bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gefitinb along with methotrexate as palliative therapy in PS 3 and above in metastatic esophagus squamous cell carcinoma with focus on Q-TWIST.
Authors: DUSI VIDYA SAGAR , C Obul Reddy , Attili Suresh VS , Palanki Satya Dattatreya 
Published: February 2020

355 Background: Metronomic therapy is proven method for treatment of terminally ill patients with malignancy, who are not fit for chemotherapy. The median PFS was significantly superior in responders in previous Indian experiences. However most of them were done in head and neck cancers.The prognosis of patients with metastatic esophageal cancer remains poor with only option being symptomatic care. As the previous experiences show metronomic therapy is safe among various options and there is no study focusing on Quality-Adjusted Time Without Symptoms or Toxicity (Q-TWiST) in southern Indian population,we thought of evaluating the same. Methods: Details of 42 subjects with refractory or progressive metastatic squamous cell carcinoma esophagus having PS > 2 were evaluated. Case records between 2017 September and 2018 September were analyzed for TWIST and QOL. Patients received Gefitinib (250 mg/day), Methotrexate 15 mg IM weekly or in combination. Patients were stratified into those with improved PS and those without. The subjects without PS improvement were continued on the single agent and those with improvement were offered additional chemotherapy based on physician/ patient preference. Metronomic therapy could be continued beyond disease progression- if there is TWIST/QOL improvement. Results: Out of 42 subjects, 29 had improvement in the PS and were continued later. 9 had stable PS and disease. 4 had worsening of PS. 34 subjects have clinically meaningful response (stable disease + complete + partial responses) and had symptomatic improvement. The median number of cycles was 6 (4–11). The median PFS was 198 days (95% CI, 174 to 214), and the median improvement in QOL was 6 points on a scale of 25. Grade II/IV toxicities were observed in 21 (50%) cases predominantly skin rash, stomatitis and diarrhea. Conclusions: Metronomic therapy is well tolerated and may have a role in the treatment of advanced cancers with poor performance status. 67% of the patients who are otherwise not eligible for any active therapy became eligible and had better QOL and longer PFS, which re-emphasizes role of metronomic therapy in advanced squamous cell carcinoma of esophagus.
Hyperprogressive disease during nivolumab chemotherapy in metastatic gastric cancer: Multicenter retrospective study in Japan.
Authors: Suzuki Takeshi , Aoki Masahiko , Shirasu Hiromichi , Takahashi Naoki , Nakatsuka Rie , Ando Takayuki , Kito Yosuke , Yamamoto Yoshiyuki , Kawakami Kentaro , Matsumoto Toshihiko , Shimozaki Keitaro , Nagase Michitaka , Yamaguchi Toshifumi , Negoro Yuji , Tamura Takao , Amanuma Yusuke , Esaki Taito , Miura Yuji , Nagashima Kengo , Boku Narikazu 
Published: February 2020

377 Background: Nivolumab has demonstrated a survival benefit for advanced gastric cancer (AGC). However, hyperprogressive disease (HPD) has been reported in various cancers. Methods: The subjects of this retrospective study were AGC patients with measurable disease who received nivolumab, and their tumors were assessed at least 3 times (during prior therapy, before and after nivolumab) in 24 institutions. Tumor growth rates (TGR) during nivolumab were compared to those during prior therapy as reported (Champiat S, 2017). HPD was defined as an increase in TGR > 2-fold. Results: 218 patients were identified as the subjects. While 33 (15.1%) partial response (PR) were achieved, 130 patients (59.6%) showed progression disease (PD), 38 of whom were classified as HPD (17.4%) and 2 patients showed pseudo progression (1.0%). The median progression-free survival (PFS) was 1.9 months (95% CI: 1.9–2.4) and the median overall survival (OS) was 8.5 months (95% CI: 7.1–9.6) in all patients. While patients with PD showed shorter prognosis compared with non-PD patients (median PFS: 1.5 months vs 6.4 months, hazard ratio; 6.0 [95% CI: 4.3–8.4]; p < 0.0001; median OS: 4.7 months vs not reached, hazard ratio; 4.1 [95% CI: 2.8–6.3]; p < 0.0001), there were no differences either in PFS or OS between patients with HPD and those with PD other than HPD (median PFS: 1.5 months vs 1.6 months, hazard ratio; 1.3 [95% CI: 0.9–2.0]; p = 0.1194; median OS: 5.0 months vs 4.6 months, hazard ratio; 1.0 [95% CI: 0.6–1.5]; p = 0.8695). Histological type, liver metastases, carbohydrate antigen 19-9 (CA19-9) level were associated with HPD. Conclusions: HPD was observed 17.4% in AGC patients treated with nivolumab. There were no differences either in PFS or OS between patients with HPD and those with PD other than HPD. Clinicopathological characteristics might be a predict factor for HPD.
Palliative systemic chemotherapy with or without pressurized intraperitoneal aerosol chemotherapy with cisplatin and doxorubicin (PIPAC C/D) for gastric cancer with peritoneal metastasis: A propensity score analysis.
Authors: Khomiakov Vladimir , Meisner Christoph , Ryabov Andrey , Bolotina Larisa , Utkina Anna , Kolobaev Ilia , Sobolev Dmitry , Chayka Anna 
Published: February 2020

