bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preclinical studies of SB 11285, a novel STING agonist for immuno-oncology.
Authors: Challa Sreerupa Valli , Zhou Shenghua , Sheri Anjaneyulu , Padmanabhan Seetharamaiyer , Meher Geeta , Gimi Rayomand , Schmidt Diane , Cleary Dillon , Afdhal Nezam , Iyer Radhakrishnan 
Published: September 2018

e14616 Background: The activation of innate and adaptive immunity via Stimulator of Interferon Genes (STING) signaling is a potentially transformative immuno-therapeutic strategy in cancer. We report here in vivo efficacy and safety studies of SB 11285. Methods: Tumor Growth Inhibition (TGI) and Tumor Growth Delay (TGD) studies in syngeneic mouse models were initiated when mean tumor volume (MTV) reached 100mm3: A20 Lymphoma: (10 animals/Group); (A) Saline; (B) 100µg SB 11285, intratumoral (i.t.), days 3,4,6,8,10; (C) 100mg/kg Cyclophosphamide, intraperitoneal (i.p), days 1,2; and (D) combination of cyclophosphamide+SB 11285. CT26 Colon Carcinoma experimental design is shown in Table. Re-challenge study was initiated in tumor-free animals in A20 lymphoma model on day 73, and monitored for an additional 45 days. Presence of activated immune cells intumor tissues was evaluated by immuno-histochemistry. Cytokine response was evaluated in serum after a single i.p. injection of SB 11285 at 10mg/kg. Maximum Tolerated Dose (MTD) in mice was determined by daily i.p. injection of SB 11285 for 10 days. Results: A20 model: % TGI in the treatment groups were—A, 0; B, 86; C, 98, and D, 93; % TGD, day 70: A, 0; B, 64; C, 156; D, 288. In D, day 73, 90% of animals remained tumor-free. CT26 model: Table 1 shows MTV on day 19 and %TGD on day 43; Re-challenge study. All animals from the SB 11285-treated groups remained completely tumor-free on day 45 compared to control group (MTV,1666 mm3); Immuno-histochemistry of SB 11285-treated groups, revealed the infiltration of CD8+T and NK cells into tumor and surrounding tissues; Cytokine analysis did not show systemic inflammatory response; MTD of SB 11285 was 16 mg/kg/day. Conclusions: SB 11285, a novel STING agonist, showed very potent, and highly durable immune response-mediated anti-tumor activity. SB 11285 was well tolerated, safe, and is being advanced to IND-enabling studies. [Table: see text]
Programmed death (PD)-ligand 1 (L1) expression and mismatch repair (MMR) deficiency across tumor types: Candidates for checkpoint inhibitor based immunotherapy.
Authors: Kim Seung Tae , Park Se Hoon , Park Joon Oh , Park Young Suk , Lim Ho Yeong , Kang Won Ki , Lee Su Jin , Kim Kyoung-Mee , Lee Jeeyun 
Published: September 2018

e14622 Background: The identification of biomarkers associated with response to therapeutic agents has changed the paradigm of cancer treatment into the precision medicine by identification of right targets across cancer types. PD-L1 expression and mutational or neoatigen burden (Mismatch repair (MMR) deficiency) have been actively studied as the predictive biomarkers for the response to immune checkpoint inhibitors. Methods: We have conducted the PD-L1 and hMLH1/MSH2 expression (MMR deficiency) as part of a clinical practice for 430 patients with advanced gastrointestinal (GI) cancer, genitourinary (GU) cancer or rare cancers between June 2012 and March 2016. Herein, we evaluated potential candidates who could be targeted to further immune checkpoint inhibitors. Results: In 430 patients, 414 (96.2%) patients were available to evaluate the status of PD-L1 expression by immunohistochemistry (IHC). Irrespective of tumor-types, overall 26.8% (111 of 414) exhibited expression of PD-L1 in tumor tissues. The PD-L1 expression was examined as follows; 33.5% in HCC, 31.0% in CRC, 27.3% in GC, 25.5% in melanoma, 18.8% in BTC, 16.7% in pancreatic cancer, 15.8% in sarcoma and 13.0% in GU cancer. Among the 394 patients available for MLH1/MSH2 expression, only 18 patients (4.5%) had the MMR-deficient tumors with complete loss of MLH1/MSH2 expression. The MMR-deficiency was observed as follows; 7.9% in GC, 6.7% in HCC, 4.0% in CRC, and 2.7% in sarcoma. On 382 patients evaluable for the status of both PD-L1 and MLH1/MSH2 expression, there was no the significant association between the PD-L1 expression and MLH1/MSH2 loss (p = 0.267) Conclusions: These data may provide useful information and background for future research for immune checkpoint inhibitor across tumor-types. As a single selection biomarker for immune checkpoint inhibitor in various tumor-types, neither the PD-L1 expression nor the MMR deficiency is optimal application in clinical trials.
The antiviral effect of poly-gamma-glutamic acid (γ-PGA) in HPV-positive patients.
Authors: Lee Jae Kwan , Cho Hyun Woong , Kim Seunghoon , Park Min Young , Sung Moon Hee 
Published: September 2018

