (TS) of 4 cm or less. Atypical histologies and lesions > 4 cm were excluded. Study parameters assessed included recurrence free survival (RFS), DSDR, and pattern of recurrence. Results: 144 RRH pts were identified and 90 met inclusion criteria with mean age of 45.6±14.3 years. Exclusions included stage 1A1 without LVSI (n = 13), atypical histology (n = 10), lost to follow-up (n = 13), and occult stage 1B2 (n = 18). 40 pts met Group A and 50 met Group B criteria. Median follow-up was 61±34.3 months (A = 71.5, B = 52.5). The 5-year RFS was 92% (95 CI ±4%) and the DSDR 5.5% (n = 5). There were 7 (7.8%) recurrences with median time to recurrence of 12±8.3 mos. Recurrence in Group A (n = 6, 15%) exceeded Group B (n = 1, 2%), p= 0.025. DSDR was 10% Group A v 2% B ( p= 0.184). The 4.5 yr RFS was 84.8% (95 CI ±7%) in Group A v 98% (95 CI ±3%) in Group B. There were no differences in risk factors for recurrence between A & B (TS > 2 cm, LN (+), adjuvant therapy (AT), and LVSI p> 0.05), except (+) vaginal margin status (A = 10% v B = 0%, p= 0.034). Three recurrences involved carcinomatosis, which may be insufflation related. All recurrent cases had TS > 2 cm and 5 received AT. Conclusions: In this study, recurrence of disease in early-stage CC clustered in the first 10 cases per surgeon and occurred in TS > 2 cm. This data suggests a possible learning curve effect and argues against a uterine manipulator cause. Carcinomatosis may be insufflation related, unique to MIS, and deserves further study.
Ofranergene obadenovec (VB-111) in platinum resistant ovarian cancer: with an immunotherapeutic effect.
Authors: Cohen Yael Chava , Berlin Suzanne T. , Birrer Michael J. , Campos Susana M. , Rachmilewitz Minei Tamar , Harats Dror , Penson Richard T. 
Published: May 2019

5542 Background: VB-111 is a targeted anti-cancer gene therapy with a dual mechanism: anti angiogenic/vascular disruption and induction of an anti-tumor directed immune response. We report final results of a phase I/II study of VB-111 in combination with paclitaxel in patients with platinum-resistant ovarian cancer. Methods: Study NCT01711970 was a prospective, open label, dose escalating study assessing combination treatment of VB-111 Q8W and weekly Paclitaxel. In the phase I part of the study patients were treated with escalating doses of intravenous VB-111 and Paclitaxel. In phase 2 patients were treated with therapeutic doses of VB-111 1x1013 Viral Particles and paclitaxel 80mg/m2. Assessments included safety, overall survival (OS), PFS, tumor response (CA-125 and RECIST) and histopathology. Results: 21 patients with recurrent platinum-resistant ovarian cancer were enrolled and treated in 2 US sites. Patients received a mean of 2.3 ±1.8 repeat doses of VB-111. 17/21 received the therapeutic dose. Median age was 65 (41-79) with a median of 3 (1-4) prior lines of therapy. Half of the subjects were Platinum refractory, and half were previously treated with antiangiogenics. No DLTs were observed. VB-111 was well tolerated and was associated with generally mild flu-like symptoms. In the therapeutic dose cohort, a 58% CA-125 GCIG response rate was seen in evaluable patients including durable responses, and responses in patients with platinum refractory disease and post anti-angiogenic failure . The median OS was 498 days in patients treated with Therapeutic Dose compared to 173 days in Sub-therapueutic dose (p = 0.028). Tumor Specimens taken after treatment demonstrated tumor infiltrated with cytotoxic CD8 T-cells and regions of apoptotic cancer cells. Conclusions: Treatment with VB-111 in combination with weekly Paclitaxel was safe and well tolerated. Favorable tumor responses and overall survival outcomes were associated with induction of an immunotherapeutic effect manifested as tumor infiltration with CD-8 T cells. Encouraging results are the basis for further exploration in the ongoing, placebo controlled, pivotal OVAL study. Clinical trial information: NCT01711970.
Recurrence of ovarian cancer in BRCAwt patients without maintenance therapy: Real-world evidence.
Authors: Louie-Gao Melinda , Aydin Ebru , Thaker Premal H. 
Published: May 2019

5547 Background: Development of platinum resistance is a major clinical challenge in ovarian cancer (OC) treatment. In the phase 3 ENGOT-OV16/NOVA trial of the poly(ADP-ribose) polymerase inhibitor (PARPi) niraparib, 55% of BRCA wild-type ( BRCAwt) patients (pts) receiving placebo developed platinum resistance after their last platinum-based therapy (ie, progressive disease within 6 months of their last chemotherapy [CT] dose). Niraparib, a PARPi approved for the maintenance treatment of adult pts with recurrent OC following platinum-based CT, significantly prolongs progression-free survival (PFS). This real-world data analysis investigated the risk of platinum eligibility loss for BRCAwt pts who did not receive maintenance therapy after platinum treatment. Methods: This retrospective study identified 5,535 pts with OC from January 2011–October 2018 using data from Flatiron, a longitudinal, demographically and geographically diverse database derived from records of > 265 cancer clinics and > 2 million US cancer pts. BRCAwt pts who had received ≥2 lines of platinum-based CT, had disease progression ≥6 months after their previous line of therapy, and had no maintenance therapy (PARPi, bevacizumab, or CT agents) after their current treatment were included. Kaplan-Meier analysis was used to estimate the probability of pts initiating next treatment or death, whichever occurred first, within 6 months. Results: Of 5,535 pts diagnosed with OC, 147 BRCAwt pts met the inclusion/exclusion criteria of this analysis (similar to ENGOT-OV16/NOVA placebo arm). An estimated 56% of pts received the next treatment or died within 6 months after their last platinum-based therapy. Median time to next therapy or death was 5.1 months (95% confidence interval, 3.1–7.2). Conclusions: Our real-world data analysis shows that 56% of BRCAwt pts who received platinum-based treatment without maintenance therapy had recurrent OC within 6 months, classifying them as platinum resistant. Use of maintenance treatment options, such as niraparib, has been shown to significantly prolong PFS after platinum-based CT and may be beneficial in extending the platinum-free interval, enabling pts to remain eligible for further platinum therapy.
Comparative performance of Breast Cancer Index (BCIN+) and CTS5 in hormone receptor-positive (HR+) lymph node-positive (N+) breast cancer patients with one to three positive nodes (N1).
Authors: Sgroi Dennis , Zhang Yi , Schnabel Catherine A. 
Published: May 2019

