bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of testing for BRCA1/2 on outcomes in patients with ovarian cancer treated with PARPi in 1st line maintenance (1LM).
Authors: Gordan Lucio N. , Vasudevan Anupama , English Sandy , Roos Alison , Fares Marielle , Aton Lindsay , Wang Brandon , Blanc Simon 
Published: June 2023

e17576 Background: The treatment of ovarian cancer (OC) has expanded with the approval of PARPi in 1LM. Guidelines recommend that all women with OC get tested for BRCA1/2 and HRD status, given the therapeutic implication. Methods: This retrospective observational study used de-identified records from the Integra Connect PrecisionQ database enriched with information obtained by curation. Adult patients (>18 yrs) with OC who had initiated treatment between 01/01/2019 and 12/31/2021 were included. Categorical variables were reported as proportions and continuous variables as median (interquartile range, IQR), as appropriate. Results: In the 1,093 patients studied, the median age was 69 yrs and 75% had high grade carcinomas. Patients were predominantly White (74%); 9% were African American. 65% were ECOG 0-1 and 8% were ECOG 2. The first line (1L) treatment included platinum (Pl) chemotherapy alone in 60% (678) and Pl + bevacizumab (bev) in 37% (401), with 86% of patients being Pl-sensitive (929/1079). Most patients (84%, 782/929) received a BRCA test, of which 415 were tested for BRCA only and 367 were BRCA/HRD. The median turnaround time was 11 days (IQR=9) for BRCA tests and 15 days (IQR=35) for HRD tests. Of 929 patients who were Pl-sensitive, 503 (54%) received 1LM and 426 (46%) did not receive 1LM. Of 503 patients who received 1LM, 86% (435) had BRCA test results and 41% (208) had HRD results before maintenance initiation. In 48 patients who received 1LM, BRCA/HRD test results were not reported before initiation of maintenance. Patients who received Pl-only induction received bev (24), niraparib (94), olaparib (O) (78), rucaparib (5), O+bev (2), or nira+bev (6) in 1LM. Patients who had Pl+bev induction received bev (134), niraparib (28), O (29), and O+bev (57), or nira+bev (18) in 1LM. The median time to discontinuation (TTD) in all patient groups regardless of BRCA/HRD testing and results, was 24 mo. (13.8-NR) with O+bev and 22 mo. (17-NR) with O alone, compared to 7.8 mo. (6.9-10.1) with bev, and 8.2 mo. with niraparib (6.7-9.9). The probability of remaining on treatment at 3 mo. for O, niraparib, or O+bev was >90% compared to 80% with bev alone and remained high at 6 mo. (>80% for O or O+bev). The benefit was sustained for O and O+bev-treated groups, with an 18-mo. prob. of remaining on treatment of 57% (45-67) for O and 52% (36-65) for O+bev compared to 16% (10-24) for bev. Ongoing analyses will evaluate the TTD in patient subgroups by BRCA/HRD mutation status. Conclusions: Patients who had a test result and started a PARPi in 1LM had a longer TTD compared to bev-only treated groups, underscoring the importance of genetic testing for the initiation of 1LM and outcome improvement. [Table: see text]
Prognostic value of insulin-like growth factor receptor 1 (IGF1R) expression in high-grade serous ovarian cancer (HGSOC) treated with first line platinum derivative based chemotherapy.