e14623 Background: Poly-gamma-glutamic acid (γ-PGA), as a signaling regulator of Toll-like receptor 4 (TLR4), has been shown to induce innate immune responses. In previous non-clinical study, we showed that γ-PGA induces signaling pathway of Type 1 interferon, which consequently eliminates various viruses such as SARS, hepatitis C virus, influenza virus, etc. To evaluate the clinical efficacy of γ-PGA, we’ve investigated the antiviral effect of γ-PGA on human. In retrospective study to evaluate, the clinical significance of g-PGA treatment for vaginal intraepithelial neoplasia (VAIN), γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive VAIN. Since previous human studies showed the possibility of a drug, we have completed a phase I dose escalation study to determine the safety, tolerance and pharmacokinetics of γ-PGA in healthy adult male subjects. Methods: In the current study, we designed a human study of γ-PGA orally treated daily (75 mL) for 24 weeks to demonstrate the antiviral effect of γ-PGA in female HPV-positive patients. HPV viral load and cell-mediated immune responses were measured during 24 weeks to compare HPV clearance rates between the γ-PGA-treated group and the placebo-controlled group and to evaluate immunological parameters, respectively. Results: . In phase IIb clinical trial to evaluate the efficacy and safety of γ-PGA for the fertile women with cervical intraepithelial neoplasia grade 1 (CIN1) patients, regression rate by the treatment of γ-PGA was 45.65%, whereas the placebo controls were 30.23% in ITT group with statistically significance ( p= 0.0247). Conclusions: γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive CIN I.
Safety of intraoperative chemotherapy with 5-FU for colorectal cancer patients receiving curative resection: A randomized, multicenter, prospective, phase III IOCCRC trial (IOCCRC).
Authors: Zhang Rong-xin , Lin Jun-zhong , Chen Gong , LI Li-ren , LU Zhen-hai , Ding Pei-Rong , Wu Xiao Jun , Wan Desen , Pan Zhi-zhong 
Published: September 2018

e15002 Background: The safety and efficacy of intraoperative chemotherapy in colorectal cancer have not yet been extensively investigated. This randomized control trial was designed to compare the safety and efficacy of intraoperative chemotherapy in combination with surgical resection to those of traditional surgical resection alone. Patients and Methods: From January 2011 to January 2016, 696 colorectal cancer patients were enrolled in this study: 341 patients were randomly assigned to the intraoperative plus surgery group to receive intraoperative chemotherapy (portal vein, intraluminal, and intraperitoneal chemotherapy plus surgical resection), whereas 344 patients were randomized to the control group to undergo surgery alone. Eleven patients withdrew consent. Surgical complications and side effects of intraoperative chemotherapy were compared between the two groups. Results: Intraoperative chemotherapy did not increase the rate of surgical complications, and no severe chemotherapy-associated side effects were observed. There were no significant differences in the length of hospital stay (8.31 vs. 7.98 days, P = 0.138), length of surgery (170.4 vs. 167.0 min, P = 0.526), length of antibiotic use (2.28 vs. 2.15 days, P = 0.322), or length of drain usage (6.37 vs. 6.16 days, P = 0.387) between the intraoperative chemotherapy and control groups. Four patients in each of the intraoperative chemotherapy and the control groups experienced anastomotic leakage and underwent a second operation (1.2% vs. 1.2%, P = 0.99). There were no deaths within 90 days after surgery in the chemotherapy group, whereas one patient died in the control group (0% vs. 0.3%, P = 0.99). Intraoperative chemotherapy did not decrease the rate of patients who received postoperative adjuvant chemotherapy between the intraoperative group and control group (29.3% vs. 30.2%, P = 0.795). Conclusions: Intraoperative chemotherapy can be safely performed during colorectal surgery; however, follow-up is necessary for a better assessment of its efficacy. Register Number: NCT01465451. Clinical trial information: NCT01465451.
A pilot study of Irinotecan plus raltitrexed as second-line treatment for advanced colorectal cancer.
Authors: Qu Xiujuan , Wu Zhenhai , Wang Shuo , Qu Jinglei , Zhang Lingyun , Liu Jing , Shi Jing , Zhang Jingdong , Liu Yunpeng 
Published: September 2018

