bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low baseline vitamin D levels correlate with adverse pathological features and clinical outcomes among patients with breast cancer.
Authors: Barakat Dina , Mohamed Rehab , Elnaggar Maha , Tarik Dalia , Eid Samir-Shehata M. 
Published: June 2022

552 Background: Serum vitamin D levels have been linked to breast cancer development; however, the impact on breast cancer features and outcomes remains unclear. The present study aimed at investigating the prognostic value of baseline vitamin D level among non-metastatic breast cancer patients. Methods: In this study; we prospectively assessed female patients presenting to our department with non-metastatic breast cancer during the period from October 2018 to December 2019 for their baseline serum vitamin D levels measured by ELISA test before starting systemic therapy, in addition to other clinicopathological factors. Low Vit-D was defined as Vit-D level less than 30 ng /l. Chi-square test (Fisher’s exact test) was used to examine the relation between qualitative variables. Survival analysis was done using Kaplan-Meier method and comparison between two survival curves was done using log-rank test. Multivariate analysis was done using Cox-regression hazard model for the significant factors affecting survival on univariate analysis. Results: We enrolled 221 patients with non-metastatic breast cancer as they matched our eligibility criteria. Median age at diagnosis was (50.7± 10.9). About two thirds of the patients (64.7%) were post menopause. Median vitamin D level was (23.1 ng/l) with a range of (4-62.46 ng/liter). Around half of the patients (56.5%) had vitamin D level lower than 30 ng/liter, with higher numbers of low vitamin D levels among HER2 positive and triple negative (TNBC) patients compared to hormonal receptor positive (HR+ve) patients (P=<0.001). There was a significant negative correlation between vitamin D levels and tumor size, lymph node positivity and stage at diagnosis (the lower the vitamin D level, the larger the tumor size, and the higher the number of positive lymph nodes and the stage; r= -0.414, r= -0.586, r= -0.674; respectively; p<0.001). On follow up, the number of local recurrences, bone metastases and liver metastases were significantly higher among the low vitamin D level group, however; there was no significant difference between the two groups in terms of development of brain and lung metastases. Disease free survival (DFS) and overall survival (OS) was significantly worse among the low vitamin D level group (p<0.001). Conclusions: Low serum vitamin D in breast cancer patients negatively correlates with tumor size, lymph node positivity and stage at diagnosis. It is linked to HER-2 positive and TNBC, and is significantly associated with worse DFS and OS.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) versus intravenous chemotherapy in unresectable peritoneal metastases secondary to platinum-resistant ovarian cancer: Interim analysis of Indian randomized control trial.
Authors: Somashekhar S.P. , Kumar Rohit , Rauthan Amit , Patil Poonam , Kapoor Priya , Rakshit Susmita , Rajgopal Ashwin K. 
Published: June 2022

5524 Background: PIPAC has emerged as a novel way to deliver intraperitoneal chemotherapy. PIPAC has shown improved response rate and quality of life in patients with inoperable peritoneal carcinomatosis. Methods: The trial is registered with Clinical Trials Registry – India (CTRI) REF/2018/08/021223. Interim analysis is presented here. Primary endpoint was to assess the objective response rate (With RECIST 1.1) between PIPAC and IV chemotherapy arm. Secondary endpoints were to assess quality of life (QLQ C-30) and morbidity (CTCAE 4.0 and Clavien dindo) between the two groups. PIPAC was done with dose of cisplatin 15mg /m2 and doxorubicin at 3mg/m2. The choice of chemotherapy was left at the discretion of treating physician. The response rate (With MRI & Ca-125) & quality of life assessment (QLQ C-30) of both the group was done periodically and recorded. Results: 40 patients underwent 105 PIPAC applications with nearly 25 (62.5%) had 3 cycles completed. 40 patients underwent IV chemotherapy same time with nearly 23 (57.5%) having received atleast 5 cycles. Mean age 57.3±8.05, PCI 24.45±6.39, with nearly 45.5% of patients had previous surgery and 72.5% of patients having received atleast 2 lines of prior chemotherapy and nearly 60 % having ascites. The objective response rate is 66.6% versus 22.5%, grade 3-4 events were 10.0% vs. 35.7 % in PIPAC and IV arm respectively. Histological regression was seen in 67.5% of patients with 3 cycles PIPAC. Functional, symptom and global health score at day 120 was significantly better with PIPAC arm when compared to IV arm. Conclusions: PIPAC is safe and feasible for patients with unresectable platinum resistant ovarian cancer. PIPAC showed better objective response rates and improved quality of life when compared to chemotherapy arm with acceptable morbidity. Clinical trial information: REF/2018/08/021223.