380 Background: Gastric cancer (GC) with peritoneal metastasis (PM) has a dismal prognosis. Palliative systemic chemotherapy (SC), usually doublet combinations of platinum and fluoropyrimidines, is the standard of care. Pressurized IntraPeritoneal Aerosol Chemotherapy with Cisplatin and Doxorubicin (PIPAC C/D) yields promising results. Here we aimed to compare overall survival (OS) between SC + PIPAC C/D vs. SC alone in patients with PM from GC. Methods: Prospective cohort of 95 consecutive patients with PM from GC treated in palliative intent at our institution from 2010 to 2018. Of these patients, 69 received SC + PIPAC C/D („PIPAC“), 26 SC alone („control“). Choice of treatment was not dictated by medical criteria, but by (non-) availability of the single-use medical devices needed for PIPAC in Russia. All patients received doublet or triplet chemotherapy with platinum together with fluoropyrimidines or capecitabin. A Cox proportional hazard model based on propensity score (PS) was used to assess the effect of PIPAC on OS and account for confounding factors. Results: The HR adjusted for PS for PIPAC vs. control was 0.396 (CI 5- 95% = 0.224-0.700, p-value 0.001). In the simple (unadjusted) Kaplan-Meier, median survival in the control group was 7.0 months (CI: 4.51 - 9.49) and in the PIPAC group 14.0 months (CI: 11.46-16.54). In the control group, all 26 patients died after 1-25 months. In the PIPAC group, 36 of 69 patients died after 4 to 20 months. The longest observed survival time in the PIPAC group was 27 months. Significance for the log-rank test after Mantel-Cox (not adjusted) was p < 0.0001. Conclusions: Compared with SC alone, intensified chemotherapy combining PIPAC C/D and SC doubled OS. These promising results need to be confirmed in a randomized trial.
Magnetic marking clip for easier laparoscopic localization of small gastrointestinal tumors.
Authors: Kim Sang Hoon , Keum Bora , Jeon Han Jo , Jang Se Hyun , Lee Kang Won , Kim Sanghyun , Choi Seong ji , Lee Jae Min , Choi Hyuk Soon , Kim Eun Sun , Jeen Yoon Tae , Lee Hong Sik , Chun Hoon Jai , Kim Chang Duck 
Published: February 2020

386 Background: Laparoscopic surgery for gastrointestinal tumors requires fast and precise tumor localization. As tumor palpation is not possible during laparoscopic surgery, tumor identification is often difficult for some cases. Despite various methods, such as tattooing or endo-clipping, have been introduced for the localization of tumors, these methods own clear limitations. To overcome the drawbacks of these conventional marking methods, we designed a magnetic marking device linked to an endo-clip(MMC, Magnetic Marking Clip) for endoscopy. We performed preoperative endoscopic clipping with MMC and analyzed the intraoperative localization efficacy and safety during laparoscopic surgery. Methods: Study enrolled 30 patients with gastric and colorectal neoplasms scheduled to undergo endoscopic clipping before laparoscopic surgery at the Korea University Medical Center, Korea, between August 2017 and June 2019. A silicone-coated high-power neodymium marking device (ring or rod type) was fixed together with an endo-clip and applied on the center of the lesion during preoperative endoscopy. During laparoscopic surgery, a detecting magnetic body was inserted through a laparoscopic trocar and was used to localize the tumor that is marked with MMC. The time needed for endoscopists to place MMC at the lesion, laparoscopic clip detection time and success rate were studied. Results: Endoscopists placed MMC within 30 seconds. It was possible to find MMC in all cases of laparoscopic surgery. Time needed to find the MMC laparoscopically was relatively shorter than the time conventionally taken just with an endo-clip itself. There was no reported dislodgement of the clip before the surgery or any other adverse events associated with the MMC procedure. Conclusions: The MMC method enabled simple and fast tumor localization and showed excellent outcomes in efficacy of tumor localization. The MMC method may help surgeons localize GI tumor lesions easily and safely during laparoscopic surgery.
Real-world efficacy and biomarker of nivolumab for advanced gastric cancer.
Authors: Kawabata Ryohei , Kurokawa Yukinori , Hagi Takaomi , Omori Takeshi , Matsuyama Jin , Fujitani Kazumasa , Hirao Motohiro , Akamaru Yusuke , Takahashi Tsuyoshi , Yamasaki Makoto , Satoh Taroh , Doki Yuichiro 
Published: February 2020

