bluuebunny/crossref_metadata_2025_split huggingface dataset:
Conversion gastrectomy for stage IV unresectable gastric cancer: A retrospective cohort study.
Authors: Sagawa Tamotsu , Sato Yasushi , Hamaguchi Kyoko , Hirakawa Masahiro , Nagashima Hiroyuki , Waga Eriko , Fujikawa Koshi , Takahashi Yasuo 
Published: February 2020

298 Background: Stage IV Gastric cancer (GC) is a heterogeneous biological condition with a mixture of distant metastases, including hematologic, lymph nodal and/or peritoneal. In the recent classification introduced by Yoshida et al with the proposal to identify objective principles for conversion surgery, stage IV GC patients were subdivided into 4 new categories. In this study, we retrospectively investigated the efficacy of conversion gastrectomy for stage IV GC patients, with particular focus on the Yoshida’s classification. Methods: A retrospective, single center cohort study was performed in patients who had undergone conversion gastrectomy between 2005 and 2018. Data were extracted from Hokkaido Cancer Center database including all metastatic gastric cancer patients submitted to surgery. Only stage IV unresectable tumors/metastases which became resectable after chemotherapy were included in this analysis. Results: Forty-two resected stage IV GC patients were included in this analysis. Median overall survival (OS) was 40.0 months and 1-, 3- and 5-year survivals were 92.9, 70.7 and 57.7%, respectively. Univariate analysis among the patients with conversion gastrectomy identified macroscopic type, clinical response to 1st line therapy, pathological tumor depth, pathological nodal stage, R0 resection as significant prognostic factors. The MSTs of the patients with conversion gastrectomy for each category were 50.1 months for category 1, 46.6 months for category 2, 22.7 months for category 3 and 17.2 months for category 4. Conclusions: Unresectable stage IV GC patients could benefit from radical surgery after chemotherapy and achieve long survivals. Adequate selection of stage IV GC patients for conversion therapy may be an important role.
Perioperative FLOT in resectable gastric cancer: Italian real-world data from the RealFLOT study.
Authors: Giommoni Elisa , De Vita Ferdinando , Pecora Irene , Iachetta Francesco , Strippoli Antonia , Satolli Maria Antonietta , Spallanzani Andrea , Puzzoni Marco , Stragliotto Silvia , Sisani Michele , Formica Vincenzo , Giovanardi Filippo , Pozzo Carmelo , Prisciandaro Michele , Di Donato Samantha , Petrillo Angelica , Catanese Silvia , Tirino Giuseppe , Lavacchi Daniele , Antonuzzo Lorenzo ,   On behalf of GOIRC (Gruppo Oncologico Italiano di Ricerca Clinica)
Published: February 2020

300 Background: Perioperative treatments have significantly improved survival in patients with resectable gastric cancer, increasing 5-year overall survival from 23% with surgery alone to 45% with FLOT (fluorouracil, oxaliplatin, docetaxel). Pathological regression is a prognostic marker of better survival. Methods: In this observational, retro- and prospective study we collected data from patients with resectable gastric or gastro-oesophageal junction (GEJ) adenocarcinoma treated, as clinical practice, with perioperative FLOT. All patients had clinical T2 or higher and/or nodal involvement, according to FLOT4-AIO trial. Results: A total of 206 patients received perioperative chemotherapy with FLOT at 15 Italian centres, between September 2016 and September 2019. Overall, 186 (90.3%) patients completed the preoperative phase, 190 (92%) underwent surgery, and 142 (68.9%) started the postoperative phase. Among patients who started the postoperative phase, 105 (51.0%) received FLOT, while 37 (18%) received less intensive regimens (e.g. FOLFOX or De Gramont), depending on performance status after surgery or toxicity in the preoperative phase. Pathological complete response (pCR) was obtained in 7.3% of cases. In the preoperative phase, grade (G) 3-4 hematological and gastrointestinal adverse events (AEs) were reported in 42 (20.4%) and 13 (6.3%) patients, respectively. Conclusions: These real data confirmed the feasibility of perioperative FLOT in a less-selected population, representative of the clinical practice. The pCR rate was lower than in the FLOT4-AIO trial. The survival outcomes, potential predictive or prognostic factors and comprehensive safety data will be included in the final analysis. [Table: see text]
Baseline features predicting receipt of chemotherapy in metastatic esophageal cancer: A National Cancer Database analysis of 12,370 patients.
Authors: Manguso Nicholas , Kim Sungjin , Hendifar Andrew Eugene , Klempner Samuel J. , Chao Joseph , Guan Michelle , Placencio-Hickok Veronica , Kim Haesoo , Liu Jar-Yee , Burch Miguel , Gangi Alexandra , Atkins Katelyn Mae , Kamrava Mitchell , Gong Jun 
Published: February 2020