Authors: Szymanowski Bartosz , Bieńkowski Michał , Pęksa Rafał , Cierniak Szczepan , Duchnowska Renata 
Published: June 2023

e17577 Background: Insulin-like growth factor receptor 1 (IGF1R) expression is frequently observed in ovarian cancer patients. Based on data from the literature, the IGF1(IGF2)/IGF1R pathway may be associated with resistance to platinum derivative based chemotherapy. Methods: The study group included 64 Caucasian women with serous high-grade ovarian cancer (HSOC) stage III-IV TNM/FIGO classification, treated 1st line platinum derivative based chemotherapy between 2004-2014. The analysis of clinical data was carried out based on data from medical records. IGF1R expression was assessed by immunohistochemistry using the monoclonal antibody Roche Rabbit Monoclonal (G11) in tissues from paraffin-embedded blocks. Progression free survival (PFS) was analyzed as the time from the start of chemotherapy to progression. Overall survival (OS) was defined as the time from diagnosis to the patient's death, regardless of cause, or to the last contact with the patient. In all analyses, the significance level was p = 0.05. Statistical analysis was performed using the 3.4.3 version of R statistical environment. Results: The median follow-up was 1023 days (range 157 to 3420 days). The median PFS was 14.0 (95%CI: 11.9-18.0) months. Median OS was not reached. The average patients age was 62 years (range 37-83). Platinum-sensitivity, partial platinum-sensitivity, platinum resistance and platinum-insensitivity were found in 23 (37.1%), 17 (27.4%), 21 (33.9%) and 1 (1.6%) patients, respectively. Any IGF1R expression was noted in 57 patients with the median H-score of 220 (range: 0-300; IQR: 100-207). Median PFS for IGF1R H-score 220 and IGF1R > 220 was 15.4 (95% CI: 13.1-23.3) and 10.8 (95% CI: 9.6-NA) months, respectively. In multivariate analysis PFS was associated with the extent of surgery: cytoreduction secondary vs. primary (WR = 1.94; p = 0.03), suboptimal vs. optimal (WR = 2.16; p = 0.01), body mass index (WR = 0.44; p = 0.05) and IGF1R expression ( > 220) (WR = 2.84; p = 0.04). Conclusions: High expression of IGF1R (H-score > 220) in stage III/IV HGSOC patients treated in 1st line platinum derivative-based chemotherapy is a negative prognostic factor.
Targeting regeneration capacity of stem cells to improve surgical wound healing outcomes in ovarian cancer patients.
Authors: Kelly Rebeca , Buchbinder Michelle , Aviles Diego , Hunter Krystal , Ostrovsky Olga 
Published: June 2023

e17578 Background: Despite advancements in care and treatment, ovarian cancer continues to be a challenging and deadly disease. Currently, standard treatment comprises a combination of cytoreductive surgery, often followed by platinum-based chemotherapy, known to negatively affect wound healing recovery. Therefore, achieving optimal post-surgical wound healing is critical in preventing delays in treatment, which can greatly impact patient outcomes and overall survival. Adipose-derived stem cells (ASC) have been shown to be crucial in regeneration of tissue and wound closure, as well as in regulating inflammatory differentiation and proliferation processes. Thus, improving the regeneration capacity of ASCs in wounds may speed post-surgical recovery and subsequent treatments. While a number of compounds have been shown to potentiate the regeneration ability of ASCs, we hypothesize that naturally derived epigenetic compounds with anti-cancer properties (I3C and EGCG), as well as anti-inflammatory compounds (non-psychoactive cannabidiol, CBD), may have a role in increasing regeneration capacity of stem cells. Therefore, ASCs were primed with these compounds and expression of major inflammatory, anti-inflammatory, proliferation and regeneration markers was evaluated. Methods: ASCs were primed with either I3C 50uM, EGCG 10 uM, or CBD 100nM. Conditioned medium from these treatments was collected and underwent a protein array assay for detection of levels of 40 human inflammatory markers and cytokines according to the manufacturer instructions. A one-way ANOVA test and Tukey post-hoc testing analyzed intensities for each marker between the control group and each of the primed groups. Results: Our results indicate that ASCs primed with our epigenetic treatments significantly decrease expression of a multitude of inflammatory markers and cytokines. I3C primed ASCs showed significantly decreased expression of the following factors: I-309, IL-11, IL-12 p40, IL-12p70, IL-1α, IL-6sR, M-CSF, MIG, MIP-1α, MIP-1β, MIP-1δ, IL-6, MCP-1, TIMP-2. EGCG primed ASCs significantly decreased expression of IL-12p70, IL-13, IL-6sR, MIP-1α, MIP-1δ, RANTES, IL-6, IL-8, MCP-1, TIMP-2. CBD primed ASCs significantly decreased expression of IL-6. A p< .05 was used. Conclusions: Priming ASCs with EGCG, I3C and CBD significantly down-regulate expression of a number of pro-inflammatory markers known to delay and interfere with the kinetics of wound healing processes, including wound inflammation, closure and scar formation. Therefore, these results suggest that naturally derived epigenetic compounds and CBD successfully potentiated ASCs’ ability to attenuate inflammation and wound healing processes. Consequently, our findings can lead to new diet and surgical ASC protocols which could optimize cancer post-operative wound healing closure time while decreasing inflammation.
Clinical assessment of HRD scoring in relation to PARPi response in terms of statistical guidance on reporting results for CDx tests evaluation.