388 Background: Although nivolumab demonstrated survival benefit and a manageable safety profile in previously-treated advanced gastric cancer in a phase III trial (ATTRACTION-2), the efficacy of nivolumab in real-world and predictive factors of responses to nivolumab for advanced gastric cancer remain unclear. We evaluated the efficacy of nivolumab and compared clinicopathological characteristics with responses to nivolumab and long-term survivals in patients with gastric cancer. Methods: 205 patients with unresectable or recurrent gastric cancer who were treated with nivolumab as 3rd or more line treatment were enrolled from 23 institutions. Tissue specimens were collected in 199 patients. PD-L1 expression of tumor specimens defined as tumor positive score (TPS) and combined positive score (CPS) and mismatch repair (MMR) were analyzed by immunohistochemistry. Tumor responses were assessed according to RECIST version 1.1. Hyper progressive disease (HPD) was defined as ≥two folds increase in tumor growth rate. Results: 138 out of 205 enrolled patients had measurable lesions. Response rate and HPD rate were 16.7% (23/138) and 22.0% (29/132), respectively. Response rate was significantly higher in patients with performance status (PS) 0-1, non-peritoneal diseases, CPS ≥10, and MMR deficient patients. On the other hand, PS 2-3 and liver metastases were predictive factors of HPD. Patients with CPS≥10 and MMR deficiency showed significantly better progression-free (P = 0.005, P = 0.001) and overall survivals (P = 0.005, P = 0.002). TPS showed no significant association with any outcomes. Conclusions: Real-world efficacy of nivolumab was shown in previously-treated advanced gastric cancer. CPS and MMR could be the useful biomarkers for the efficacy of nivolumab treatment as well as PS and metastasis site. Clinical trial information: UMIN000032164.
Retrospective analysis for efficacy and safety of nivolumab in advanced gastric cancer patients (pts) with malignant ascites.
Authors: Sugaya Akinori , Ueyama Shunsuke , Suzuki Hirosumi , Yamada Takeshi , Yamamoto Yoshiyuki , Moriwaki Toshikazu , Hyodo Ichinosuke 
Published: February 2020

392 Background: Nivolumab is a standard of care as the later-line therapy for advanced gastric cancer. However, there are few data about efficacy and safety of nivolumab for pts with malignant ascites. Methods: We conducted a multicenter retrospective study for pts with advanced gastric cancer who received nivolumab alone from Oct. 2017 to Feb. 2019. Pts were divided into two groups; high ascites burden (HAB) with moderate or massive ascites and non-HAB with none or a small amount of localized ascites at pelvis and/or liver surface. Results: A total of 72 pts (23 pts with HAB and 49 pts with non-HAB) were evaluable. The HAB group had more pts with young (median 62 vs 70 years), female (35 vs 14 %), no prior gastrectomy (63 vs 35 %) and poor performance status (PS > 1; 26 vs 10 %), compared to the non-HAB group. Disease control rate was 44% (95% CI 23-64%) in the HAB group and 57% (95% CI 43-71%) in the non-HAB group. Ascites decreased in 4 pts (17%) and completely disappeared in 2 pts (8.7%) in the HAB group. These 6 pts were all male and had prior ramucirumab treatment with a mean neutrophil-lymphocyte ratio 2.1 (from 0.85 to 3.7) at the initiation of nivolumab. After 5 months of follow up period, disease progression or death events for progression-free survival (PFS) occurred in 74% of the HAB group and 53% of the non-HAB group. Median PFS was 1.0 (95%CI 0.5-1.5) and 2.6 (95%CI 0.9-7.4) months in pts with HAB and non-HAB, respectively. PFS rates at 6 months were 31% in the HAB group and 33% in the non-HAB group. Immune-related adverse events occurred in 26% of the HAB group and 16% of the non-HAB group including one and two pts with grade 3 or 4 events, respectively. There was no treatment-related death in both groups. Conclusions: Although pts with HAB showed trends of worse outcomes compared with those with non-HAB, nivolumab was suggested to provide a survival benefit to some pts with HAB, and was tolerable in the HAB group.
Propensity score regression analysis of esophageal cancer treatment with surgery alone or neoadjuvant chemotherapy.
Authors: Lewis Wyn Griffith , Powell Arfon GMT , Christian Adam 
Published: February 2020