Efficacy and toxicity of carboplatin and gemcitabine dosed on day 1/day 8 versus day 1 alone for platinum-sensitive recurrent epithelial ovarian cancer.
Authors: Lampert Erika Joelle , Rose Peter Graham , Chambers Laura , Yao Meng , Michener Chad , Debernardo Robert 
Published: June 2022

5541 Background: Carboplatin, gemcitabine +/- bevacizumab is a preferred regimen for recurrent, platinum-sensitive ovarian cancer (PSOC). A phase III trial established that the regimen of carboplatin on Day 1 (D1) and gemcitabine on D1 and Day 8 (D8) was associated with acceptable toxicity and improved progression free survival (PFS) compared to carboplatin alone. Treatment with gemcitabine on D8 incurs more exposure to cytotoxic therapy and increased burden on patients and the healthcare system, especially during the COVID-19 pandemic. However, it is unknown whether D1/D8 gemcitabine imparts an improvement in efficacy compared to D1 alone. Our objective was to compare efficacy and toxicity of carboplatin and gemcitabine D1/D8 (CG-D1/8) with a modified D1 regimen (CG-D1). Methods: A retrospective single-institution cohort study was performed in women with recurrent PSOC treated with carboplatin, gemcitabine +/- bevacizumab from 2009-2020. Data was analyzed by intention to treat comparing women who received CG-D1/8 vs CG-D1. Data was also analyzed by 3 groups: CG-D1/8 vs CG-D1/8 but dropped D8 vs CG-D1. The primary endpoint was response rate (RR), defined as complete or partial response at 6 cycles or maximum cycles if <6. Secondary outcomes included PFS, overall survival (OS), toxicity, Neulasta use and dose reduction. Results: Of 200 patients, 26% completed CG-D1/D8, 21.5% started CG-D1/D8 but dropped D8, and 52.5% received CG-D1. There were no significant differences in age, race, or ECOG between cohorts. Among CG-D1/D8, 45.3% dropped D8 primarily due to neutropenia (51.2%) or thrombocytopenia (30.2%). The RR at 6 cycles was 68.7% for CG-D1/8 completed, 70.7% for CG-D1/8 dropped D8, and 69.3% for CG-D1 (p=0.97). The median PFS was 13.1, 12.1 and 12.4 months for CG-D1/8 completed, CG-D1/8 dropped D8, and CG-D1, respectively (p=0.29). Similarly, median OS was 28.2, 33.5 and 34.3 months for the above groups respectively (p=0.42). While there was no difference in concurrent bevacizumab use for CG-D1/8 and CG-D1 (34.7% vs 29.5%, p=0.43), among the CG-D1/8 patients, a significantly higher proportion of patients who dropped D8 received bevacizumab (51.2% vs 21.2%, p=0.006). Table 1 lists secondary outcomes. Conclusions: There was no significant difference in RR, PFS or OS among women with PSOC receiving CG-D1/8 vs CG-D1, regardless of whether D8 was dropped. CG-D1/8 was associated with significantly greater hematologic toxicity. These findings suggest a modified D1 regimen may be a suitable alternative to standard CG-D1/8 treatment and warrant prospective validation. [Table: see text]
Efficacy and safety of rucaparib maintenance treatment in patients from ARIEL3 with platinum-sensitive, recurrent ovarian carcinoma not associated with homologous recombination deficiency.
Authors: Coleman Robert L. , Oza Amit M. , Lorusso Domenica , Aghajanian Carol , Oaknin Ana , Dean Andrew , Colombo Nicoletta , Weberpals Johanne I , Clamp Andrew R. , Scambia Giovanni , Leary Alexandra , Holloway Robert W. , Amenedo Gancedo Margarita , Fong Peter C.C. , Goh Jeffrey C. , O'Malley David M. , Goble Sandra M. , Maloney Lara , Ledermann Jonathan A. 