e15024 Background: This pilot study is aimed to evaluated the efficacy and safety of irinotecan plus raltitrexed as second-line treatment for advanced colorectal cancer patients. Methods: A pilot study was made among patients with advanced, previously treated colorectal cancer from June 2013 to April 2016 in the First Hospital, China Medical University,. A total of 13 patients eligible were enrolled to receive irinotecan at a dose of 180mg/m2 d1, plus raltitrexed at a dose of 3mg/m2 d1, every 3 weeks, until disease progression or un-tolerable adverse events. All statistical analyses were performed using the SPSS (21.0) software program. Kaplan–Meier analysis and Log-rank test were used for survival analysis. P < 0.05 was considered as statistically significant. The primary end point was time to progression (TTP) and objective response rate (ORR), the secondary end point was safety. Results:The median follow-up time was 10.1 months at data cut-off on Dec1, 2016. 11 patients were defined progression of disease (PD) based on the criteria of RECIST 1.1 and 6 patients died. The median TTP of second-line was 4.0 months. The rate of disease control rate (DCR) was 46.2% (6patients stable disease). In univariate analysis, sex (3.2months of 12male patients versus 4.6months of 1female patient, P = 0.926), body mass index (BMI) (3.2months of 5 patients BMI < = 24 versus 4.0months of 8 patients BMI > 24, P = 0.311), site of tumor (4.0months of left versus 3.2months of right, P = 0.555) were not associated with TTP. Safety was assessed within 10 patients including nausea (70%), vomiting (30%), diarrhea (60%), constipation (10%), fatigue (90%), fever (20%), hand foot syndrome (20%), rash (40%), alopecia (40%), palpitations (20%), oral mucositis (10%), neurotoxicity (50%). 2 of 9 patients (22.2%) had hematologic toxic. Liver injury occurred in 3 of 8 patients (37.5%) and no kidney injury was reported. Conclusions: In advanced colorectal cancer patients, irinotecan plus raltitrexed as second-line treatment showed encouraging clinical activity and a tolerable safety profile.
Treatment monitoring of metastatic colorectal cancer by quantification and genotyping of mutated KRAS in circulating cell-free DNA.
Authors: Seufferlein Thomas , Schwerdel Daniel , Welz Hanna , Marienfeld Ralf , Schmidt Stefan A. , Kleger Alexander , Ettrich Thomas Jens , Berger Andreas W. 
Published: September 2018

e15037 Background: Treatment of stage IV colorectal cancer (mCRC) has made substantial progress over the last years but therapy monitoring still is in its early stage. A facile, non-invasive, repeatable assessment of the mutational state of a given tumor even during treatment could constitute a desirable biomarker for therapy stratification and disease monitoring. "Liquid biopsies" analyzing circulating free and circulating tumor DNA (cfDNA/ctDNA) from patients’ blood have been proposed as a a simple, non-invasive method that could fulfil this requirement. Methods: 27 patients with histologically confirmed mCRC were enrolled into a treatment surveillance cohort. For the analysis of concordance between tumor tissue DNA and cfDNA we analyzed 40 tissue and blood pairs from therapy naïve patients regarding their KRAS mutation status. The course of cfDNA values combined with targeted genotyping of KRAS mutations were assessed during several palliative chemotherapeutic regimens. cfDNA data were correlated with clinical parameters to establish its prognostic and predictive value. Results: Baseline cfDNA levels allow to significantly differentiate mCRC from healthy controls (14.23 ± 6.33 ng/ml vs. 2.60 ± 1.59 ng/ml; p < 0.0001). cfDNA values at baseline in therapy naïve patients correlate well with tumor burden (p < 0.05) and CEA levels (p < 0.05). cfDNA values significantly increased upon disease progression during 1st (p < 0.01) and 2nd line (p < 0.05) treatment, enabling a non-invasive disease monitoring approach. Moreover, there was a significant correlation between the cfDNA levels upon treatment and progression-free survival (p < 0.05). In addition, our data show that KRAS genotyping of cfDNA under therapy is feasible (80% blood-tissue concordance) and might benefit the patient due to early detection of therapy resistance. Conclusions: Repetitive quantitative and mutational analysis of cfDNA is likely to complement current diagnostic standards in stage IV CRC over the whole continuum of treatment.
18F-FDG PET/CT evaluation of tumor response to the implantation of RENCA macrobeads (RMB) in phase I and II clinical trials [INDBB 10091] in advanced, treatment-resistant metastatic colorectal cancer (mCRC).
Authors: Nazarian Angelica , Sureshbabu Sudipta , Andrada Zoe Padua , Thomas Joanne , Arreglado Anna , Berman Nathaniel , Wolf David J. , Gazda Lawrence S. , Fahey Thomas J. , Ocean Allyson J. , Smith Barry H. 
Published: September 2018