405 Background: The aim of this study was to examine the outcomes of oesophageal adenocarcinoma (OC) treatment with either surgery alone (S), or with neoadjuvant chemotherapy (NAC) followed by surgery (NACS), by means of propensity score (PS) regression analysis, in order to examine whether the benefits reported in the MRC OE02 trial were reproducible in UK cancer network clinical practice. Methods: Consecutive patients undergoing potentially curative treatment for OC in a regional cancer network were studied. Multiple regression models, including PS were developed to account for confounding factors and the primary outcome measure was disease-free (DFS) and overall survival (OS). Results: A cohort of 440 patients was included in a regression analysis controlling for confounders (176 S, 264 NACS). NACS was associated with positive margin status (NACS vs. S, 42.4% vs. 26.7%, p<0.05), poor 5-year DFS (32.1% vs. 56.9, p<0.001), and poor 5-year OS (27.5% vs. 47.3%, p<0.001). On regression adjustment based on propensity scores, NACS was not associated with DFS (p=0.220) or OS (p=0.431). Mandard tumour regression grade (TRG) was significantly associated with DFS (hazard ratio (HR) 0.21,95% CI 0.07-0.70) and OS (HR 0.27 (95% CI 0.13-0.59). Five-year DFS and OS related to TRG was 63.6 and 61.5% vs. 8.0 and 8.6% (p<0.001) for good and poor responders respectively. Conclusions: Prescribing NAC to all OC patients risks delay in effective treatment of patients who are relatively chemo-resistant, given the variabilityin pathological response. Identifying OC patients who derive the most NAC benefit should be the focus.
Neoadjuvant chemotherapy (TPF regimen) followed with robotic surgery and its impact on outcome in management of esophageal cancers: Indian experience.
Authors: Somashekhar S.P. , C. Rohit Kumar , Rajgopal Ashwin K. , Rauthan Amit , Patil Poonam 
Published: February 2020

407 Background: Neo-adjuvant chemotherapy coupled with robotic three stage esophagectomy have shown promising results in esophageal cancer. Methods: 136 patients diagnosed with squamous cell cancer esophagus were included to analyze the benefit of NACT with DCF (docetaxel 75mg/m2 day 1, cisplatin 75mg/m2 day 1, 5-FU 750mg/m2 per day 1-4) regimen 3 cycles followed by three stage robotic esophagectomy. Esophagus, assessed by EUS and PET-CT scan, pre-chemo and post-chemo, in biopsy proven Squamous cell Carcinoma Oesophagus. All the data pertaining to chemotherapy and surgery were prospectively maintained in a data base. Results: Median age 62.7 years, male to female 5.9:4.1. T2 4%, T3 90% & T4 6%. N0 10% & N+90%. Post NACT, Partial response of 50.8%, and a complete pathological response of 27.6% was observed with response rate of 66.3%. 20 pts. had mucositis, but none had grade 3 toxicity, neutropenia in 24 pts. and febrile neutropenia in 7 pt., vomiting and fatigue in 35 pts. Mean blood loss 256.5±85.8ml, duration of surgery 322.4±28.4min, ICU stay 1.5±0.8-day, hospital stay 10.5±2.1 day. Proximal and distal margin was negative for all whereas only 2 patients had a positive CRM. Mean Lymph node yield was 22.4±3.5 nodes. All patients had complete robotic surgery with no conversions and major intraoperative complication. Post-operatively Minor complication was noted in 5 patients temporary vocal cord palsy, 10 delayed gastric emptying, wound infection in 3 and minor lung infection 9. Major complication in form of leak (3), stenosis (5), chylous leak (4) was noted. 30-day mortality 4.5%. With the longest follow up of 50 months, 3 year DFS and OS was 75.4% & 68% respectively. Conclusions: Neoadjuvant chemotheraphy with TPF regimen showed excellent response rates with minimal G3 toxicity and is well tolerated in Indian patients. Combination of NACT with robotic esophagectomy has excellent outcome with low morbidity & mortality.
Gene mutations distinguishing gastric from colorectal and esophageal adenocarcinomas.
Authors: Hoang Tuyen , Hiyama Darryl , Dayyani Farshid 
Published: February 2020

