bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accuracy of prostate imaging reporting and data system (PI-RADS v2) in the detection of prostate cancer (PCa).
Authors: Gill David Michael , Bishoff Jay , Lynch Steven C. , Foy Bridget , Evans Jaden D. , Haslem Derrick S. , Yeatman Timothy Joseph , McLean Logan 
Published: May 2020

e17604 Background: MRI-targeted biopsy is increasingly utilized over standard 12-core transrectal ultrasound (TRUS) biopsy for men with MRI-visible prostate lesions. Some clinicians defer biopsy for PI-RADS v2 category 1 and 2 lesions per the PRECISION Study (Kasivisvanathan et. Al, NEJM, 2018). The aim of this study was to independently validate the accuracy of PI-RADS v2 in detecting prostate cancer (PCa) when applied to MRI/US fusion-guided biopsies in an independent cohort of 156 patients from a large integrated community health system. Methods: Men undergoing MRI/US fusion-guided biopsy from 2016-2020 in the Intermountain Healthcare system were consecutively analyzed in this retrospective study. MRI were interpreted from four abdominal fellowship trained radiologists all with at least 5 years of experience. Fusion biopsies were performed by two urologists. Men were stratified into groups based on their PI-RADS v2 category 1-5. Biopsies were considered positive when Gleason ≥3+3. Results: A total of 156 men had 258 lesions for which they underwent MRI/US fusion-guided biopsies in the Intermountain Healthcare system from 2016 to 2020. The PCa detection rate for PIRADSv2 category 1-2 was 29.8%, category 3 32.6%, and category 4-5 37.6%. PIRADS v2 category 1, 2, 3, 4, and 5 yielded any PCa in 25, 15.9, 23.8, 53.1, and 66.7%, respectively (Table). PIRADS v2 category 1-2, 3, and 4-5 yielded any PCa in 16.8%, 23.8%, and 57.7%, respectively. Conclusions: PI-RADS v2 categories generally correlate with PCa detection rates, however, to avoid biopsy, the test must be both sensitive and specific, with low false negative rates. In our institution, we show that PI-RADS 1, 2, and 3 do not rule out the presence of PCa, and therefore should not be used as the sole factor in determining the need for prostate lesion biopsy. [Table: see text]
Predicting prostate cancer death among 98,994 veterans: Differences by race/ethnicity.
Authors: Janet Tate , Danciu Ioana , Justice Amy , Leapman Michael , McMahon Benjamin , Wadia Roxanne 
Published: May 2020

e17609 Background: Prostate cancer mortality is higher in Blacks than Whites, but existing prognostic indices fail to account for race/ethnicity. Using data from the national U.S. Veterans Affairs Healthcare System (VA), we compared prediction of prostate cancer death by race/ethnicity. Methods: Men with biopsy confirmed prostate cancer from 2002-2016 were included. We excluded those with lymph node or distant metastatic disease at diagnosis and those not classified as Non-Hispanic White (NHW), Non-Hispanic Black (NHB), or Hispanic (HSP). We set aside 20% for future validation. Cox models estimated hazard ratios (HR) for prostate cancer death, stratified by age and race/ethnicity. Each was adjusted for age, Gleason score, tumor (T) stage, PSA at diagnosis, and calendar year. Results: Among 98,994 veterans with localized disease, 64% were NHW, 30% were NHB, and 6% were HSP. At diagnosis, median age differed by race/ethnicity (NHW 66 [IQR 62-71] yrs.; NHB 63 [58-68] yrs.; HSP 66 [61-73] yrs.). During follow-up 23,316 men died, 3484 (15% overall, and by race/ethnicity) by prostate cancer. Among those < 65 yrs at diagnosis, HR for Gleason score were much stronger among NHW than NHB; associations for PSA level were stronger among NHB than NHW. HRs for HSP and NHW were similar. T stage HRs were similar by age and race/ethnicity. Conclusions: Risk associated with Gleason score and PSA varied by age and race/ethnicity. Prognostic models for prostate cancer disease progression must be evaluated in diverse populations and across age strata. [Table: see text]
Pattern of disease in recurrent cervical cancer associated with response to pembrolizumab.
