bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with extended survival for patients with platinum-resistant ovarian cancer treated with modified vaccinia oncolytic virotherapy.
Authors: Manyam Madhavi , Stephens Amanda J. , Kennard Jessica A. , Fitzsimmons Christine K. , Kendrick James Erasmus , McKenzie Nathalie Dauphin , LeBlanc Jane , Smith Jamie L. , Ahmad Sarfraz , Holloway Robert W. 
Published: May 2019

e17070 Background: VIRO-15 phase IB trial included 11 patients (pts) with platinum-resistant ovarian cancer (PROC), extensive tumor burden and a median of 5 prior lines of therapy who were given intra-peritoneal Olvi-Vec (GL-ONC1), a modified vaccinia oncolytic virus (OV). Four pts had apparent clinical benefit with > 5 mos progression-free survival (PFS) following OV. This analysis aimed to determine factors that predict clinical benefit from OV. Methods: Comparative analyses included: anti-vaccinia neutralizing antibody (NA) as a measure of immune-competence, virus-encoded glucuronidase activity (GA) indicating viral replication, tumor shrinkage by RECIST 1.1, tumor burden (serum LDH), PD-L1 status, Prognostic Nutritional Index (PNI), absolute lymphocyte count, C-reactive protein, albumin, ECOG performance score (PS), no. of prior lines of therapy and platinum therapies, BRCA status, CA125 tumor marker, & circulating tumor cells (CTCs). Results: Mean age was 66.3±9.3 years and BMI 24.8±4.7 kg/m2. Median prior chemotherapy lines = 5 (range 2-10), median prior platinum lines = 3 (range 2-6), and 9 pts had prior Avastin. Following OV, 4 pts (Group A) had mean PFS 10.9±5.1 (range 5.4-16.4) mos compared to 7 pts (Group B), with mean PFS 2.4±1.1 (range 1.3-4.1) mos ( p< 0.05). Mean OS for Group A was 21.7±8.2 (range 7.8-28.3) mos vs 3.6±1.5 (range 1.6-6.2) mos for Group B ( p< 0.05). 3 Group A pts are alive with PS 0, and one with stable disease died at 8 mos from pulmonary embolism. Factors that predicted clinical benefit were: i) PNI [mean 49.0±5.7 vs 42.1±4.3 ( p< 0.05)], ii) Week-5 CA125 values < Week-2 [4/4 vs 0/7 (p < 0.01)], iii) absence of CTC [3/4 vs 1/7 pts ( p< 0.05)]. Baseline PD-L1 expression and BRCA status were not predictive markers. Conclusions: Factors associated with clinical benefit using GL-ONC1 monotherapy in PROC include PNI > 44.5, absence of CTCs, and Week-5 CA125 less than Week-2 levels. Absent these factors, cytotoxic therapy should be considered by Week-6 following GL-ONC1. Three patients are currently alive at 22.8-28.2 mos, following additional therapies. A multi-institutional phase II trial is currently enrolling. Clinical trial information: NCT02759588.
A 3D micro-tumor model capturing tumor heterogeneity of a patient's primary tumor biopsy.
Authors: Nikolov Katya , Sampson Ellen , Apfel Christian 
Published: May 2019