555 Background: Identification of N+ breast cancer patients with a limited risk of recurrence improves selection of those for which chemotherapy and/or extended endocrine therapy (EET) may be most appropriate to reduce overtreatment. BCIN+ integrates gene expression with tumor size and grade, and is highly prognostic for overall (0-10yr) and late (5-10yr) distant recurrence (DR) in N1 patients. Clinical Treatment Score post-5-years (CTS5) is a prognostic model based on clinicopathological factors (nodes, age, tumor size and grade) and significantly prognostic for late DR. The current analysis compares BCIN+ and CTS5 for risk of late DR in N1 patients. Methods: 349 women with HR+, N1 disease and recurrence-free for ≥5 years were included. BCIN+ results were determined blinded to clinical outcome. CTS5 was calculated as previously described (Dowsett et al, JCO 2018; 36:1941). Kaplan-Meier analysis and Cox proportional hazards regression for late DR (5-15y) were evaluated. Results: 64% of patients were > 50 years old, 34% with tumors > 2cm, 79% received adjuvant chemotherapy and 64% received up to 5 years of ET. BCIN+ stratified 23% of patients as low-risk with 1.3% risk for late DR vs those classified as high-risk with 16.1% [HR 12.4 (1.7-90.4), p = 0.0014]. CTS5 classified patients into 3 risk groups: 29% of patients as low-risk (4.2% DR), 37% as intermediate-risk (10.6% DR), and 34% as high-risk (22.1% DR) [HR intermediate vs. low: 2.3 (0.7-7.0), p = 0.16; high vs. low: 5.3 (1.8-15.5), p = 0.002]. In a subset of patients who completed 5 years of ET (N = 223), BCIN+ identified 22% of patients as low-risk with a late DR rate of 2.1%, while CTS5 identified 29% and 37% of patients as low- and intermediate-risk with late DR rates of 5.2% and 10.3%, respectively. Conclusions: BCIN+ classified N1 patients into binary risk groups and identified 20% patients with limited risk of late DR ( < 2%) that may be advised to forego EET and its attendant toxicities/side effects. In comparison, CTS5 classified patients into 3 risk groups, with low- and intermediate-risk of late DR of 4-5% and 10%, wherein the risk-benefit profile for extension of endocrine therapy is less clear.
Efficacy of maintenance olaparib for newly diagnosed, advanced ovarian cancer patients (pts) by BRCA1 or BRCA2 mutation in the phase III SOLO1 trial.
Authors: Friedlander Michael , Moore Kathleen N. , Colombo Nicoletta , Scambia Giovanni , Kim Byoung-Gie , Oaknin Ana , 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 , Lowe Elizabeth S. , Bloomfield Ralph , Disilvestro Paul 
Published: May 2019

5551 Background: In SOLO1 (NCT01844986), maintenance olaparib resulted in a significant improvement in progression-free survival (PFS) for newly diagnosed, BRCA1- and/or BRCA2-mutated, advanced ovarian cancer pts compared with placebo (HR 0.30, 95% CI 0.23–0.41; median not reached vs 13.8 months; Moore et al. N Engl J Med 2018). We investigated PFS in SOLO1 for the subgroups of pts with BRCA1 mutations ( BRCA1m) or BRCA2 mutations ( BRCA2m). Methods: All pts were in clinical complete or partial response to platinum-based chemotherapy and were randomized to maintenance olaparib (300 mg twice daily; tablets) or placebo. After 2 years, pts with no evidence of disease discontinued study treatment, but pts with evidence of disease could continue study treatment. PFS by BRCAm was a predefined analysis. BRCAm were identified by central germline (Myriad or BGI) or local testing; Foundation Medicine testing confirmed tumor BRCAm. Results: Median follow-up for PFS was ~41 months in the olaparib and placebo arms. Of 391 randomized pts, 282 had BRCA1m (72%), 106 had BRCA2m (27%) and three (1%) had both (Table). Two pts in the olaparib arm had somatic BRCAm (one BRCA1m, one BRCA2m); all others had germline BRCAm. At the primary data cut-off, 155 pts in the BRCA1-mutated group (55%), 43 in the BRCA2-mutated group (41%) and none in the BRCA1/2 -mutated group had disease progression. The percentage of BRCA1-mutated pts who received olaparib and were progression-free at 1, 2 and 3 years was 86%, 69% and 53% (vs 52%, 36% and 26% receiving placebo) and for BRCA2-mutated pts was 92%, 85% and 80% (vs 50%, 32% and 29%, respectively). Conclusions: Significant PFS benefit with olaparib versus placebo was demonstrated for all pts, regardless of whether they had BRCA1m or BRCA2m. Statistical tests were not used to compare BRCA1- and BRCA2-mutated pts, but those with BRCA2m appeared to receive greater benefit from maintenance olaparib than those with BRCA1m. Clinical trial information: NCT01844986. [Table: see text]