Authors: Miller Kathryn , Filippova Olga T. , Hayes Sara A. , Abu-Rustum Nadeem , Aghajanian Carol , Broach Vance , Ellenson Lora H , Jewell Elizabeth Lin , Kyi Chrisann , Lakhman Yulia , Mueller Jennifer Jean , O'Cearbhaill Roisin Eilish , Park Kay J. , Sonoda Yukio , Zamarin Dmitriy , Leitao Mario M. , Friedman Claire Frances 
Published: May 2020

e18006 Background: Pembrolizumab received accelerated FDA approval for treatment of metastatic or recurrent PD-L1 positive cervical cancer in 6/2018. Since then, the clinical characteristics of patients who best respond to this immunotherapy have remained undefined. We sought to describe patients with advanced cervical cancer who derived durable clinical benefit (DCB) from pembrolizumab therapy. Methods: Patients with advanced or recurrent cervical cancer who received pembrolizumab from 8/2017-12/2019 at our institution were assessed. Reviewed data included patient demographics, treatment history, baseline pattern of metastatic disease at initiation of anti-PD-1 treatment, and outcomes. Kaplan-Meier survival analysis was performed to determine progression-free survival (PFS). Treatment response was evaluated by computed tomography using RECIST 1.1 criteria. Results: 14 patients with recurrent cervical cancer received pembrolizumab. Median age was 55 years (range, 21-76); 79% (n = 11) had squamous cell carcinoma (SCC). The 3 non-SCC histologies included endocervical adenocarcinoma, high-grade endometroid adenocarcinoma, and mesonephric adenocarcinoma. 93% (n = 13) expressed PD-L1; 1 patient whose tumor was MSI-H did not undergo PD-L1 testing. 93% (n = 13) had received prior radiation, and 86% (n = 12) had received 1 or more prior lines of chemotherapy. Median duration of treatment was 4.9 months (range, 1.4-15.2), and median follow-up was 7.9 months (range, 2.1-29.9). On RECIST review, the overall response rate was 21% (n = 3), including 2 partial responses and 1 complete response. Two patients (14%) had stable disease of ≥6 months for an observed DCB of 36%. Of the 5 patients with DCB, 4 remain on pembrolizumab, with observed antitumor activity of up to 15.4 months. On univariable analysis, a lymph node and/or lung only baseline pattern of metastasis was associated with improved response to pembrolizumab (n = 7, P= 0.02). On survival analysis, patients with lymph node and/or lung pattern of disease had a 6-month PFS rate of 86%, compared to a 6-month PFS rate of 0% in patients with visceral or multi-site disease ( P< 0.001). Conclusions: Pembrolizumab showed promising activity in our patient cohort, with a DCB rate of 33%. Patients with lymph node and/or lung only patterns of metastasis at baseline had the greatest radiologic response compared to patients with visceral or multi-site disease. Our results suggest that there may be an underlying pathophysiology of metastatic patterns that confer improved response to anti-PD-1 therapy in advanced cervical cancer.
Effect of the oral CXCR4 inhibitor X4-136 on tumor control and side effects in cervical cancer treated with radiotherapy and concurrent chemotherapy.
Authors: Chaudary Naz , Hill Richard (Dick) P , Kelley Lynne , Milosevic Michael F. 