Authors: Bisgin Atil , Boga Ibrahim , Eskut Kaan Ihsan , Rencuzogullari Cagla , Sonmezler Ozge , Kose Fatih , Besen Ali Ayberk , Olmez Omer Fatih , Disel Umut , Kocer Nazım Emrah , Bolat Filiz , Jinga Dan-Corneliu , Lazar Ioana , Pathak Surajit 
Published: June 2023

e17597 Background: Homologous recombination deficiency (HRD) is a tumor characteristic that can be assessed via different biomarkers such as individual mutations in BRCA1 and BRCA2 genes, and/or other HRR genes and genomic instability. We assessed a combined HRD score in three measures; BRCAs mutations, HRR mutation (HRRm) status, and genomic instability scoring via a specific bioinformatic algorithm of the testing panel to establish clinical validation. Methods: We tested 157 ovarian cancer patients’ FFPE samples to define HRD score, BRCA1/2 mutation and other HRRm status, to camper the responses to PARP inhibitors. For the HRD scoring, all the samples that were previously tested with alternative HRD tests and the cases had an indication of PARPi also tested via HRDInfo (CE-IVD) Panel for clinical diagnostics in this study. The PPA, NPA and OPA have been measured according to the FDA regulations of overall agreement for a follow-on CDx to show clinical evidence. Results: Depending on the three levels of testing strategy, BRCA1-2 mutation status in relation to the clinical response for PARPi has the lowest positive percent agreement (PPA) with 63.41% while HRD score has the highest with 97.62% that is higher than the any alternative HRD tests. All the PPA, NPA and OPA measures showed in the Figure for BRCA1-2 status and Genomic Instability stand alone and all BRCA1-2 plus other HRR genes plus Genomic Instability Status (GIS) to define HRD scoring. Conclusions: Even though the testing rate of HRD tests are still low all around the world and limited to specific cancers, there is an increasing requirement for different types of cancers. However, most alternative HRD tests have high overall concordance but fail to reach FDA CDx test requirements. Thus, this study showing the clinical evidence in the treatment of PARPi response data together with high PPA, NPA and OPA measures of HRDInfo panel and its bioinformatics algorithm. [Table: see text]
Real-world outcomes of first-line maintenance with niraparib or bevacizumab in advanced ovarian cancer.
Authors: Vasudevan Anupama , English Sandy , Gart Mike , Oladipo Taofikat , Hartman John , Iadeluca Laura L. , Kudrik Fred J. 
Published: June 2023

e17598 Background: Niraparib and bevacizumab are the only FDA-approved first-line maintenance (1LM) therapies for advanced ovarian cancer (AOC) without a biomarker requirement. However, little information exists regarding the effectiveness of these treatments in the real world. Methods: We identified 89 AOC patients from the US-based deidentified Integra PrecisionQ database who received 1LM bevacizumab (n=31) or niraparib (n=58) following induction chemotherapy (CT) ± bevacizumab initiated between July 1, 2019, and March 31, 2021, and followed them until the data cut-off of March 31, 2022. Using the start of maintenance therapy as the index date, we examined patient characteristics, time to next treatment or death (TTNT; often used as a real-world proxy for progression-free survival), and overall survival (OS) for these treatment groups. Results: For patients who received 1LM bevacizumab, the median age was 69 years, 65% had Stage III cancer at index date, 84% had Eastern Cooperative Oncology Group (ECOG) performance status 0–1, and 87% received CT + bevacizumab as first-line therapy. For patients who received 1LM niraparib, the median age was 68.5 years, 66% had Stage III cancer at index date, 88% had an ECOG performance status of 0–1, and 79% received chemotherapy alone as first-line therapy. Only 1 bevacizumab (BRCAm) and 11 niraparib (4 BRCAm, 7 BRCAwt HRd) patients had known homologous recombination deficiency (HRd)-positive tumors. Patients treated with bevacizumab had a median TTNT of 4.5 months (mo) and a 12-month OS mark of 83.6%; for patients treated with niraparib, the corresponding values were 9.9 mo and 96.3%. Conclusions: Our study provides real-world outcomes data for newly diagnosed AOC patients receiving maintenance niraparib or bevacizumab following CT +/- bevacizumab. HRd testing results were only available for 19% of bevacizumab- and 40% of niraparib-treated patients, highlighting a need for greater testing in the real world. Future studies should examine which patient characteristics are associated with long-term survival for these and other treatment options to aid in the decision-making process. Funding: GSK215281. [Table: see text]
PARPi monotherapy as first-line maintenance following chemotherapy + bevacizumab in advanced ovarian cancer.
