bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of tolerability and reactions of immune checkpoint inhibitors.
Authors: Sever Ozlem Nuray , Sonmez Ozlem , Demir Osman Gokhan 
Published: September 2018

e14605 Background: Immunotherapies have revolutionized the treatment of cancer, especially in recent years. Today, there are anti-CTLA-4 antibodies and PD-L1 monoclonal antibodies which are active in use as checkpoint inhibitors. Side effects of these agents have a different spectrum in the form of immuno-related side effects. Methods: In this study, we aimed to evaluate the side effect and tolerability in patients treated with immune checkpoint inhibitors in our clinic. Results: 32 patients who were treated with PD-L1 monoclonal antibodies between August 2015 and January 2017 were screened retrospectively in our clinic. Six of the cases had immuno-related side effects (18.75%). 2 patients had a elevated liver function test. Both patients were diagnosed with NSCLC. In both of them, elevation was detected in the second course of nivolumab treatment, and the USG and hepatitis markers of the patients were normal. Enzymes returned to normal after treatment interruption. In a patient diagnosed with malignant melanoma that receiving pembrolizumab colitis was developed after 3th cycles of the therapy. The treatment of the patient who recovered after steroid administration and treatment interruption continued until the 8th cure. In the third cure of the patient with NSCLC, when nivolumab was used pneumonitis was diagnosed. Steroid treatment was applied for 2 weeks. Our patient continued to use nivolumab for up to 22 cycles. In our patient with malign melanoma that treated with pembrolizumab autoimmune thyroiditis developed. We started prednisolone treatment. After recovery our patient's treatment continued. In one of our patient who was diagnosed with malign melanoma, after the second cure of the treatment, diffuse edema and shortness of breath due to heart failure was detected. Echocardiography revealed a low ejection fraction. Methylprednisolone was started by cessation of treatment. Control ejection fractions normalized. Conclusions: İmmuno-related side effects were regarded as manageable side effects and no treatment change was needed. Immune Checkpoint inhibitors, which have been shown to be useful for survival every day, are proceeding to take a favorable position in the treatment of cancer with ease of use and lack of side effects.
Safety and efficacy of concurrent administration of influenza vaccine in patients undergoing anti-PD-1 immunotherapy.
Authors: Kanaloupitis Dimitra Konstantinos , Chandran Anjana , Ralph Alyssa , Thompson Ryan , Richards Jon M. , Hallmeyer Sigrun 
Published: September 2018

e14607 Background: Concerns have been raised over administration of influenza vaccination concurrent with immune checkpoint inhibitor therapy, specifically, implication in induction of Guillain-Barre syndrome. The aim of this study is to assess the safety and efficacy of influenza vaccination in patients undergoing anti-PD1 therapy. Methods: This is a prospective observational study evaluating the safety and efficacy of Afluria (Seqirus) in patients receiving anti-PD1 therapy. Antibody titers against common influenza A and B antigens were measured by a semi-quantitative ELISA on days 0, 45 and 90+ post vaccine administration to confirm anti-PD1 therapy did not interfere with anti-influenza humoral responses. Influenza infection, confirmed by rapid antigen testing, and influenza-related hospitalizations were reported among vaccinated patients. Safety was assessed using the FDA toxicity grading scale for clinical trials. Results: The acute humoral responses and subsequent IgG responses of the 28 patients included in this study are as follows in the table. IgM responses at 45 days to both influenza A and B common antigens were statistically significant (all P<0.05*). IgG response to common influenza B antigens was increased at day 45 ( P=0.001*). One of 28 patients contracted influenza B infection, confirmed by rapid antigen testing. There were no influenza-related hospitalizations. One patient had a grade 2 local adverse event (AE). A second patient had both a grade 2 local and a grade 2 systemic AE (myalgia). No grade 3/4 local or systemic AEs were reported. Conclusions: Administration of influenza vaccination concurrent with anti-PD1 therapy appeared safe in our study. No grade 3/4 local or systemic AEs were noted. Anti-PD1 therapy did not adversely affect anti-influenza humoral responses. Our data demonstrate that the increase in IgM reactivity to common influenza A and B antigens appears to be an immediate reaction to revaccination. Seroprotection can be inferred by documented infection in only one patient and absence of influenza related-hospitalizations. [Table: see text]
Specific adaptive immune pattern induced by NBTXR3 exposed to radiation therapy in soft tissue sarcoma (STS) patients.
