bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new perspective of different schemes of neoadjuvant chemotherapy followed by concurrent chemotherapy and radiotherapy for locally advanced cervical cancer.
Authors: Tian Xue , Li Fenghu , Li Ran , Yang Feiyue , Chang Jianying , Li Jiehui , Hu Lili , Du Yanjun , Mei Fan , Zuo Kai , Chen Shuying 
Published: May 2020

e18011 Background: To observe the clinical effect, survival time and toxicity and side effects in unoperated cervical cancer patients treated with different schemes of neoadjuvant chemotherapy (NACT) followed by concurrent chemotherapy and radiotherapy (CCRT). Methods: A retrospective analysis was performed in 120 patients who were followed up until they died or being followed up at least 5 years. The treatment schedules consisted of 2 cycles of intravenous paclitaxel 135-175 mg/m2 plus cisplatin 60-80mg/m2 (TP group, 62 patients) or lobaplatin 30mg/m2 (TL group, 58 patients) every 21 days. Patients were then submitted to CCRT. Chemotherapy regimen of CCRT was cisplatin 40 mg/m2 (TP group) or lobaplatin 30mg/m2 (TL group) weekly. External beam radiation therapy (total 50.4-56.35Gy, 28 fractions, 180-215cGy per fraction daily) was administered using the3D-CRT or IMRT followed by intracavitary brachytherapy (5Gy per fractions, mostly 5 fractions, Ir192 based). Results: The proportion who had a complete/partial response was 81.7% after NACT, and 99.2% after all treatment. In all patients, the one-year, three-year and five-year survival rates were 99.2%, 81.7% and 69.2% respectively. In TP group vs. TL group, the 3-yr and 5-yr survival rates were 85.5% vs.77.6% (χ2= 1.248, p = 0.264) and 75.8% vs. 63.8% (χ2= 2.059, p = 0.151) with no significant difference. In mass size ≥ 5cm group vs. <5cm group, 3-yr survival rates were 88.0% vs.77.1% with no significant difference (χ2= 2.296, p = 0.130), but 5-yr survival rates were 82.0% vs.61.4% (χ2= 5.878, p = 0.015) with significant difference. The 3-yr and 5-yr OS rates between stage IIB and stage IIIB were not significantly different, respectively 83.1% vs. 70.6% (χ2= 2.083, p = 0.149) and 67.7% vs. 64.7% (χ2= 0.090, p = 0.765) . In TP group, grade 3 or 4 digestive reaction was obviously more frequent than TL group, respectively 54.3% vs. 1.8%(p = 0.000). Neutropenia and thrombocytopenia are more common in TL group than TP group, respectively 48.3% vs. 30.6%(p = 0.0.048) and 44.8% vs. 1.6%(p = 0.000). Conclusions: For patients with severe digestive system reaction or contraindications of cisplatin, lobaplatin was might be used as an alternative drug. A prospective research is undergoing in our hospital. NACT may improve the prognosis of patients with large-scale mass. A undergoing prospective study protocol was approved by the Ethics Committee of hospital number 2017-02 and was registered in ClinicalTrial.gov as ChiCTR-IIR-17011559.
Opportunities and challenges in cervical cancer screening program in Kazakhstan: Results after imPACT review.
Authors: Kaidarova Dilyara , Bolatbekova Raikhan , Zhylkaidarova Alma , Sadykova Tolkyn , Kukubassov Yerlan , Aidarov Askar , Satanova Alima 
Published: May 2020