Published: May 2020

e18010 Background: Cervical cancer is a global health problem. Despite scale up of prevention programs, there will be an ongoing need to improve the effectiveness of radiotherapy/cisplatin (RTCT) for women with established, locally advanced disease. We have shown that RTCT with the CXCR4 inhibitor plerixafor improves tumor control, reduces metastases and reduces RT-related side effects compared to RTCT alone. X4-136 is an oral CXCR4 inhibitor that is better suited to long-term, once daily use. In this study we examined: 1. The efficacy of RTCT and X4-136 in cervical cancer; 2. Biomarkers of response to RTCT and X4-136; and 3. Effects of RTCT and X4-136 on intestinal toxicity, an important dose-limiting RT side effect in these patients. Methods: Orthotopic cervical cancer xenografts derived from our patients were treated with RT (30 Gy; 2 Gy/day) and cisplatin (4 mg/kg/week ip) with or without concurrent X4-136 (100 mg/kg/day orally) for 3 weeks. Mice were sacrificed immediately after treatment for biomarker assessment. In separate experiments, mice had CT imaging weekly after treatment to evaluate tumor response. Acute and late intestinal toxicity was assessed histologically 3.5 and 90 days after treatment respectively. Results: RTCT alone increased CXCL12/CXCR4 signaling, intratumoral accumulation of myeloid cells and PD-L1 expression. The addition of X4-136 during RTCT abrogated these effects and improved tumor response in 2 cervical cancer models. Furthermore, the addition of X4-136 increased the proportion of surviving intestinal crypt cells in keeping with a reduction in acute RT toxicity, and reduced late histologic changes of late RT toxicity. Conclusions: The addition of X4-136 blunts RTCT-induced upregulation of the CXCL12/CXCR4 pathway, reduces intratumoral myeloid cells, improves tumor control and reduces side effects in cervical cancer. Few if any pharmacologic strategies have been identified previously that expand the therapeutic window with RT in this way. The combination of RTCT and CXCR4 inhibition warrants testing in clinical trials to validate these findings. These benefits may apply to other tumors where RTCT plays a curative role.
Ozone therapy as accompanying treatment for chemoradiotherapy in patients with locally advanced cervical cancer.
Authors: Rodionova Olga G. , Gusareva Marina A. , Voshedskiy Vitaliy I. , Vasilyeva Ekaterina O. , Sheiko Elena A. , Solntseva Anna A. , Sakun Pavel G. , Vlasov Stanislav G. , Museyko Ksenia N. , Pustovalova Alla V. , Chalabova Tatiana G. , Kit Oleg I. 
Published: May 2020

e18030 Background: Chemoradiation therapy (CRT) radiomodified with platinum-based drugs is recommended for patients with inoperable cervical cancer. However, the introduction of chemotherapy medicines increases the number of hematological and non-hematological complications. Prolonged RT significantly decreases survival of patients. This requires more effective methods helping to prevent chemoradiotherapy complications. The purpose of the study was to evaluate the effectiveness of ozone therapy as an accompanying treatment for chemoradiotherapy for cervical cancer (CC). Methods: The study included 20 patients diagnosed with cT3NхM0 CC. The control group (n = 10) received standard CRT with weekly cisplatin radiomodification (40 mg/m2). The main group (n = 10) received CRT with weekly cisplatin radiomodification (40 mg/m2) and additional infusions of 250 ml ozonized solution of 0.9% sodium chloride (a total of 15 infusions). Results: In the main group, CRT did not cause a significant aggravation of gastrointestinal and general symptoms, compared with the initial state. The rate of dyspeptic disorders (nausea, diarrhea, bloating) was 10% in the main group and 100% in controls. In the control group, clinical pain decreased only by the 25th day; 100% of patients developed gastrointestinal toxicity grade 1 (80%) and 2 (20%); 100% of patients complained of weakness during treatment. 7 patients developed leukopenia. Anemia in 5 patients remained at the level of 95g/L, in 3 patients - aggravation up to 80g/L. In the main group, treatment was completed within 7 weeks. In the control group, the duration of CRT was 8 weeks due to toxicity. Conclusions: Ozone therapy in addition to the conventional conservative treatment significantly decreases the severity of CRT-induced complications which allows complete treatment planned, while maintaining optimal treatment duration.
Recurrent vulvar squamous cell carcinoma: An analysis of clinical outcomes by treatment modality including surgery, chemotherapy, and radiation.