Authors: Galon Jerome , Laé Marick , Papai Zsuzsanna , Rochaix Philippe , Mangel Laszlo Csaba , Mlecnik Bernhard , Hermitte Fabienne , Sapi Zoltan , Delannes Martine , Tornoczky Tamas , Vincent-Salomon Anne , Bonvalot Sylvie 
Published: September 2018

e14615 Background: NBTXR3 are functionalized hafnium oxide nanoparticles, undergoing seven clinical trials for enhancing radiation therapy (RT). The high electron density of the nanoparticles, when exposed to radiotherapy (NBTXR3 + RT), allow absorption/deposition of a high radiation dose within the cancer cells to physically kill the cells, and possibly improve outcome. Besides, NBTXR3 + RT has shown subsequent ability to enhance immunogenic cell death and immune response in preclinics. We hypothesized that NBTXR3 + RT could trigger an enhanced immune response when compared to RT in patients with STS. Methods: Tumor tissues pre- (biopsy) and/or post-treatment (resection) were collected from patients (pts) with locally advanced STS, who received either NBTXR3 as intratumor injection and RT (14 pts) or RT (12 pts), as preoperative treatment (NCT02379845). Immunohistochemistry and Digital Pathology for immune biomarkers and for Immunoscore (CD3/CD8) were analyzed. Gene expression profiling and pre-optimized immune-gene signatures called Immunosign were also used. Results: A significant increase of T cells (CD3+, CD8+) and a marked increase of CD103+ immune cell infiltration post- vs pre-treatment were observed for NBTXR3 + RT ( P< 0.01), while no differences were seen for RT. Post-treatment, an increased Immunoscore (CD3 + CD8 cell densities) was observed for NBTXR3 + RT compared to RT (P < 0.07). Consistently, the up-regulation of pan immune genes expression and specifically expression of adaptive immunity genes between pre- and post-treatment, was pronounced for NBTXR3 + RT when compared to RT. Functional analysis of genes up-regulated in NBTXR3 + RT showed an enrichment of cytokine activity (IL7, IFNA, IL16, IL11, IFNG), adaptive immunity (RAG1, GZMA, TAP1, TAP2, TBX21, STAT4, IFNG, LCK, LTK, CD37, CD22) and T cell receptor signaling pathway (CD28, CTLA4, CD274, BTLA, TIGIT, CD40LG, CD5, CD3E, ZAP70). Conclusions: NBTXR3 + RT induces a specific adaptive immune pattern. As such, it may contribute to convert “cold” tumor into “hot” tumor and be effectively combined with immunotherapeutic agents across oncology. These data warrant more tissue samples evaluation to reinforce these findings.
5 x 5 Gy and consolidation chemotherapy vs long-course preoperative chemoradiation for locally advanced rectal cancer: An interim analysis of a randomized phase III study.