e15046 Background: RMB, a cytostatic, biological system form of anti cancer therapy have been used in Ph I & II clinical trials in mCRC w/ evidence of improved survival benefit & QOL. Evaluation of metastatic tumor response by standard CT RECIST criteria however has been unsatisfactory. We hypothesized that using 18F FDG PET/CT scan to evaluate tumor anatomy & metabolism could provide a more accurate picture of tumor response to RMB Methods: 48 mCRC pts (14, Ph 1; 34, Ph 2a) who failed available treatments were implanted intraperitoneally w/ RMB (8mb/kg). Physicals, biomarkers & lab evaluation were obtained at baseline & days 14-90, with PET CT imaging at baseline & day 90. PET scan was acquired 1 hour after FDG injection of 9.4 mCi. CT was used for attenuation correction. Correlation between 18F FDG PET SUVmax findings & CEA & or CA19-9 responses was assessed. Positive response was defined as ≥20% decrease post implant in CEA, CA19-9 & SUV. Only tumors w/ SUVmax ≥ 2.5 were evaluated. SUV measurements were made by 1 radiologist experienced in PET-CT scanning & SUV determination Results: 123 FDG positive mCRC lesions (39, Ph 1; 84 Ph 2a) were detected in 37 evaluable pts (14 m, 23 f; mean age 58.2; SUVmax 2.5-17.5). Of the 37 pts, 28 (76%) showed stabilization & or decreased FDG uptake (4 w/ frank necrosis) as well as stable/decreased CT tumor measurements. Pts w/ pulmonary lesions showed greater responses than those w/ hepatic lesions. 9 (24%) of 37 pts showed increased SUVs. 23 pts (62%) showed decrease in CEA & or CA 19-9 ≥ 20%. 17 pts (74%; 13 decrease, 4 central & peripheral necrosis) had correlation between decreased SUVs/necrosis & biomarkers decrease Conclusions: We conclude SUVs are useful in monitoring mCRC lesions response to RMB therapy. Changes in SUVs correlate w/ CEA & CA 19-9 changes. Taken together the combined data indicate anti tumor effect in these Ph 1/2a trials & offer preliminary support for our hypothesis that 18FDG can be useful in evaluating cell system therapies. Issues of SUVmax standardization & effects of intra tumor heterogeneity however must be considered. Further studies are merited & ongoing, including a planned Ph 3 trial Clinical trial information: NCT01053013; NCT00283075.
Chemotherapy efficacy in metastatic colorectal cancer (mCRC) patients treated with adjuvant or first-line FOLFOX-based chemotherapy.
Authors: Samalin Emmanuelle , Nguyen Tien Tuan , Thezenas Simon , Portales Fabienne , Mazard Thibault , Gourgou Sophie , Assenat Eric , Ychou Marc 
Published: September 2018

e15048 Background: Efficacy results of Folfox or Folfiri chemotherapies (CT) are not different as 1st line in mCRC patients, alone or with targeted therapies. No data reported on progression-free survival (PFS) of 1st line Folfiri after Folfox-based adjuvant CT and of 2nd line Folfiri-based CT after a Folfox-based 1st line. The objective was to evaluate the efficacy of a Folfiri-based CT after adjuvant or 1stline Folfox-based treatment. Methods: 210 of 568 pts from a mCRC database were retrospectively selected and divided in 2 cohorts: pts who received adjuvant Folfox then Folfiri as 1st line treatment (n = 76, AdjF) and those treated with Folfox as 1st line treatment then Folfiri 2nd line (n = 134, FFox). PFS1 was the time from beginning of Folfox to 1st progression and PFS2 the time from the Irinotecan-based CT to 2ndprogression. Results: Median age was 62 (22-80). 49.3% pts had synchronous liver (72%) metastases. Primary tumour was right and left colon in 22% and 70% patients. Primary tumour was resected in 91% pts (98.7% and 86.6% in the AdjF and FFox groups, p= 0.003). KRASand BRAF-mutated status were found in 21.8% and 4.7% pts. In the AdjF group, pts received Folfiri as 1st line combined with Bevacizumab (Beva) or anti-EGFR therapy (Cetuximab or Panitumumab) in 70% and 13% cases. In the FFox group, 1st line Folfox-based CT was associated with Beva and anti-EGFRs in 7 and 6% pts, and 2ndline Folfiri-based CT with Beva or Aflibercept in 51 and 4% pts, and with anti-EGFRs in 7.5%. Median duration of a therapeutic line was 5 months (0-29.8). Grade 3-4 toxicities were for the AdjF and FFox groups respectively, diarrhea 13/15%, neutropenia (febrile) 16(7)/37%(1%) and neuropathy 24/18%. Response rates were 55.3% and 68.7% in the AdjF and FFox groups. Median PFS1 were 14 (95%CI:10-16) and 10 (95%CI:8-11) months in the AdjF and FFox groups, and PFS2 10 (95%CI:8-11) and 7 (95%CI:6-9) months, respectively. Median overall survival was 43 (95%CI:39-50) and 33 months (95%CI:26-36) respectively. Conclusions: Results in terms of survival are in favor of the AdjFFox group. It would be interesting to identify a subgroup of pts rapidly progressing after adjuvant Folfox, who might show the same profile than pts in the FFox group.
Sidedness and prognostic factors of peritoneal metastatic colorectal cancer: A single center experience.
Authors: Ilhan Aysegul , Demirci Umut , Aksel Bulent , Aslan Ferit , Dogan Lutfi , Oksuzoglu Berna 
Published: September 2018