Authors: Dinh Trish , Andrews Wright Natalie , Iyer Hari , Weberpals Johanne I 
Published: May 2020

e18033 Background: Recurrent VSCC carries a poor prognosis, but real-world data on outcomes with standard treatment options are lacking. Specifically, progression free survival (PFS) in recurrent VSCC is ill-defined which is problematic for the design of clinical trials with novel therapies. We aim to address the paucity of outcome data in recurrent VSCC and to compare PFS and overall survival (OS) in patients (pts) undergoing surgery, chemotherapy, radiotherapy or a combination of these treatments. Methods: A retrospective chart review identified 246 pts from 2000-2018 diagnosed with VSCC treated at the Ottawa Hospital Cancer Center and 61 pts with recurrent disease. Data collected included patient demographics, tumour characteristics, recurrence pattern, and treatment modality (surgery only, surgery with chemotherapy, surgery with radiation, surgery with chemoradiation, chemoradiation only, chemotherapy only, or radiation only). Descriptive statistical analysis is reported. Results: Among all study pts, the stage distribution was stage I: 28%, II: 19%, III: 43% and IV: 10%. 61% of pts had one recurrence, 36% had two recurrences, and 3% had three recurrences. The 5-year survival rate was 78% for non-recurrent VSCC vs. 33% for recurrent cases. The median OS for all recurrent and non-recurrent cases was 3.7 years and 13.5 years, respectively. For primary treatment, 87% underwent surgical treatment, of which 60% also had radiation or chemoradiation. The most common treatments for first recurrence were: surgery (25%), radiation (20%), no treatment (16%) and chemotherapy (14%), and for second recurrence: no treatment (50%), radiation (25%), surgery (17%) and chemotherapy (8%). The median PFS after primary treatment and after first and second recurrences were 8.7, 5.3 and 1.4 months (mo), respectively, with no significant difference between treatment regimens. However, when grouped (surgery with or without chemotherapy, radiation or chemoradiation vs. non-surgical management), there was a significant PFS benefit for surgical (15.6 mo) over non-surgical management (0.7 mo) in the treatment of a second recurrence (p = 0.05). Conclusions: At our centre, surgery and radiation have been the mainstay of treatment for recurrent VSCC with particular advantage of surgery in the treatment of a second recurrence. Our study establishes a baseline for VSCC outcomes following standard treatment. Accurate PFS data is an important outcome for the design of future studies in recurrent VSCC with new drug therapies.
A CD3 x FRα T-cell engaging bispecific antibody for efficient killing of ovarian cancer cells with minimal cytokine release.
Authors: Buelow Ben , Avanzino Brian , Balasubramani Aarti , Boudreau Andrew , Davison Laura , Ganesan Priya , Harris Katherine , Hartstein Sharon , Malik-Chaudhry Harbani , Pham Duy , Prabhakar Kirthana , Rangaswamy Udaya , Saiganesh Sowmya , Schellenberger Ute , Ugamraj Harshad , Kehm Hannes , Trinklein Nathan , Iyer Suhasini 
Published: May 2020

e18050 Background: Ovarian Cancer (OvCa) is the leading cause of gynecologic cancer mortality in women. Since the introduction of platinum-based chemotherapy there has been little change in the prognosis of OvCa patients, with < 30% overall survival in advanced disease, creating an urgent medical need for novel therapies. Few ovarian epithelium-specific surface proteins are suited for Ab targeting. However, studies have shown folate receptor α (FRα) to be highly over-expressed in OvCa; expression level and stage correlate, and FRα is absent or minimally expressed in normal tissues. However, naked Ab therapy has shown limited efficacy while CAR-T therapy has been plagued by toxicity and limited efficacy. ADCs have demonstrated some activity but present the risk of toxin-mediated side effects. Using Teneobio’s unique antibody discovery platform, we have developed a CD3 x FRα T-BsAb that retains the potent cytotoxicity of other T-cell redirecting therapies but with significantly reduced cytokine release. Methods: Antibodies targeting CD3 and FRα were generated via immunization of our proprietary transgenic animals. Candidate antibodies were selected by repertoire deep sequencing of B-cells from draining lymph nodes, high-throughput gene assembly, recombinant expression, and functional screening. Bispecific antibodies targeting CD3 and FRα were assembled and evaluated for their ability to selectively activate primary human T-cells and mediate killing of FRα+ tumor cells in vitro and in vivo. T-cell activation surface markers, cytokine production and tumor cell cytotoxicity were measured. Results: Primary human T-cells were activated only in the presence of both the CD3 x FRα T-BsAb and FRα (either recombinant or cell-surface protein). Potent and selective cytotoxicity against FRα+ tumor cells was observed in co-cultures of primary human T-cells and OvCa tumor cell lines. Strikingly, our T-BsAb mediated comparable tumor cell cytotoxicity to CD3 x FRα T-BsAbs containing a high affinity anti-CD3 domain but with significantly reduced cytokine production. Our Ab showed preliminary evidence of tumor growth inhibition in xenograft models of OvCa in vivo. Conclusions: We have created a novel CD3 x FRα T-BsAb that mediates T-cell killing of FRα+ tumor cells with minimal production of cytokines. This molecule may improve safety, efficacy, and offer opportunities for combination therapy to treat OvCa.