Authors: Jin Jing , Liu Shixin , Zhu Yuan , Wang Wenling , Wang Xin , Wang Jun , Li Gaofeng , Fan Lin , Zhang Kuan , Shi Mei , Tang Yuan , Zhang Haizeng , Chi Yihebali , Zhou Ai-Ping , Huang Jing , Zhang Hongmei , Jiang Liming , Jiang Jun , Zou Shuangmei , Li Ye-Xiong 
Published: September 2018

e15006 Background: To present an interim analysis of a phase III trial comparing short-course radiotherapy followed by chemotherapy with long-course chemoradiotherapy in locally advanced rectal cancer. Methods: Patients with distal or middle third, MRI diagnosed cT3-T4 or N+ rectal adenocarcinomas were randomized to either 5 x 5 Gy and 4 courses of CAPOX (experimental group) or 50 Gy delivered in 25 fractions given concurrently with capecitabine (control group). Total mesorectal excision (TME) in both groups was performed 6-8 weeks after neoadjuvant treatment. This is an interim analysis of acute toxicities for the first 127 patients who finished neoadjuvant therapy, as well as the pCR and surgical complications for the first 100 patients who received surgery. Results: From 08/30/2015 to 12/11/2016, 63 patients in experimental group and 64 in control group from 10 Chinese hospitals were analyzed. During preoperative treatment, any acute toxicities were 100% in both groups and grade III-IV 19.0% vs. 6.3% ( p= 0.03) in experimental group and control group, respectively. Full-dose completion rates of planned neoadjuvant treatment were 88.9% and 93.7% in each group ( p= 0.33), respectively. After median duration of 7 weeks and 9 weeks in experimental group and control group, TME was performed. Among the 100 patients who have finished surgery, 94.1% and 89.8% in experimental and control group had R0 resection ( p= 0.426), while 21.6% and 6.1% of them achieved pCR ( p= 0.026), respectively. There were 8 patients in experimental group diagnosed as clinical CR and refused to further radical surgery, while, none in control group ( p= 0.003). The incidences of surgical complications were similar between two groups (experimental 29.1% vs. control 26.5%; p= 0.748), with perineal healing delay as the main reason. Conclusions: The acute toxicity and surgical complication were acceptable and comparable in both groups, however, the people in experimental group showed a significantly clinical and pathological response. The short-course irradiation and consolidation chemotherapy maybe an alternative standard of care, though the final result is in prospect. Clinical trial information: NCT02533271.
Adoptive transfer of NK cells in combination with chemotherapy to improve outcomes of patients with locally advanced colon carcinoma.
Authors: Li Lingyu , Cui Jiuwei , Wang Chang , Wang Yizhuo , Niu Chao , Yao Cheng , Tian Huimin , Jin Haofan 
Published: September 2018

e15038 Background: The prognosis of advanced colon cancer (CC) patients remains disappointing, partly due to their greater proportion of CC-initiating cells (CICs), which is responsible for cancer drug-resistance and immune escape. Immunotherapies by harnessing the immune system to eliminate tumors have attracted broad attention. This study was to detect whether chemotherapy could enhance cytotoxicity of natural killer (NK) cells to CC cells (CCs), especially for CICs in vitro, and further evaluate the efficacy and safety of NK-cell therapy combined with chemotherapy in patients with local advanced CC. Methods: We observed that cytotoxicity of NK cells to CCs and CICs pretreated with 5-Fu or oxaliplatin. Then, an open-label pilot cohort study was conducted with local advanced CC patients who had received surgical excision. 60 patients elected to receive either NK-cell therapy combined with chemotherapy (NK-cell group, 27 patients) or pure chemotherapy (control group, 33 patients). Progression-free survival (PFS), overall survival (OS) and adverse effects were investigated. Results: Chemotherapy sensitized CCs and CICs to NK cell lysis through upregulation of their NK cell activating ligands and reducing inhibitory ligands. Poorly differentiated CCs were more susceptible to NK-cell than well-differentiated CCs, and CICs were more easily to be killed by NK cell than their differentiated CCs. In the cohort study, the 5-year PFS and OS rates in the NK-cell group were significantly higher than those in the control group (51.1% vs. 34.9%, p= 0.043; 73% vs. 51.3%, p= 0.038, respectively).Among patients with poorly differentiated carcinomas or low expression of HLA-1, median PFS in the NK-cell group vs. the control group was 23.5 vs. 11.5 months ( p= 0.047), and median OS was 30 vs. 15 months ( p= 0.043), respectively. No significant adverse reaction was found during NK-cell therapy. Conclusions: NK-cell therapy in combination with chemotherapy in locally advanced CC prevented recurrence and prolonged survival with acceptable adverse effects, especially for poorly differentiated carcinomas.