424 Background: Genetic analysis of gastrointestinal malignancies shows a great number of mutations. Most mutations found in gastric tumors are found in colorectal and esophageal tumors, and vice versa. The challenge remains to identify mutations that distinguish gastric from colorectal and esophageal cancers. Using open-access cancer genomics data, we sought to identify mutations that accounted for the unique phenotypic features of gastric tumors. Methods: Thirteen cancer genomics datasets with demographic, clinical, and genetic variables were analyzed. Each subject was flagged with or without a mutated gene. For each anatomical location, pathologic stage and histology were compared between subjects with and without a specific mutated gene, using two-sample t tests, adjusted for multiple gene testing. Results: Analysis included 1,915 subjects with valid pathologic stage and histology. Mean age was 68 years (SD=10). About 54% were female. The most common race was Caucasian (37%) while minorities were rare with high rate of missing data (44%). Pathologic stage: 20% stage I, 35% stage II, 31% stage III, and 14% stage IV. Anatomical location: 29.5% gastric, 59.5% colorectal, and 11.0% esophageal. Histology of gastric cancer: 61.4% intestinal, 23.2% diffuse, 14.9% others, and 0.5% missing. One gene–HEATR7B2–though rarely mutated, occurred only in stage IV of gastric tumors. Two mutated genes–CDH1, RHOA–distinguished diffuse from intestinal gastric histology. One mutated gene–CDH1–distinguished gastric from colorectal and esophageal tumors. Conclusions: This study confirmed the genes involved in the pathogenesis of gastric malignancies (CDH1, RHOA) and linked one novel gene to stage IV of gastric tumors (HEATR7B2). Future animal and human epidemiologic studies are needed to elucidate how this novel gene contributes to gastric malignancies.
Slug overexpression and association with clinicopathological features in gastric cancer.
Authors: Kim Joori , Kim In-Ho , Lee Han Hee , Lee Sung Hak , PARK Jae Myung 
Published: February 2020

426 Background: Slug is a suppressive transcriptional factor of E-cadherin, acting as an activator of epithelial-mesenchymal transition(EMT). Its clinical relevance in gastric cancer(GC) is not fully known. Methods: Our study evaluated the expression patterns of EMT and cancer stem cell markers in GC patients who had clinical stage 2-3, underwent gastrectomy, D2 lymph node dissection (LND), adjuvant chemotherapy. Immunohistochemistry of E-cadherin, vimentin, CD133, ABCG2, NEDD9, SMAD4, XB130, Slug, Snail were investigated from 210 gastric cancer samples using tissue microarrays. The correlation between each markers expressed and the association with clinicopathological factors were analyzed. Results: Slug expression was more frequent in stage 3 than stage 2 (p=0.000), advanced T (p=0.007) and N stage (p=0.001), while histologic type did not make difference. Slug expression correlated with the expression of cancer stem cell marker CD133 (r=0.180, p=0.015) and CD133 expression was also related with ABCG2 (r=0.412, p=0.000). High Slug group showed shorter overall survival, compared to low Slug group (median OS 134 vs 124 months, p=0.044). The 2-year and 5-year disease-free (DF) rate for patients with high Slug and low Slug was 87.1% and 79.8%, 68.1% and 79.8%, respectively(p=0.038). The DFS curve reached an earlier plateau at 11-month in low Slug group, while in high Slug group took as long as 99 months. A multivariate analysis using the Cox proportional hazards regression model demonstrated Slug to be an independent prognostic factor for overall survival; hazard ratio 0.504 [95% CI 0.278-0.916] (p=0.025). Conclusions: In stage 2-3 GC patients who underwent gastrectomy with D2 LND and adjuvant chemotherapy, high Slug expression is associated with better disease-free and overall survival. Patients may benefit by testing Slug immunohistochemistry to predict prognosis after gastrectomy.