FSCN1 as prognostic marker in borderline tumors of the ovary.
Authors: El-Balat Ahmed , Holtrich Uwe , Karn Thomas , Becker Sven 
Published: May 2020

e18061 Background: Risk factors for invasive recurrence of borderline tumours (BOT) of the ovary are needed. The actin-bundling protein Fascin-1 (FSCN1) is involved in alteration of adhesion and cell motility and has been associated with invasion and metastasis in different cancers. Methods: We studied a retrospective cohort of 124 bordeline tumors of the ovary (BOT) with validated diagnosis by an independent pathologist for expression of FSCN1 as potential prognostic biomarker. Results: We found strong expression of the actin-bundling protein FSCN1 in 62 of these tumors. FSCN1 positive patients were slightly younger (46.9±2.2 vs. 53.3±2.3 years, P = 0.049). Expression of FSCN1 was more frequently detected in BOT with serous compared to mucinous histotype (58/78 [74.4%] vs. 3/41 [7.3%], p < 0.001), and in cases with micropapillary pattern (25/28 [89.3%] vs. 38/98 [38.8%], P < 0.001). In addition, a non significant trend was observed for more frequent expression of FSCN1 among cases with implants (8/10 [80.0%] vs. 55/116 [47.4%], P = 0.095). When we compared progression free survival of the patients we found numerical lower but not statistically significant PFS rates of 90.5±6.4% vs. 94.4±5.4% for 10 years, and 81.4±10.3% vs. 94.4±5.4% for 15 years, in BOT with FSCN1 expression compared to those tumors negative for FSCN1, respectively. Conclusions: Our analysis suggests an association of FSCN1 expression in BOT with micropapillary pattern and implants, which have been linked to inferior prognosis. Cases with FSCN1 expression in our cohort displayed numerical lower PFS rates prompting further studies of this marker.
Efficacy of dose-dense chemotherapy as first-line treatment of advanced ovarian cancer patients after non-optimal debulking.