A phase II study of capecitabine, oxaliplatin and irinotecan (XELOXIRI) as salvage therapy in patients with refractory metastatic colorectal cancer.
Authors: Kwok Gin Wai , Leung Roland Ching-Yu , Chiu Joanne , Tang Vikki , Yau Thomas Cheung 
Published: September 2018

e15049 Background: Advanced colorectal cancer (CRC) refractory to oxaliplatin, irinotecan, and fluoropyrimidines is associated with poor prognosis. The triplet combination of 5-fluorouracil, oxaliplatin, and irinotecan has shown efficacy and tolerability in treatment-naive disease. We investigated the efficacy and tolerability of salvage capecitabine, oxaliplatin and irinotecan (Xeloxiri) in patients who progressed on standard chemotherapy. Methods: This prospective phase 2 study with a primary endpoint of overall response rate (ORR) recruited patients with advanced CRC that have progressed on standard chemotherapy containing fluoropyrimidines, oxaliplatin, and irinotecan either as monotherapy or doublets. Prior use of anti-VEGF, and anti-EGFR agents were allowed. Patients received capecitabine 1250mg/m2 twice daily on day 1-7, oxaliplatin 85mg/m2 and irinotecan 165mg/m2 on day 1 every 2 weeks until disease progression or intolerable toxicity. Secondary endpoints were progression free survival (PFS) and overall survival (OS). Results: Between July 2011 and May 2016, we recruited 32 patients. Median age was 57 and the median number of treatment cycles was 6. 16 patients (50%) were K-RAS wild-type (WT), of which 6 were also N-RAS WT. The ORR was 25% and the clinical benefit rate was 56%. 87.5% of patient received targeted therapy prior to study entry. 34% of patients had > 3 previous lines of therapy. Median PFS and OS were 5.0 months (95% CI 3.2 - 7.1) and 10.4 months (95% CI 7.2 - 11.4) respectively. K-RAS mutation status, number of lines of previous therapy, and site of primary tumour were not predictive of ORR, PFS or OS on univariate testing. Treatment-related adverse events (AEs) occurred in all patients, with the majority being hematological. Dose reductions occurred in 87.5% of patients. 59% required dose delays, and 56% received granulocyte-colony stimulating factor. Grade 3/4 AEs included neutropenia (34%), anemia (16%), thrombocytopenia (12.5%), febrile neutropenia (9%), diarrhea (6%), and anorexia (3%). Conclusions: Xeloxiri is efficacious and safe in patients with chemo-refractory CRC and is a promising treatment strategy as salvage. Clinical trial information: in progress.
Association of microsatellite instability with distinct clinical and molecular characteristics in resected colon cancer: Analysis of a platform trial of the AIO colorectal study group—Colopredict Plus.