Published: June 2022

5544 Background: In ARIEL3 (NCT01968213), rucaparib maintenance treatment led to significant improvement vs placebo for the primary endpoint of investigator-assessed progression-free survival (PFS) in patients (pts) with platinum-sensitive, recurrent ovarian carcinoma responsive to the last line of platinum therapy (Coleman et al. Lancet. 2017;390:1949–61). The largest benefit was observed in pts with carcinomas with a BRCA mutation or high loss of heterozygosity (LOH), a marker of homologous recombination deficiency (HRD). However, rucaparib also improved PFS in pts with carcinomas negative by HRD test (ie, BRCA wild-type with low LOH), a subset of pts for which there is no identified molecular mechanism conferring PARP inhibitor sensitivity. Among these pts (rucaparib, n = 107; placebo, n = 54), median PFS was 6.7 vs 5.4 months, respectively (HR, 0.58 [95% CI 0.40–0.85]; P= 0.0049), and 31.8% vs 4.3% were progression-free at 1 yr. In this post hoc exploratory analysis, we further evaluated the efficacy of rucaparib maintenance vs placebo in this subset of pts. Methods: Pts were randomized 2:1 to oral rucaparib (600 mg BID) or placebo. For this analysis, investigator-assessed PFS and safety were evaluated in pts with HRD-negative carcinoma, defined as BRCA wild-type with genomic LOH < 16% using Foundation Medicine’s T5 NGS assay. Results: Visit cutoff dates for efficacy and safety were Apr 15, 2017, and Dec 31, 2019. Across subgroups based on demographic or disease characteristics, the trend of rucaparib benefit vs placebo was consistently observed in pts with HRD-negative carcinoma (Table). The safety profile of rucaparib in the HRD-negative population was consistent with that of the overall safety population reported previously. Conclusions: Rucaparib maintenance reduced risk of progression in pts with ovarian carcinomas, including those not associated with HRD, regardless of clinical prognostic factors. [Table: see text]
Safety and efficacy of mitoxantrone hydrochloride liposome in patients with platinum-refractory or platinum-resistant ovarian cancer: A prospective, multicenter, open-label, single-arm, phase Ib clinical trial.
Authors: Huang Yu , Li Rong , Guiling Li , Luo Yanlin , Yang Zhijun , Lou Ge , Ouyang Weiwei , Xie Rong , Luo Wuxia , Chen Lixin , Zhou Qi 
Published: June 2022

5550 Background: Platinum-refractory or platinum-resistant ovarian cancer remains unmet medical need with an unfavorable prognosis. Its treatment options are limited and sequentially with multiple single-agent regimens or bevacizumab plus single-agent regimens are recommended. Mitoxantrone hydrochloride liposome (PLM60) is the first approved mitoxantrone nano-drug, which has shown favorable pharmacokinetic characteristics with long circulation and high cumulation in tumor tissue, thus has a promising anti-tumor activity. This trial aimed to explore the efficacy and safety of PLM60 in patients with platinum-refractory or platinum-resistant ovarian cancer. Methods: In this multi-center, open-label, single arm study, patients with histologically confirmed, epithelial ovarian, fallopian tube, or primary peritoneal carcinoma, either platinum-refractory or platinum-resistant, with at least one measurable lesion were recruited. PLM60 20 mg/m2 was administered on day 1 of each 21-day cycle for up to 8 cycles treatment or until disease progression or intolerable toxicities. The primary endpoint was safety, adverse events were graded according to CTCAE 5.0. Second endpoint included overall response rate (ORR), duration of response (DoR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS) as per RECIST 1.1. Results: 47 eligible patients with a median age of 54 years (range, 35-67) were treated in 7 institutions in China, including 15 platinum-refractory patients and 32 platinum-resistant patients. 32 (68.1%) of 47 patients received at least 3 prior lines of therapy. Treatment related adverse events (TRAEs) of any grade occurred in 45 (95.7%) of 47 patients, in which 31 (66.0%) were ≥ grade 3. The most common ≥ grade 3 TRAEs (incidence ≥10%) were leucopenia (51.1%), neutropenia (40.4%), anemia (19.1%), lymphocytopenia (17.0%) and thrombocytopenia (17.0%). At the cut-off data of October 31 2021, 39 patients were evaluable for response. ORR was 17.9% (7/39, 95% CI:7.5-33.5%, 7 PRs) and DCR was 56.4% (22/39, 95% CI:39.6-72.2%, 15 SDs). Among 21 platinum-resistant patients with ≥3 prior lines, the median DoR was 4.6 month, 2 responders had a DoR of > 6 months. The ORR and DCR of this cohort were 28.6% (6/21, 95% CI: 11.3-52.2%, 6 PRs) and 61.9% (13/21, 95% CI: 38.4-81.9%, 7 SDs), respectively. Median PFS was 3.6 month (95% CI 1.4-4.6), OS data was not mature. Objective response was not observed in platinum-refractory patients. Conclusions: PLM60 had an encouraging efficacy especially in platinum-resistant patients who had received at least 3 prior lines with tolerable safety profiles. Clinical trial information: NCT04718376.