e17076 Background: Cancer is a genetic disease. However, because of the randomness of mutations, less than 20% of patients have known driver mutations and it is estimated that in the United States, less than 5% of patients benefit from genome-driven targeted therapy. [1] Thus, treatment for millions of cancer patients is still today a hit or miss experiment. Therefore, we have developed a developed a genome-free and mechanism agnostic 3D micro-tumor platform (SAGE Direct Test™) to help oncologists and patients alike to directly identify the treatment that is most effective for an individual patient. Methods: The SAGE Direct Test™ works as follows with actionable results within 1 week: Disaggregation of the patient’s tumor tissue and recreation of 3D microtumors that resemble the tumor biology and heterogeneity of the patient’s primary tumor biopsy. Exposure of those 3D microtumors to a panel of potential treatment options. Measuring the metabolic or image-based response of such 3D microtumors, for example as EC50. Results: We created hundreds of 3D micro-tumors from biopsies of 7 ovarian cancer patients. Not surprisingly, when these microtumors were exposed to various cytotoxic chemotherapies such as cisplatin, paclitaxel or gemcitabine or targeted therapies such as erlotinib or crizotinib, the median EC50 varied significantly from drug to drug. However, for any given drug, the EC50 varied significantly from patient to patient, with an interquartile range spreading often by more than one order of magnitude. Values in the table are standardized means with their standard deviations. Conclusions: We have developed a 3D micro-tumor model that can measure the sensitivity of a patient’s cancer biopsy tissue within one week. Furthermore, we found that the sensitivities of those 3D microtumors differed significantly from patient to patient. These results have not yet established a correlation between this 3D micro-tumor model and patients’ tumor responses, which is one of the next steps towards establishing clinical utility for the millions of patients where genomic testing remains non-informative. [Table: see text]
Real time FTIR spectroscopy of tissue smears from gynecologic cancer tissues: A preliminary study.
Authors: Bruchim Ilan , Malonek Dov , Dekel Ben Zion , Reens Carmel Renat , Groisman Gabi , Hallak Mordechai 
Published: May 2019

e17089 Background: Women with suspected Gynecologic cancer undergo surgical procedures during which tissue from suspected areas is excised. Fast histopathology analysis is performed intra-operatively using frozen section (FS) analysis, results of which are available within less than an hour. However, the accuracy of the FS test ranges between 75% and 100% when compared to final histopathology diagnoses. Fourier transform Infrared (FTIR) spectroscopy, utilized for classification of tissue samples into malignant and benign tumors, has shown comparable results to those of FS histopathology analysis. However, the sample preparation time and the effects of tissue preparation on the measured spectra have been a concern for the utilization of this technique in clinical practice. In this study we used attenuated total reflection (ATR) FTIR spectroscopy to examine fresh tissue impression smears as an alternative to the FS technique for rapid classification of tissue samples obtained during surgery. Methods: The study was approved by relevant ethics committees and was conducted in accordance with the Declaration of Helsinki. All patients provided written, informed consent. In total, 23 biopsies (ovarian and uterine) were extracted from suspected tumor sites during surgical procedures and sent to the histopathology laboratory for both pathological and FTIR analyses. Results of the histopathology analysis classified 15 samples as benign and 8 samples as malignant. Prior to the histopathologic analysis, tissue samples from these tumors were lightly pressed against the surface of an ATR crystal, leaving on its' surface impression smears. These smears were air dried for ~5 minutes. Mid-IR absorbance spectra were collected using an ATR-FTIR spectrometer. Machine learning techniques (PCA-LDA and SVM) were utilized to build discrimination models from the absorbance data of the measured smears. Sensitivity and specificity were calculated. Results: IR absorbance spectra of malignant smears were consistently higher from spectra of benign smears in the 850cm-1 to 1450 cm-1 range and they were consistently lower in the 3200cm-1 to 3600cm-1 range. The PCA-LDA discrimination model correctly classified the samples with a sensitivity and specificity of 100%, and the SVM showed a training accuracy of 100% and a cross validation accuracy of 91.3%. Conclusions: These preliminary results suggest that ATR-FTIR spectroscopy of tissue smears may have an important role in the development of next-generation techniques for intra-operative tumor classification.
The role of macrophage production of transforming growth factor-ß in epithelial ovarian cancer progression.
Authors: Roane Brandon , Birrer Michael J. , Goldsberry Whitney , Arend Rebecca Christian 
Published: May 2019