Authors: Reinacher-Schick Anke C. , Juette Hendrik , Noepel-Duennebacke Stefanie , Arnold Dirk , Basara Nadezda , Boehner Hinrich , Dahm Thorsten , Feder Inke Sabine , Hansen Olaf , Hiller Wolfgang , Leins Alexander , Müller Lothar , Ueberrueck Torsten , Teschendorf Christian , Trenn Guido , Verdoodt Berlinda , Zwingmann Nadine , Uhl Waldemar , Tannapfel Andrea 
Published: September 2018

e15086 Background: High microsatellite instability (MSI-H) is a prognostic marker in resected colon cancer (CC) identified in post-hoc analysis of multiple trials. However, validation in real-life cohorts and its association with clinical and molecular markers is lacking. Methods: In Sep 2013 we started a platform trial in 49 German cancer centers recruiting patients with UICC stage II and III CC diagnosed between 2008 to 2016. MSI was tested by immunohistochemistry (IHC) of mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. In case of any loss of protein expression (IHC neg), fragment length analysis (FLA) was performed, defining MSI high tumors (MSI-H) and MS stable tumors (MSS). Besides, mutations in known prognostic factors for CC such as RAS, BRAF, PI3K and others were determined by next generation sequencing (NGS). Results: By end of 2016, 1249 patients have been recruited into the trial: median age 73yrs., stage II/III: 686/563 pts. So far, tissue was analysed in 512 pts. Of these, 182 pts. were IHC neg with 116 pts. tested MSI-H upon FLA (22.7%). Median age was 73yrs., female/male: 260/252 pts., stageII/III: 292/220 pts. Association of MS status with clinical factors is shown in Table 1. Upon NGS analysis we found 16.3% BRAF mutations, 39% KRAS mutations, 2.8% NRAS mutations and 22.6% PI3K mutations. MSI-H status was significantly associated with BRAF mutation and wildtype status of RAS. Conclusions: We found a higher percentage of MSI-H cancers in our registry compared to reported data from randomised trials, possibly related to a higher median age in this real-life cohort. MSI-H was associated with female sex, primary tumor site, and distinct molecular markers and should therefore be considered a heterogeneous subgroup of CC. Updated analysis including NGS data and survival will be presented at the meeting. Clinical trial information: AIO- KRK-0413, DKRS:00004305. [Table: see text]
Genomic overview of right-sided and left-sided colorectal cancer using comprehensive genomic sequencing.
Authors: Shimada Yoshifumi , Kameyama Hitoshi , Nagahashi Masayuki , Ichikawa Hiroshi , Yagi Ryoma , Tajima Yosuke , Yuza Kizuki , Nakano Masato , Nakajima Masato , Ishikawa Takashi , Sakata Jun , Kobayashi Takashi , Nogami Hitoshi , Maruyama Satoshi , Takii Yasumasa , Ring Jennifer E. , Lyle Stephen , Okuda Shujiro , Takabe Kazuaki , Wakai Toshifumi 
Published: September 2018

e15101 Background: Although the difference in right vs. left sidedness of colorectal cancer (CRC) in response to targeted therapy has been reported, we hypothesized that right-sided colorectal cancer (RCC) is more likely to have genetic alterations associated with resistance of anti-EGFR therapy. We tested this hypothesis using comprehensive genomic sequencing (CGS) on a set of samples from well-characterized CRC patients. Methods: Two-hundred-one primary colon cancer patients with either RCC or left-sided colorectal cancer (LCC) were analyzed. We investigated gene alterations using 415 gene panel, which includes the gene alterations associated with resistance of anti-EGFR therapy: TK receptors ( ERBB2, MET, EGFR, FGFR1, and PDGFRA), RAS pathway ( KRAS, NRAS, HRAS, BRAF, and MAPK2K1), and PI3K pathway ( PTEN and PIK3CA). We defined the patients who had no alterations in any of the genes as “all wild-type”, who are theoretically considered as responders of anti-EGFR therapy. Other patients with genetic alterations in resistance pathways were defined as “mutant-type”. Results: Fifty-six patients (28%) and 145 patients (72%) had RCC and LCC, respectively. Mutation of PIK3CA, BRAF, ACVR2A, MSH6, and CTNNB1 were significantly associated with RCC. Conversely, mutation of APC and TP53 were significantly associated with LCC. Regarding the gene alterations associated with anti-EGFR therapy, only 6 of 56 patients (11%) of RCC were “all wild-type”; in contrast to 41 of 145 patients (28%) of LCC that were “all wild-type” ( P = 0.009). In 45 Stage IV patients treated with anti-EGFR therapy, RCC showed significantly worse progression-free survival (PFS) than LCC ( P = 0.019), and “mutant-type” RCC showed worse PFS compared to the others ( P = 0.018). Conclusions: RCC is more likely to have the genetic alterations associated with resistance of anti-EGFR therapy compared to LCC. Primary tumor sidedness is a surrogate for the non-random distribution of molecular subtypes in CRC.
The relationship between Pim-3 expression and chemoradiotherapy resistance in locally advanced rectal cancer patients.