Immune tumor microenvironnement (iTME) post-neoadjuvant chemotherapy, beyond PD-L1: Novel immune targets in ovarian cancer, data from the CHIVA trial, a GINECO/GINEGEPS study.
Authors: Blanc-Durand Felix , Yaniz-Galende Elisa , Genestie Catherine , Gauthier De Saint Basile Hortense , Chardin Laure , De Rauglaudre Gaetan , Raban Nadia , Chevalier Annick , Ferron Gwenael , Kaminsky Marie-Christine , Ray-Coquard Isabelle Laure , Hamizi Salima , Combe Pierre , Abadie Lacourtoisie Sophie , Joly Florence , Meunier Jérome , Floquet Anne , Alexandre Jérôme , Le Formal Audrey , Leary Alexandra 
Published: June 2022

5554 Background: Antibodies targeting PDL1 or PD1 have been disappointing so far in the treatment of ovarian cancer (OC). A greater understanding of the complex iTME and of the impact of chemotherapy on immune features could uncover promising immune targets. We previously reported that neoadjuvant chemotherapy (NACT) increased CD4+ and CD8+ immune cells (IC) and depleted FOXP3+ suppressive T-regs in OC iTME. Here we aimed to describe the expression of PDL1 as well as other co-regulatory molecules in OC and their changes under NACT. Methods: Tumor samples and clinical data were prospectively collected from patients (pts) in the randomized CHIVA trial of NACT +/- nintedanib. Samples were evaluable for immune profiling for 116-124 pts at diagnosis and 89-107 at surgery after 3 cycles of NACT. IC stained for CD4, CD8 were scored as number of IC+/mm². Expression of immune co-regulatory molecules PDL1, TIM3, LAG3 and IDO was scored as percentage of positive cells, and tumors were classified as PDL1/TIM3/IDO/LAG3 positive if > 1% of IC and/or tumor cells (TC) were positive. Highly sensitive pts, defined as objective response to NACT and prolonged median progression-free survival (mPFS > 24months), were compared to refractory pts (progressing during or within 3mo of platinum). Results: As expected, about one third (36%) of tumors were PDL1+ at diagnosis. In contrast, the prevalence of other co-regulatory molecules was higher with 52%, 54% and 93% of tumors being positive for IDO, LAG3 and TIM3, respectively. There was no significant change in PDL1 expression with NACT. However, in paired samples NACT significantly increased IDO and LAG3 expression (p < 0.05), such that 60% and 66% of tumors post-NACT were positive for IDO and LAG3, respectively. TIM3 expression remained high post-NACT with 92% of positive tumors. Highly sensitive tumors (vs refractory tumors) had significantly higher IC expression of TIM3 after NACT (24% vs 6%, p = 0.005), and were significantly more infiltrated by CD4+ (441 vs 228 cells/mm2, p = 0.04) and CD8+ (460 vs 225 cells/mm2, p = 0.045) T cells. Conclusions: Other immune targets beyond PDL1 are highly expressed in OC. In addition NACT appears to prime the iTME by increasing effector T cell infiltration and the expression of other relevant co-regulatory molecules (LAG3, TIM3 and IDO). Future studies could be performed by priming the iTME with NACT and testing novel immune therapies based on target expression in samples obtained at interval debulking surgery.
CeNtuRIOn: Rucaparib (R) with nivolumab (N) and ipilimumab (I) in patients (pts) with relapsed ovarian cancer (ROC)—Results of an initial safety cohort.