Authors: Rumyantsev Alexey , Tyulyandina Alexandra , Pokataev Ilya , Morkhov Konstantin , Nechuskina Valentina Mikhailovna , Tjulandin Sergei 
Published: May 2020

e18066 Background: Patients with advanced ovarian cancer have unfavorable prognosis after primary debulking surgery if the size of residual tumor exceeds 1 cm. The optimal approaches to systemic treatment of these patients remain unknown. We evaluated the efficacy and safety of dose-dose chemotherapy in frontline treatment of ovarian cancer patients after upfront non-optimal debulking surgery. Methods: This was a non-randomized single-arm phase II trial. We enrolled patients with advanced (FIGO III-IV) epithelial ovarian who underwent non-optimal upfront debulking surgery with residual tumor size > 10 mm. All patients were treated with dose-dense chemotherapy (ie, paclitaxel 80 mg/m2 day 1, 8, 15 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles). Patients in historical control arm received standard chemotherapy with paclitaxel 175 mg/m2 day 1 + carboplatin AUC6 day 1, cycled every 21 days – 6 cycles. No patient in experimental or control arm received front-line bevacizumab or PARP inhibitors. The primary endpoint of the trial was progression-free survival (PFS). According to the historical data of our department, 1-year PFS in this category of patients equals to 51%. To increase 1-year PFS to 70%, 40 patients should be enrolled with α = 0.05 and β = 0.20 and estimated data loss for 10% of patients. Results: The study enrolled 40 patients to dose-dense chemotherapy arm, control arm included 86 patients. The trial arms were balanced in terms of age, performance status and other characteristics. Median follow-up was 28.8 months. The 1-year PFS was 76.9% compared to 51% in historical arm, median PFS was 19.8 months and 12 months respectively (HR 0.61; 95% CI 0.39-0.95; p = 0,03). The 1-year overall survival rate was 92.3% with median OS not reached with specified follow-up period. Severe neutropenia, anemia, thrombocytopenia was observed in 82.1%, 53.8%, 15.3% of patients, respectively. Conclusions: The results of the study showed high efficacy of dose-dose chemotherapy as front line of treatment for advanced ovarian cancer patients after non-optimal upfront debulking surgery but one should consider high toxicity of this regimen.
Anlotinib (AL3818) plus pemetrexed in patients with recurrent platinum-resistant advanced epithelial ovarian cancer: A single-arm, open-label, phase II study.
Authors: Zhang Yanna , Chen Jueming , Wei Wei , Zheng Lie , Li Han , Feng Yanling , Wan Ting , Qiu Jiaqi , Jiang Xingyu , Xiong Ying , Li Jundong , Song Libing , Liu Jihong , Huang He 
Published: May 2020

e18078 Background: Anlotinib (AL3818) is a novel multi-target tyrosine kinase inhibitor that has previously shown clinical antitumor activity in various cancers, including the phase I study on tumors of female reproductive system. This phase II study (ChiCTR1800018192) aims to further evaluate the safety and efficacy of anlotinib combined with pemetrexed in patients with recurrent platinum-resistant advanced epithelial ovarian cancer. Methods: Patients who underwent cytoreductive operation, with histopathologically advanced epithelial ovarian cancer ( FIGO staging III or IV), and failed to previously platinum-based chemotherapies were considered eligible for enrollment to receive combined treatment of anlotinib (12 mg per day, days 1-14; 21 days per cycle) plus pemetrexed (0.5 g/m2, day 1; 21 days per cycle). Total duration of combined treatment contained 6 cycles, and subsequent maintenance treatment was anlotinib monotherapy (12 mg per day, days 1-14; 21 days per cycle) till disease progression or intolerant toxicity. The primary endpoint of this study was objective response rate (ORR) and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and safety. Results: Between 2018 July and 2019 October, 13 patients (female) with a median age of 55 years (range: 41 - 65), FIGO histopathological stage IIIA (7.7%) or IIIC (76.9%) or IV (15.4%) were enrolled. Over a mean follow-up period of 5.9 (95% CI: 3.4-8.3) months, therapeutic evaluation showed the incidence of partial response, stable disease, and progression disease was 38.5%, 53.8% and 7.7% respectively, yielding the ORR of 38.5% (5/13; 95% CI: 13.9%-68.4%) and the DCR of 92.3% (12/13; 95% CI: 64.0%-99.8%). The median PFS was not reached. Frequently occurring adverse events (AEs) were grade 1 or 2, including hand-foot syndrome (53.8%), allergic eruption (38.5%), mild hypertention (30.8%), fatigue (23.1%), diarrhea (23.1%), gum-pain (15.4%), and dry cough (15.4%). High grade AE was only observed in 1 patients with hemoglobin reduction of grade 4. Neither unexpected safety signals nor treatment related death occurred. Conclusions: Anlotinib (AL3818) plus pemetrexed showed a promising activity with an acceptable safety profile for previously platinum-treated patients with recurrent advanced epithelial ovarian cancer. Clinical trial information: ChiCTR1800018192.