e15050 Background: Peritoneal metastasis in colorectal cancer (pCRC) is associated with poor prognosis. This study aimed to present a single centre experience for patients with pCRC. Methods: Between 2012 and 2016, 60 patients diagnosed with pCRC included in this study. Demographic and clinico-pathologic characterictics of patients were retrospectively analysed using patient medical records. Results: A total of 60 patients (31 female) were included and the median age was 61. Fifty-five patients (91%) had peritoneal metastases at the initial diagnosis, 37 patients (61%) had the left-sided colon cancer and 33 patients (55%) had the visceral metastases. Peritoneal metastasis was detected in 7 patients during the primary surgery. 30 patients (50%) received biologic therapy; 25 patients (41.6%) received anti-VEGF (bev) and 5 patients (8.3%) received anti-EGFR (cet/ pan) as the first line therapy. Seven (11%) patients underwent cytoreductive surgery and HIPEC. Median PFS of the analyzed patients was 10 months (SE: 2; 95% CI 6-13.9) and mOS was 20 months (SE: 4.2; 95% CI 11.7-28.7). The mPFS and mOS were 16.6 months (SE: 4.9; 95% CI 6.9-26.4) and 28 months (SE:7.1; 95% CI 13.8-42.1) in the group received surgery and HIPEC, respectively. No statistically significant survival difference was detected in terms of primary tumor localization, the presence of visceral metastasis (Table 1). Conclusions: In our study, the prognosis of pCRC patients was observed to be worse regardless of localization and the presence of accompanying visceral disease. A statistically significant difference was observed in the survival of the patients that received biologics. [Table: see text]
The risk of malnutrition in patients with a colon carcinoma: An analysis of 13239 patients.
Authors: Meissner Carl , Fahlke Joerg , Otto Ronny , Kahl Christoph , Krueger Matthias , Asperger Walter , Ptok Henry , Lippert Hans , Ridwelski Karsten 
Published: September 2018

e15057 Background: The problem of under-nutrition and lack of nutrition is increasingly placed in the focus of operational discipline. Many of them are deficient in malnutrition before being hospitalized. In surgical therapy, the prevention of postoperative complications is of utmost importance. Due to a preoperative condition of malnutrition, the complication rate may increase and thus the associated increased treatment therapy costs per patient. The consequence, of course, is also a diminished postoperative treatment quality of the treating clinic. Methods: Prospective Multicentric Observational Study: "Quality Assurance Study Colorectal Cancer from 2010-2014 of the" An Institute for Quality Assurance in Operational Medicine "at the Otto-von-Guericke-University Magdeburg. The screening for lack of nutrition was carried out with the Nutritional Risk Screening (NRS 2002) Kondrup J et al .. Results: 13239 primary data records from 2010 to 2014 were included. With the help of the NRS screening, a total score in the form of a scoring system is possible. The sum of 3 points or more identifies a patient with a nutrition-related risk and should be a cause for further diagnosis and therapy. The median of all colorectal cancer patients was NRS = 3. 65.4% of the patients had an NRS score of > = 3. In morbidity, the complications in colorectal cancer patients with NRS > = 3 points are significantly increased. Also in the case of general complications (such as pneumonia, urinary tract infection, etc.) the rate increases with a larger NRS score. Conclusions: If the risk of malnutrition is small in patients with a colon carcinoma, the morbidity is low.