e17100 Background: Increased Transforming Growth Factor- ß (TGF-ß) signaling is associated with poorer prognosis in advanced stage epithelial ovarian carcinoma (EOC). Macrophages are known to produce high amounts of TGF-ß which plays a significant role in immune suppression in the tumor microenvironment Methods: A syngeneic mouse model was created using ID8 cell lines with p53 knocked out. These cells were injected intraperitoneally to establish tumor challenge. One mouse model was treated with TGF-ß monoclonal antibody at the time of tumor inoculation. A second model utilized a mouse line that was engineered to eliminate production of TGF-ß from macrophages specifically. Tumors were harvested and weighed after 42 days of tumor challenge. Flow cytometry was used to analyze differences in CD8 T-cell and T regulatory cell populations. Results: Tumor weights were significantly reduced in mice treated with anti-TGF-ß monoclonal antibody (p = 0.02). Average tumor weights were 125mg vs 101mg comparing non-treated to treated mice. Also, ascites volume was measured using syringe aspiration from peritoneal cavity at the time of sacrifice. Mean ascites volume was 4.7mL vs 2.9 mL (p = 0.004) in untreated mice versus mice treated with monoclonal antibody. In mice with macrophages specific deletion of TGF-ß production, tumors were unable to be established in these mice and omental weights were comparable to tumor naive mice with a mean weight of 34mg compared to 115 mg in wild type mice. In both mouse models there was a significant difference in CD8 : Tregs ratio in omental tumor microenvironment. Conclusions: Increased amounts of TGF-ß contribute to increased tumor invasion and migration, while loss of TGF-ß results in both a decrease in tumor burden and a decrease in suppressors of T cell activity. Inhibition of TGF-ß, demonstrated with a monoclonal antibody can effectively reduce TGF-β signaling. The macrophages within the omental tumor microenvironment are a source of large amounts of TGF-ß and when lost result in an inability to establish tumors in intraperitoneal tumors.
Comparison of preoperative serum VEGF in leiomyosarcoma and uterus myomatosus patients: A proof of concept study.
Authors: De Gregorio Amelie , Bekes Inga , de Gregorio Nikolaus , Andres Sophia , Hoffmeister Diego , Swerev Tatjana , Friedl Thomas W. P. , Janni Wolfgang , Ebner Florian 
Published: May 2019

e17117 Background: The preoperative differentiation of a uterine fibroid from a sarcoma is still a pending clinical problem. Currently with the suspicion of a sarcoma (LMS) the more invasive open surgical approach is recommended to minimise the risk of LMS fragmentation and distribution. In a minority of cases, a malignancy is indicated by clinical suspicion, pre-surgical imaging or routine serum blood samples (SBS). Our hypothesis postulates higher VEGF levels in LMS compared to fibroid patients in the pre-surgical SBS. To assess this hypothesis, SBS were taken from patients with the clinical suspicion of LMS after informed consent and analysed after histology confirmed the diagnosis. Methods: Case series of patients with suspected LMS over a 4year time period. Analysis was performed via SBS collected from LMS- and fibroid patients before surgery. Serum VEGF protein was measured by ELISA. The final tumor histology was obtained from the report of the institutional pathologist. VEGF-serum levels were then compared between fibroid and LMS patients using the non-parametric Mann-Whitney U test. Results: 25 patient SBS were collected prior to surgery. In 9 cases the histopathology confirmed a LMS, with heterogeneous pTNM classifications. On average, VEGF serum levels were higher in the LMS patients as compared to the fibroid patients (628,96 pg/ml vs 351,91 pg/ml; further statistics see Table 1); however, the difference was not statistically significant (Mann-Whitney-U Test, p = 0.141). Conclusions: This proof-of-concept study with a small sample size of pre-surgical SBS indicates that VEGF serum levels may be increased in patients with histologically confirmed LMS; however, larger sample sizes are needed to validate our findings. If additional studies confirm a pronounced increase in pre-surgical serum VEGF levels in LMS patients, serum VEGF levels might routinely be used to assess the risk for a LMS in patients presenting with clinical uterine fibroids. [Table: see text]
Mutational landscape of endometrial cancer identified by prospective clinical sequencing in a nationwide cancer network.
Authors: Schink Julian C. , Alvarez Ricardo H. , Elvin Julia Andrea , Moran Amber , Rollins Rebecca , Geisler John P. , McIntosh David , Godbee Natalie , Tan Bradford A. , Markman Maurie 
Published: May 2019