Authors: Kudrik Fred J. , Vasudevan Anupama , English Sandy , Gart Mike , Oladipo Taofikat , Hartman John , Iadeluca Laura L. 
Published: June 2023

e17601 Background: Chemotherapy (CT) + bevacizumab is a standard-of-care option for first-line (1L) treatment for patients with advanced ovarian cancer (AOC). Real-world approaches to 1L maintenance (1LM) treatment include, among others, bevacizumab monotherapy or switching to poly(ADP-ribose) polymerase inhibitor (PARPi) monotherapy after completing 6–9 cycles of induction CT + bevacizumab. Methods: We identified 61 patients with AOC from the US-based, deidentified Integra PrecisionQ database who received 1LM bevacizumab monotherapy (n=27) or PARPi monotherapy (n=34) after 1L CT + bevacizumab initiated between July 1, 2019, and March 31, 2021, and followed them until the data cut-off of March 31, 2022. Using the start of 1LM therapy as the index date, we examined patient characteristics, time to next treatment or death (TTNT; often used as a real-world proxy for progression-free survival), and overall survival (OS) for these two treatment groups. Results: For patients who received 1LM bevacizumab, the median age was 69 years, 89% had Eastern Cooperative Oncology Group (ECOG) performance status 0–1, 63% had Stage III disease at index, and only 1 (4%) had a recorded/documented homologous recombination deficiency (HRd)-positive tumor. Of the 34 patients who switched to 1LM PARPi monotherapy, 21 (62%) received olaparib, 12 (35%) niraparib, and 1 (3%) rucaparib. The median age of these patients was 63.5 years, 94% had ECOG performance status 0–1, 62% had Stage III disease at index date, and 47% had HRD+ tumors. For patients who switched to 1LM PARPi monotherapy, the median TTNT was 10.8 months (mo) and 97% were still alive at the 12-month mark. For patients who continued with 1LM bevacizumab, the median TTNT was 4.9 mo and 81% remained alive at the 12-month mark. Conclusions: This study suggests that switching to maintenance with PARPi monotherapy following induction CT + bevacizumab is a viable option for the treatment of AOC. A higher prevalence of HRd patients switching to PARPi monotherapy may indicate clinician preference for PARPi monotherapy in biomarker-selected subgroups, and further analysis is needed to examine which patients are most likely to benefit from switch maintenance. Funding: GSK215281. [Table: see text]
OncoTherad immunotherapy plus platelet rich plasma as potential therapeutic strategy for ovarian cancer: The role of toll-like receptors 2 and 4 signaling pathways.
Authors: Oliveira Gabriela , Ribeiro de Souza Bianca , Lima Baggio de Paula Juliane , Henrique da Silva Santos Daniel , Camargo Gabriela Cardoso de Arruda , Fávaro Wagner José , Duran Nelson 
Published: June 2023

e17602 Background: Ovarian cancer (OC) has the most devastating death rate of gynecological cancers with only 44% of women surviving 5 years after diagnosis. Toll-like receptors (TLRs) signaling can play an important role in the OC treatment. TLR activation in immune cells can help activate an effective antitumor response. In this scenario, a new perspective is represented by combined OncoTherad (MRB-CFI-1) immunotherapy and Platelet Rich Plasma (PRP). OncoTherad (MRB-CFI-1) leads to the distinct stimulation of the innate immune system mediated by TLR2 and TLR4, resulting in an increased activation of the IFN signaling pathway. Also, PRP acts on immune activation and exerts antitumor effects. This study characterized the histopathological and molecular effects of the OncoTherad associated with PRP in the treatment of OC chemically induced in rats and described the possible mechanisms of action of this association involving the TLRs 2 and 4 signaling pathways. Methods: Fischer 344 female rats were divided into 5 groups (n = 7 animals per group): Control (Sham surgery) group; Cancer (7,12 dimethylbenzoanthracene – DMBA injection in the ovarian bursa, 1.25 mg/kg) group; OncoTherad (20mg/kg) group; PRP (328.103 – 549.103 platelets/mm3) group and; OncoTherad+PRP (same doses of the isolated treatments) group. Intraperitoneal doses were administered twice a week for 4 weeks. Immunohistochemistry was analyzed as total immunoreactivity and intensity of immunoreaction. Results: Our results showed serous type ovarian