Authors: Hall Marcia , Allan Karen , Michael Agnieszka , Clamp Andrew R. , Glasspool Rosalind , Nicum Shibani , Lord Rosemary , Banerjee Susana N. , Roche Joshua , Stobo Jamie , Gourley Charlie ,   CeNtuRIoN Trial Group
Published: June 2022

5577 Background: There is an urgent need to improve outcomes for ROC pts; progression free (PFS)/overall survival (OS) are 4-9 months (mo), 12-20mo respectively. ̃50% ROC pts harbour homologous repair deficiencies (HRD), identified by BRCA mutations (m) & Loss of Heterozygosity (LoH). R, a PARP inhibitor (PARPi) has demonstrated efficacy when used as maintenance after chemotherapy (CT), and is superior to CT if used as treatment for ROC BRCAm pts. However repeating PARPi, even in highly selected BRCAm/HRD pts has limited benefit (1.5-2.5mo extra PFS). Single agent immunotherapy (PD-1/PD-L1/CTLA4 antibodies (Ab)) in ROC pts has been disappointing. Response rate to combined PD-1/CTLA4 Ab in ROC pts is 31.3%. In vitro evidence suggests that combinations of PD-1/CTLA4 Ab /PARPi may be more effective. CeNtuRIOn aims to explore the activity/toxicity of repeat PARPi (R) versus R+I (CTLA4 Ab) versus R+I+N (PD-1 Ab). Here we report safety data from the run-in cohort of 15 ROC pts treated with the triplet combination, RNI. Methods: Eligible pts had received ≥1 and <3 lines CT, were > 3 to <12 months from last platinum CT. Only 1 pt could experience a dose limiting toxicity (DLT) over initial 6 weeks of treatment. Pts received N 240mg q14 days, I 1mg/kg q42 days intravenously for up to 12mo and R orally, 600mg bd continuously. All bar 1 of 7 pts (recruited 06/19–12/19) received N+I to meet DLT evaluability, but 5 of remaining 6 received < 43% R during safety period. 6 further pts were recruited (08/20-06/21), with ≥60% starting dose R in first 6 weeks now required for evaluability. Review of toxicity/tolerability prompted reduction of R starting dose to 400mg bd and ipilimumab limited to 4 cycles for the last 4 pts. Results: Of all 15 recruits, median age was 64. Adverse events (AE)s are detailed in Table. 7 pts were evaluable for safety assessment: n = 4 started on 600mg bd and n = 3 on 400mg bd R. Median R dose intensity in these 7 was 82.5%. There was 1 DLT: G3 nephritis on day 18. 1 pt died of E. Coli sepsis related to colitis. Outcome data will be presented. Conclusions:R (400mg bd)+N+I (4 cycles only) will be taken forward to phase II. Pts will be randomised 1:1:2 to single agent R, R+I or RNI. Pts recruited to R alone are eligible for 2nd randomisation (1:1) to add I or N+I at progression. Clinical trial information: ISRCTN10490346. [Table: see text]
Trends in frontline PARP inhibitor maintenance in advanced epithelial ovarian cancer across the United States.
Authors: Huelsmann Erica , Deng Mengying , Handorf Elizabeth A. , Chu Christina , Jain Angela 
Published: June 2022

5581 Background: Advanced epithelial ovarian cancer (AEOC) is the fifth commonest cancer mortality among women in the United States. Despite 80% initial treatment response, most recur within two years and succumb from disease. Prolonging disease free interval with maintenance therapy is of interest. Options include Poly-(ADP) ribose polymerase inhibitors (PARPi’s) and Bevacizumab, an anti-angiogenesis agent; eligibility criteria are based on clinical trials. Here we examine national approach to front line maintenance therapy following treatment in AEOC with focus on PARPi use. Methods: Protocol for data collection was IRB approved and institutional IRB approved. A retrospective, observational cohort study using Flatiron Health electronic health record (EHR)-derived, de-identified database patients diagnosed with AEOC between March 2017-June 2020, following FDA approval of PARPi use in AEOC. Demographics were summarized using descriptive statistics by use of maintenance treatment, and associations were tested using ANOVA and Chi-squared tests. Trends in use and type of maintenance therapy were summarized by year. Time trends assessed by Cochran–Armitage tests. Results: 1196 patients met inclusion criteria: Age>18, Stage III-IV, 90-day gap rule, systemic therapy after diagnosis. Majority were >65, White, Stage III with ECOG 0 at diagnosis. Only 31.6% of patients received maintenance after frontline therapy. Single agent PARPi was most used (12.9%), and Olaparib was most used PARPi (57%). Use of maintenance therapy significantly differed by ECOG value at diagnosis (p=.005), region of practice (p=.003), use of surgery (p=<.001) and extent of debulking (p=.002). Maintenance therapy was used more often when ECOG low at diagnosis, optimal debulking achieved and with treatment in the Southern US. Maintenance therapy significantly increased by year (p=<0.001); highest in 2020 (46.9%). Type of maintenance therapy had a significantly different trend by year with PARPi becoming more common (p=<.001). Conclusions: Despite known high rates of response to maintenance PARPi and increased use over time, less than 50% of patients with AEOC receive this regimen. Reasons for low adoption of maintenance PARPi in this population with poor prognosis deserves further investigation. Olaparib, approved for single use in BRCA mutation carriers in the front-line maintenance setting was used more often than Niraparib, approved for all comers. [Table: see text]