e18020 Background: Cervical cancer is the second most common cancer in women worldwide, where the majority of registered patients are in developing countries. Screening programs in developed countries have reduced morbidity and mortality from cervical cancer by more than 2 times. Cervical cancer (CC) is the most common gynecological cancer in Kazakhstan (KZ). Standardized incidence rate of CC was 18.2 per 100,000, while the mortality rate was 6.2 per 100,000, in 2019. The National Cervical Screening program in KZ uses cytology (Pap test) from 2008. Screening program funded by the State budget. In 2016, Experts of imPACT Mission analyzed the CC screening and made recommendations for improvement. Since 2018 target age of CC screening expanded to 30-70 years and shortened the interval to 4 years, strengthened the control of patients with pre-cancerous pathology. Until 2018, people came to a fixed age; today we start CC screening within the target age at any age at the time of the first visit. The purpose of this study is to analyze cytological screening results in KZ after imPACT recommendations. Methods: Coverage, the number of screened women, the level of pre-cancer detection and cervical cancer during screening have been obtained from specific reports (form № 025, № 08) for 2008-2019. Results: The total number of screened women was in 6.775.975. There is a decrease in the number of screened women by 32% from 2008 to 2017. Since improvement of CC screening we increased coverage from 49.9% in 2017 (abs. number 409.124) to 89% in 2019 (abs. number 954.322). According to the results of screening, 2603 cases of CC were registered in 12 years. Analysis of screening results showed a marked increase in the detection of CC with an increasing by 67%. The persentage of registered cases of ASH+HSIL increased from 0.136% to 0.673%. Conclusions: there has been an increase in the coverage by screening of the target population since the screening update. During the study period, there has been an improvement in the detection of precancerous pathology and cancer in the early stage. Despite the positive results of screening, sufficient coverage by screening, certain successes in detecting the initial stage of CC, mortality rate from CC remain high, which makes it necessary to improve the screening of CC in KZ through the introduction of HPV-screening.
Non-brachytherapy approach for locally advanced cervical cancer treatment.
Authors: Salim Nidal , Nosov Vladimir , Zvereva Daria , Novikova Olga , Tedeeva Anna , Trofimenko Irina , Gromova Nadezhda , Koposov Pavel 
Published: May 2020

e18023 Background: Concomitant chemoradiation therapy (CRT) that includes both external beam radiotherapy (EBRT) and brachytherapy (BT) is the current standard of care in treatment of locally advanced cervical cancer (LACC). Adaptive EBRT using volumetric modulated arc technology without BT allows dose escalation and decreases toxicities. Non-brachytherapy treatment is an evolving alternative approach provides geographical radiation accuracy but the oncological outcomes still to be evaluated. Methods: Patients with LACC (stages 1B3–IVA) who underwent non-brachytherapy CRT using adaptive EBRT with simultaneous integrated boost at our institution were evaluated prospectively from May 2015 to December 2019. All patients were initially assessed by a gynecologic oncologist, pelvic MRI and 18FDG-PET/CT scan were conducted. Follow-up pelvic examinations with cytology every 3 months and PET/CT at 3 and 12 months after completion of treatment were performed. Oncological outcomes and toxicities were assessed. Results: Twenty-one patients were analyzed: median age was 54 years (30–76 years); 19 patients had squamous cell histology and 2 had adenocarcinoma. Median follow-up was 32 months (8–56). The average dose administered to the gross tumor volume was 90.2 Gy (79.5–96.6), 79.8 Gy to all PET/MRI positive lymph nodes (63.0–89.7). No patents received BT; all but 3 received chemotherapy. Three-year local control was 100% (PFS = 90.4% and OS = 100%). There were 2 recurrences: a solitary skull lesion 18 months following CRT in a patient with mesonephric adenocarcinoma and a metastasis to a transposed ovary 15 months after CRT. No grade 3–4 toxicities were seen. Only 1 patient (4.7%) had late rectal grade II toxicity. Conclusions: Non-brachytherapy adaptive CRT for LACC is feasible. It allows for a significant dose escalation, thus providing better local control and likely increases PFS and OS at no cost of serious toxicity. Randomized studies comparing this approach to the current standard of care are needed.
Uncovering the immune-modulating role of anti-RANKL therapy for cervical cancer: Preliminary results.
Authors: Van Dam Peter , Verhoeven Yannick , De Waele Jorrit , Jacobs Julie , Van Dam Pieter-Jan , Kockx Mark , Van de Vijver Koen , Lammens Martin , Wouters An , Smits Evelien , Lardon Filip , Trinh Xuan Bich 
Published: May 2020