Authors: Zhang Rong-xin , Zhou Zhongguo , Lu Shi-xun , LU Zhen-hai , Wan Desen , Pan Zhi-zhong , Wu Xiao Jun , Chen Gong 
Published: September 2018

e15112 Background: It is difficult for clinical oncologists to predict which types of rectal cancer patient would respond to neoadjuvant chemoradiotherapy. About 30% of rectal cancer patients who could not benefit from chemoradiotherapy, and about 10% of patients even suffered from disease progression. It is of considerable importance to identify a bio-marker to identify patients who would benefit from neoadjuvant treatment. Methods: This study enrolled 175 rectal cancer patients who underwent neoadjuvant treatment. Tissue samples from all the patients were deposited in the tissue bank of Sun Yat-sen University Cancer Center prior to neoadjuvant treatment. We compared the expression of Pim-3 in rectal tumors and investigated correlations with the response to chemoradiotherapy and with survival. Results: The Pim-3-negative patients were more likely to achieve a pathological complete response to chemoradiotherapy (P = 0.001, RR = 5.132, 95% CI: 2.442–10.787). Cox multivariate analysis in 137 patients with at least 24 months follow-up showed that the expression of Pim-3 (P = 0.041, RR = 1.209, 95% CI = 1.007–1.452) and cycles of neoadjuvant chemotherapy cycles (P = 0.006, RR = 0.557, 95% CI = 0.367–0.845) were significant factors affecting the survival status of patients. Cox multivariate analysis of disease-free survival showed that Pim-3 expression (P = 0.012, RR = 1.180, 95% CI: 1.037–1.344) and adjuvant chemotherapy cycles (P = 0.003, RR = 0.745, 95% CI: 0.615–0.902) were statistically significant factors. Conclusions: Pim-3 could be a potential predictive bio-marker of the response to chemoradiotherapy.
Mucinous colorectal carcinoma: A single center experience.
Authors: Oksuzoglu Berna , Zengin Guliz , Turker Ibrahim , Demirci Umut 
Published: September 2018

e15116 Background: The aim of this study was to evaluate the clinical features and treatment outcomes of mucinous colorectal adenocarcinoma (MCA) followed in a single institution. Methods: Seventy-nine patients diagnosed with MCA admitted to our center between January 2003 and August 2016 included in this study. Demographic and clinico-pathologic characterictics of patients were analysed using patient medical records retrospectively. Results: Median age of the patients was 57 (24-83) with a male to female ratio of 1/3. Common symptoms were abdominal pain, rectal bleeding, abdominal distention, tenesmus and constipation in 44 (55.7%), 17 (21.5%), 7 (8.9%), 6 (7.6%), 5 (6.3%) of patients respectively. At the time of the diagnosis ECOG performance score was 0 or 1 in 74 (93.7%) of the patients. One (1.3%), 26 (32.9%), 37 (46.8%) and 15 (19%) of the patients had stage 1,2,3 and 4 disease respectively. Neoadjuvant chemo-radiotherapy with 5 FU and leucovorin (FUFA) was the treatment of choice in 11 (13.9%) of rectal MUC patients. The type of surgery was curative, palliative and emergent in 60 (76%), 9 (12.4%) and 9 (12.4%) respectively. Localisation of the primary tumor was right colon, left colon and rectum in 31 (39.2%), 30 (38%) and 18 (24.8) patients respectively. In the adjuvant setting, 59 (74.7%) of patients were received adjuvant chemotherapy. Only 6 patients had MSI, 26 patients had k-RAS, n-RAS and b-RAF mutation results. Metastatic sites were mostly visceral organ, intra-abdominal and local recurrence in 13 (16.5%), 12 (15.2%) and 6 (7.6%) of patients respectively. The median disease free survival, progression free survival and overall survival (OS), were 15.5 months, 17.5 months and 44.1 months, respectively. Conclusions: Survival rates were higher than literature in this study. This may be partly explained by better ECOG performance score of our patient group. We also found that better ECOG score, left sided tumor, younger age, were associated with better OS.