e17123 Background: Tumor genomic profiling is a critical component of precision oncology allowing the detection of genomic alterations (GA) that have the potential to be targeted therapeutically. We present an analysis of comprehensive genomic profiling (CGP) of a large series of endometrial cancer (EC) patients assayed in a nationwide cancer network. Methods: 278 Pts with advanced EC underwent CGP with hybrid capture of up to 406 cancer-related genes on tumor tissue or for 62 genes on circulating tumor DNA ordered during clinical care for treatment decision-making between 01-2013 to 05-2018. Clinically relevant genomic alterations (CRGA) were defined as associated with targeted therapies or mechanism-driven clinical trials. The treatment histories for these patients were obtained with IRB-approved retrospective review. Results: Median age was 59 years (range, 37-85), 58% were Caucasian. GA were identified in 97% (271/278) of EC, of which 218 (80%) had a clinically relevant genomic alteration (CRGA). PI3K/AKT/mTOR pathway ( PIK3CA, AKT1/2/3, PIK3R1, PTEN, MTOR, STK11, FBXW7) CRGA were most common, present in 63.8% of EC. CRGA in other targetable pathways were identified: 28.4% in MEK ( KRAS, NRAS, HRAS, BRAF, RAF1, GNAS, NF1, NF2) , 12.5% in HRD (BRCA1/2, ATM, PALB2, BRIP1 ) and 9.9% in ERBB ( ERBB2, ERBB3, ERBB4, EGFR). 26 patients are MSI-high 9.5% (26/271) and 21 patients are TMB-high 7.7% (21/271). 29.8% (65/218) of EC patients were ordered a genomically-matched treatment, and 61 of these patients received the treatment. 69.2% (45/65) were agents that were FDA approved in a different tumor type, and 24.6% (16/65) through referral to a matched mechanism driven clinical trial. With access to the clinical trial TAPUR, the frequency of matched treatment through clinical trials increased over time from 2013 to 2018. The median PFS for non-clinical trial study patients was 9 weeks, and the median OS was 27 weeks. Conclusions: In a large series of Endometrial and Uterine cancer patients assayed with CGP, 27.9% (61/218) of pts received matched treatment, which was predominantly targeted therapy. The comprehensive sensitive and unbiased nature of CGP, coupled with a multidisciplinary molecular tumor board and staff dedicated to genomic interpretation, assisted in achieving a high frequency of patients’ participation in clinical trials and gene-directed treatment.
The incidence of microscopic adnexal metastatic disease in women with presumed early stage endometrial cancer.
Authors: Khadraoui Wafa , Tierney Christina , Chung Sophie , Azodi Masoud , Ratner Elena , Menderes Gulden 
Published: May 2019

e17128 Background: The standard surgical staging for endometrial cancer has been established as a total laparoscopic hysterectomy,bilateral salpingo-oopherectomy and lymphadenectomies. However, ovarian removal can have significant consequences in pre- and peri-menopausal women, which comprise 25% newly diagnosed endometrial cancer. The potential ramifications of premature surgical menopause are clinically important. The goal of this study is to determine the incidence of microscopic adnexal metastatic disease in younger patients with presumed early stage endometrial cancer. Methods: From January 2005 through December 2010, 57 women who were 52 years old or younger with presumed early stage endometrial cancer were identified from our institutional database. Inclusion criteria included (1) FIGO grade 1 endometrioid endometrial cancer on endometrial biopsy, or (2) FIGO grade 1 endometrioid endometrial cancer on frozen section specimen with < 50% myometrial invasion, no evidence of metastatic disease on pre-operative imaging, and no grossly visible metastatic disease in the peritoneal cavity during the staging surgery. Results: Of these 57 patients, four (7%) had lymphovascular space invasion, 20 (35%) had lower uterine segment involvement, 26 (45%) had superficial myometrial invasion or no residual carcinoma, while three (5%) unexpectedly had 50% or greater myometrial invasion on final pathology. Half of our patient population (50%) received vaginal brachytherapy. Of the 57 patients, one (1.8%) had microscopic adnexal involvement in a fallopian tube which upstaged her to stage IIIA disease. Pathological risk factors for advanced stage included LVI, lower uterine segment disease, and 50% myometrial invasion. Conclusions: After a thorough pre-operative evaluation and intra-operative exploration, preservation of the ovaries appears to be a safe and viable option for younger women who are diagnosed with presumed early stage disease. We suggest that ovarian preservation should be discussed on an individual basis in pre- peri-menopausal patients who meet the above-mentioned strict eligibility criteria.
Non-opioid analgesics: New opportunities in early rehabilitation of patients with gynecological cancer.
Authors: Tumanyan Sergey V. , Kit Oleg I. , Frantsiyants Elena M. , Moiseenko Tatiana I. , Oros Oksana V. , Sugak Elizaveta Yu. 
Published: May 2019