e18028 Background: Conventional treatments for cervical cancer (CC) have reached a plateau and only limited progress for targeted therapy has been made over the last decades, resulting in a meager five-year survival rate of only 17% for the advanced stages. To improve long-term benefits for the patient, a promising hot field of research in oncology that opens new perspectives is immunotherapy. Even though CC has shown to be immunogenic, only a minority of patients respond to this type of treatment. In recent years, the RANKL/RANK signaling pathway has been implicated as a key immune modulating factor in the tumor microenvironment, allowing the cancer cells to evade the immune response by disrupting the immune-intrinsic crosstalk. Both RANKL and RANK are highly co-expressed in CC, which correlates with inferior clinicopathological parameters and an increased risk of death. Targeting this pathway may therefore be of great value in the treatment of CC and the quest to release the brakes on the immune system, thereby reinvigorating the tumors’ susceptibility to immunotherapy. Hence, we aim to elucidate the effects of anti-RANKL therapy on the tumor-immune microenvironment in CC. Methods: Two cervical biopsies were taken before and after anti-RANKL therapy in CC patients. One fresh biopsy was immediately processed to a single cell suspension for flow cytometry (FCM) using enzymatic digestion, while the other was formalin-fixed and paraffin-embedded for immunohistochemistry (IHC) and RNA sequencing. For FCM and IHC, the samples were stained with different markers for RANK/L signaling, the immune infiltrate and immune checkpoints. FCM was performed on a BD FACSAria IIä cytometer and analyzed with FlowJo. IHC staining was performed on a Ventana Benchmark Ultra and Ventana Discovery Ultra and scored by a pathologist or by HistoScientist using Visiopharm, while RNA sequencing was performed with the Truseq RNA exome panel on the NextSeq 500 system. Results: Our preliminary results show a relative increase of the CD8+ population, while a trend is observed in increased lymphocyte activation after anti-RANKL therapy. Updated results will be presented in more detail at the conference, including RNA sequencing data. Conclusions: Preliminary findings indicate that anti-RANKL therapy modifies the tumor-immune microenvironment in CC. Higher patient accrual will allow to dissect targets for combination therapy with anti-RANKL to further optimize this treatment strategy.
Open label phase I trial using SPL-108 in combination with weekly paclitaxel final report with molecular correlates.
Authors: Girda Eugenia , Hou June YiJuan , Buckley De Meritens Alexandre , Stephenson Ruth , Leiser Aliza L. , Song Mihae , Finlayson Malcolm , Nelson David M , Rodriguez-Rodriguez Lorna 
Published: May 2020

e18040 Background: Therapeutic options for patients with recurrent platinum resistant ovarian cancer are scarce and represent an unmet need in ovarian cancer. Chemotherapy resistance has been linked to many CD44 pathways including P-glycoprotein mediated efflux of chemotherapeutic agents. Our working hypothesis was that chemotherapy resistant ovarian tumors that expressed CD44 would revert drug resistance by using a CD44 inhibitor SPL-108, that had proven safe as a single agent. Methods: Patients with platinum refractory or resistant CD44+ ovarian tumors were eligible. We used a standard 3+3 phase I design, open-label, 2-arm trial of the combination of SPL-108 and IV paclitaxel (PTX): Arm 1 (2 cohorts) Safety Phase: Cohort 1: SPL-108 150 mg SQ Daily +80 mg PTX weekly Cohort 2: SPL-108 300mg daily +80 mg PTX weekly Arm 2 (1 cohort) Exploratory Phase: Cohort 3: SPL-108 daily dose 300 mg +80 mg PTX weekly Days 1-15 in 28 day cycles Primary end points were safety and tolerability. Secondary endpoints included determining molecular signatures of response using NGS. Tumors were sequenced at the time of recurrence or initial diagnosis. Results: Fourteen patients were enrolled in the study. Prior number of treatments ranged from 2-6, except for one patient with platinum refractory disease that progressed during first line of therapy. There was no DLT and all cohorts were completed as designed. The treatment was well tolerated. There was one instance of a bowel micro-perforation that was treated medically. This patient had platinum refractory disease and eventually underwent an interval cytoreduction. There was one patient with grade 3 neurotoxicity. Sixty-two% of the patients had clinical benefit with 36% having a PR. Forty-three % of patient had a PFS of more than 6 months. Two patients enjoyed a PR of 12 months. Molecular profiling of the tumors revealed that all tumors had TP53 alterations and the 4 patients that did not have a response had tumors with TP53 truncations or a lack of function alteration. Conclusions: Daily SPL-108 300mg SQ in combination with weekly PTX is safe and feasible. The promising clinical activity on drug resistant ovarian tumors warrants further investigation. Resistance to SPL-108 are characterized by lack of function of TP53, mostly early truncations. It is possible that SPL-108 may be reactivating TP53 by promoting its active conformation. Once TP53 is active CD44 expression is abrogated at the promoter. Therefore SPL-108 is effectively acting on CD44 through 2 different mechanisms to promote chemotherapy sensitivity. Clinical trial information: NCT03078400.
Results of a deep-dive survey on practice patterns of oncologists and advanced practice providers utilizing PARP inhibitors as maintenance therapy for patients with ovarian cancer.
Authors: Turell Wendy , Ackbarali Tariqa , Coleman Robert L. , Westin Shannon Neville , Smith Judith Ann 
Published: May 2020