carcinoma, follicular atresia, absence of corpora lutea and hyperplasia of the germinal epithelium and tunica albuginea in the Cancer group. The histopathological changes in the PRP group were similar as Cancer group. In contrast, the animals treated with OncoTherad singly or in combination with PRP showed decrease of ovarian neoplastic lesions and histopathological recovery. TLR4 and IL-6 immunoreactivities were significantly lower (p < 0.05) in the Cancer group. PRP treatment reduced (p < 0.05) TLR2. In the Oncotherad+PRP group, the immunoreactivities of TLR4, MyD88, IRF-3 and TNF-α were lower. OncoTherad treatment alone led to stimulation of the innate immune system mediated by TLR2 and TLR4, resulting in an increased activation of the MyD88 signaling pathway (intensified IL-6 and TNF-α immunoreactivities). Conclusions: OncoTherad immunotherapy was able to reduce ovarian lesions and stimulated the TLR2 and 4 signaling pathways in the OC microenvironment, leading to antitumor effects by activating the production of inflammatory cytokines. Thus, OncoTherad immunotherapy could be considered an important therapeutic strategy for OC.
Serial monitoring of ovarian cancer risk in women with adnexal mass.
Authors: Pappas Todd C. , Ghosh Srinka , Reilly Gerard P. , Phan Ryan 
Published: June 2023

e17608 Background: Monitoring of ovarian malignancy risk in indeterminate masses is typically done using TVUS and other clinical factors. No biomarkers are available to assist physicians in clinical management of benign or indeterminate adnexal mass either on initial visit or in follow-up. We recently characterized the clinical performance of a deep neural network-derived multivariate index assay (MIA3G) [1] to assess ovarian malignancy risk in retrospective and prospectively collected multi-site clinical studies. Here we present data on MIA3G serial follow-up to monitor ovarian cancer risk in women presented with adnexal mass from the prospective studies. Methods: Data are presented from ongoing multisite clinical studies in which total 924 patients presented with adnexal masses were enrolled. Follow-up visits, scheduled at clinician’s discretion, may have included imaging and blood collection. Specimens were processed for serum and run on a clinical analyzer. MIA3G score from 0-10 was calculated using seven serum biomarkers coupling with patient age and menopausal status based on previously published neural network-based algorithm. MIA3G with NPV of 99.7% (CI:99.2–99.9) was used to risk stratify the patient with an adnexal mass into low probability of malignancy or indeterminate with a validated cut off at 5.0. For this analysis, MIA3G scores were binned into the following Zones: I (0-2.49), II (2.50 -4.99) and II (5.00-10.00). Results: Of 924 enrolled patients, 538 patients had completed clinical and biomarker data on initial study draw. Of these, 145 had at least one follow-up test and 31 had at least two follow-up test. Median duration to first follow-up test was 108 d (~3.6 mon), and median duration to second follow-up test was 272 d (~9.1 mon). Follow-up in 3 MIA3G score zones at the 0 -3.6 and 3.6 - 9.1 mon interval consistently showed 88% patients within zone I remained unchanged, whereas 12% of patients moved to zones II and III. In the 0 - 3.6 mon interval, the median change in MIA3G score from I to II was 2.25 (n = 9, range 0.54 - 3.52) and from I to III was 5.92 (n = 8, range 5.08-7.62 ). In the 3.6 - 9.1 mon testing interval, the median change in MIA3G score from zone I to II was 3.11 (n = 2, range 2.75 to 3.46) and the single patient change from I to III was 6.89. Across both testing intervals, 17%-50% of patients in zone II remain unchanged while approximately 25% patients had score increase to zone III. Importantly, 50% of patients in zone III remained unchanged in the absence of clinical intervention whereas 50% had MIA3G score reduction in association with clinical management. Conclusions: These results indicate that i) the serial follow-up with MIA3G is recommended to monitor the clinical status of the adnexal mass every 3 months, ii) MIA3G score changes of > 2.25 suggest clinical follow-up, and finally iii) the MIA3G is a suitable tool for the effectiveness of clinical management of adnexal mass. [1]: DOI 10.3389/fmed.2023.1102437.