e17129 Background: An important principle of analgesia is its effect on each component of the pain formation. The purpose of the study was to improve analgesia in the perioperative period in patients with gynecological cancer. Methods: This prospective randomized study of the quality and effectiveness of various analgesics included 97 patients aged 22-67 years receiving surgery for gynecological cancer. The patients were divided into two groups. Group 1 (n = 47): patient-controlled analgesia with trimeperidine and nonsteroidal anti-inflammatory drugs (NSAIDs); group 2 (n = 50): preemptive analgesia based on lidocaine, magnesium sulphate, nefopam and NSAIDs. Results and pain syndrome were assessed by levels of glucose, cortisol, insulin, lactate, C-reactive protein (CRP), Kerdo autonomic index, visual analogue scale (VAS), levels of personal and reactive anxiety and depression. Results: Analgesic effect of trimeperidine was obtained in 83.3% (p < 0.05). However, the effect was less pronounced, compared to non-opioid analgesics, and did not reduce the psychosomatic component of pain after surgical treatment. In group 2, non-opioid analgesia limited the increase of cortisol, glucose, insulin, CRP and lactate (p < 0.05) providing effective pain relief in the perioperative period. Non-opioid analgesics promoted an optimal analgesic effect, did not cause residual sedation, anxiety, depressive effects and cognitive impairments, which showed their obvious advantage over opioids. Opioid-sparing effect was 96.3% (p < 0.05). Reducing the consumption of narcotic analgesics without worsening the quality of postoperative analgesia and the patient's well-being is an important advantage which allows minimizing the negative effects of opioids, facilitating the early rehabilitation of patients. Conclusions: Non-opioid analgesics can significantly limit endocrine and metabolic changes without worsening the quality of analgesia in the perioperative period.
Which role plays specialized palliative care in patients with relapsed and/or metastatic head and neck cancer? A retrospective analysis in Southern Switzerland.
Authors: Espeli Vittoria G. , Gamondi Claudia , Fusi-Schmidhauser Tanja 
Published: May 2019

e17503 Background: early palliative care (PC) for patients with advanced cancer improves quality of life, promotes home deaths and can improve survival. Limited data are available regarding PC in advanced head and neck cancer (HNC) patients. To investigate the effect of introducing specialized PC in patients with relapsed and/or metastatic head and neck cancer. Methods: between October 2010 and December 2018, the medical charts of all patients treated in the Oncology Institute of Southern Switzerland with relapsed and/or metastatic HNC were reviewed. Site, status of disease (metastatic at diagnosis, locally or metastatic relapsed), type and lines of treatment, treatment response and referral to specialist palliative care (yes or no) were documented. Comparisons were made between patients referred and non-referred to PC. Results: sixty-two patients with relapsed/metastatic HNC were identified, 32 (51.6%) of which were referred to specialized PC. Patients were mainly men (47, 75.8%), with a median age of 66 years (range 43 – 86). Forty-two patients (67.7%) had a metastatic disease and the most common site of tumor was the oropharynx (35.5%), followed by oral cavity (32.3%), larynx (16.1%), hypopharynx (12.9%), and unknown primary (3.2%). Forty-eight patients (77.4%) were treated with systemic treatment (75% in the PC group and 80% in the non-PC group, p = 0.638). The median overall survival was 8.1 months for all patients, 8 months for the PC group and 8.7 months for the non-PC group, without significant difference (p = 0.440). Of the deceased patients, 70% of the PC group and 73.3% of the non-PC group received chemotherapy in the last three months of life. A greater percentage of patients in the PC group died at home, but without significant difference (39.2% vs. 19%, p = 0.134). Conclusions: only half of the patient had access to specialized PC. Whereas it did not seem to affect overall survival nor influence chemotherapy prescription, it seemed to favor home deaths. Further studies investigating the impact of early PC in recurrent and/or metastatic HNC are needed to improve access to PC and maximize benefits.