e18044 Background: Often diagnosed at an advanced stage, most patients with ovarian cancer will relapse. As several PARP inhibitors (PARPi) have recently been approved as maintenance, patients are presented with treatment options that extend the interval of disease remission. However, novel challenges exist as oncology teams are apprehensive of integrating PARPi in practice. Emphasis on building this competence is essential for patients to obtain the maximum benefit of maintenance PARP therapy. Methods: Oncology teams were invited to participate in a 1-hour live and online education activity broadcast from 2018-2019 at OMedLive.com for 12 months. The activity addressed clinical data on the use of PARPi as maintenance therapy, management of adverse events, and emerging strategies utilizing PARP inhibition. A deep-dive survey, including structured and open-ended questions, was conducted 2 to 4 months after participation and focused on changes in practice, barriers to change, and observed patient outcomes. Results: In total, 915 clinicians participated in the video-based activity. Sixty physicians and advanced practitioners opted to complete the deep-dive survey, 70% of whom have used PARP inhibitors as maintenance therapy. Practice improvements were reported for identifying patients likely to benefit from PARPi (90%), differentiating among approved PARPi (86%), counseling patients (85%), and team-based side effect management (95%). The top 3 barriers to utilization of PARPi were lack of reimbursement (23%), inability to anticipate patient outcomes (15%), and unfamiliarity with clinical guidelines (15%). Variations in responses to open-ended questions included persistent questions (n = 47) in need of responses before adopting PARPi, data needed to better inform decision-making (n = 49), major concerns about PARPi (n = 55), and the most challenging aspects of current patient management with PARPi (n = 39). Conclusions: Patient education yielded improvements in practical application and management of PARP inhibitors for patients with ovarian cancer. The thematic variations in open-ended responses may inform the design of tailored interventions to improve clinical integration of PARP inhibitors as maintenance therapy and different lines of treatment.
Phase II study of intraperitoneal submicron particle paclitaxel (SPP) plus IV carboplatin and paclitaxel in patients with epithelial ovarian cancer undergoing cytoreductive surgery.
Authors: Mullany Sally Anne , Miller David S. , Robison Katina , Levinson Kimberly , Lee Yi-Chun , Yamada Seiko Diane , Walker Joan L. , Markman Maurie , Marin Alyson , Mast Peter , Dizerega Gere 
Published: May 2020

e18046 Background: Although advances in chemotherapy, cytoreductive surgery, and maintenance therapy (SOC) improved PFS for high grade epithelial ovarian cancer, > 20% of patients relapse during the first 6 months and 60% relapse after 6 months. Submicron particles (~800 nm) of paclitaxel (SPP) contain 1-2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. In a previous trial, percutaneous instillations of SPP in nonsurgical patients with intraperitoneal cancer were associated with reduced systemic and local toxicity as compared to standard chemotherapy regimens. (Williamson et al Cancer Chemo Pharm (2015) 75:1075). Methods: This study compared two dose-levels of IP SPP instilled in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment-emergent adverse events. Clinical response was determined by CT scans and serum CA-125 measurements. Results: Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m2 and three received 200 mg/m2. For analysis purposes, 7 out of 10 subjects were evaluable (1 withdrew, 1 died unrelated to study drug during IV treatment and 1 was unevaluable). Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment, but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. Conclusions: This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas. Clinical trial information: NCT03029585.
Factors affecting recurrence rates in women with borderline ovarian tumors.
Authors: Scanlon Lauren , Goldberg Gary L. 
Published: May 2020

e18055 Background: Borderline or low malignant potential tumors of the ovary (BOTs) make up approximately 15-20% of all ovarian neoplasms. These tumors are considered indolent and usually confer an excellent overall survival in women who are treated utilizing a conservative surgical approach. However, recurrence rates can approach 30%. The aim of this study was to compare the type and mode of surgery and its impact on outcomes in patients with BOTs. Methods: An Institutional Review Board approved, retrospective cohort study identified all patients at Long Island Jewish Medical Center, North Shore University Hospital and USC Medical Center with BOTs who underwent surgery between January 2008 and May 2018. Demographics and outcome measures were obtained from the medical records. Prognostic factors for disease recurrence were studied including histological subtypes type of surgical procedure, including minimally invasive or open ovarian cystectomy and oophorectomy. Results: 260 patients were identified. 226 of these women (88%) had stage I disease at the time of diagnosis. There were 26 recurrences noted in the cohort, a recurrence rate of 10 percent. The median age was 50 years old (range 16-86). 145 patients (56%) underwent minimally invasive surgical procedures compared to 115 (44%) who had open laparotomy. 30 (12%) of the women underwent an ovarian cystectomy and 230 (88%) had an oophorectomy. The median time to disease recurrence was 25 months (range 4-94 months). There was significant difference in the recurrence free survival between the patients who had minimally invasive procedures and those who had open laparotomy (hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.11-6.52). There was also significant difference in Recurrence Free Survival (RFS) and in those who underwent ovarian cystectomy and oophorectomy (HR 7.32, 95%CI 3.34-16.06). No difference in recurrence rates were noted between those with serous and mucinous histology. Conclusions: In this cohort of women with BOTs, the risk of recurrence was associated with minimally invasive surgery versus open laparotomy as well as ovarian cystectomy compared with oophorectomy. Conservative surgery for BOTs in young patients plays an important role for fertility preservation in these young women and can be curative. This study allows us to present additional information to address surgical approach and risk for disease recurrence in young women having fertility sparing and conservative surgery for BOTs.
Evaluation of adaptive NK cells in ovarian cancer patients with cytomegalovirus (CMV) reactivation and systemic inflammation.
Authors: Wesley Erin , Uppendahl Locke , Felices Martin , Messelt Audrey , Hunter-Schlichting Devon , Nelson Heather , Bendzick Laura , Geller Melissa Ann 
Published: May 2020

e18062 Background: Cytomegalovirus (CMV) is a common infection associated with increased inflammation (c-reactive protein (CRP) upon reactivation during immunosuppression. CMV infection has been associated with a subset of NK cells (adaptive) that are long-lived, have enhanced cytotoxicity, and thought to contribute to cancer control. Previous evaluation of a retrospective study showed CMV+CRP+ patients had significantly worse RFS and OS compared to CMV+ CRP− patients who had the longest OS. These findings suggest CMV may be immunomodulatory and, without immunosuppressive effects of inflammation, may be protective. We are further evaluating for the presence of adaptive NK cells in the patients to evaluate if these populations of cells are drivers for the changes in outcomes. Methods: Serum and ascites (22 samples each) collected in a prospective study at the time of surgery for HGSOC were evaluated for CMV and inflammation. CMV status and systemic inflammation were measured by immunoassay for CMV immunoglobulin G (IgG), dPCR for CMV DNA and C-reactive protein (CRP). Samples were categorized as reactive or non-reactive for CMV and positive or negative for CRP (≤10, > 10 mg/L). Adaptive NK cell percentages were analyzed using GraphPad Prims 8 and p-values ≤ 0.05 were considered statistically significant. Proteomic techniques to quantify adaptive NK cells, differences in NK cell maturation and cytotoxicity are in process for an additional 80 samples. Results: CMV reactive patients showed increased percentages of adaptive NK cells (NKG2C+CD57+) in the blood and peritoneal cavity compared to CMV negative patients. There is a trend in the presence of adaptive NK cells in patient samples that are CMV reactive and CRP positive compared to CMV nonreactive and CRP positive. Conclusions: Preliminary analysis shows a trend in presence of adaptive NK cells in both the blood and peritoneal cavity of these patients but analysis is ongoing.