316 Background: We investigated predictors for chemotherapy (CTX) and prognostic variables in a large metastatic esophageal cancer (mEC) patient data set. Methods: We interrogated the National Cancer Database between 2004-2015 and included patients (pts) with M1 disease who had known CTX status (received or did not receive CTX). Univariable and multivariable analyses were performed, and a logistic regression model was used to estimate the effect of CTX with adjustment for potential confounders. Results: We included 12,370 mEC patients with available CTX status for multivariable analyses. Predictors for CTX treatment included year of diagnosis 2010-2014 (odds ratio (OR) 1.29, 95% confidence interval (CI) 1.17-1.43), median income > $46,000 (OR 1.49, 1.27-1.75), and node-positivity (OR 1.35, 1.20-1.52; all p < 0.05), while female gender (OR 0.86, 0.76-0.98), black race (OR 0.76, 0.67-0.93), uninsured (OR 0.41, 0.33-0.52), and Charlson Comorbidity Index (CCI) ≥2 (OR 0.61, 0.50-0.74) predicted for lower odds of receiving CTX (all p < 0.05). Median OS for pts receiving CTX was 9.53 mos (9.33-9.72) vs. 2.43 mos (2.27-2.60) with no CTX (p < 0.001). Modeling the effect of CTX to OS using a time-dependent coefficient showed that CTX was associated with improved OS up to 10 months, after which there is no significant effect on OS. Independent predictors of OS included treatment at an academic center (hazard ratio (HR) 0.91, 0.87-0.94), CCI ≥2 (HR 1.16, 1.07-1.26), and uninsured status (HR 1.20, 1.09-1.31). Conclusions: We identified several predictors for receipt of CTX and OS in pts with mEC. The benefit of CTX on OS is time-dependent and favors early initiation. Focused outreach in lower income and underinsured patients is critical as receipt of CTX is associated with improved OS.
Morbidity associated to advanced gastric cancer and its impact on overall survival.
Authors: Meneses Medina Mónica Isabel , Valenzuela Ana Karen , Hernandez-Felix Jorge Humberto , Verduzco-Aguirre Haydee Cristina , Camargo Vanessa Rosas , Cortez Dominguez Edwin Ulises , Anaya Sánchez Luis Guillermo , Noguez-Ramos Alejandro , Huitzil Melendez Fidel David 
Published: February 2020

327 Background: Advanced gastric cancer (GC) is a disease with high morbidity and poor prognosis. We hypothesize that different sites of metastasis have different impact in terms of symptoms and complications. We sought to evaluate if site specific morbidity in our patients impacted treatment and survival. Methods: Medical records from patients with advanced GC treated from Jan 2005 to Dec 2015 were retrospectively reviewed. Morbidity was defined as having any symptom by metastases in a specific site. OS was estimated by Kaplan Meier method and compared by Log-rank test. P value < 0.05 was considered significant. Results: We included 180 consecutive patients, median age at diagnosis was 56 years (21-90), 55% were women. Most common sites of metastases were: peritoneum 76.1%, non-regional lymph nodes 38.9%, liver 22.8%, lung 26.7%, bone 9.4% and ovary 12.8%. Regarding morbidity, at diagnosis 68% of patients presented morbidity by the primary tumor: obstruction 56%, bleeding 27%, obstruction and bleeding 3%, other 14%. Disease by peritoneum caused morbidity in 30%, by lung in 8%, by ovarian in 4.4%, by lymph nodes in 3.3%, and by other sites in 5.6% of patients. OS in the global cohort was: 3.53 months (2.2 to 4.8), nevertheless by univariate analysis we found that OS was affected by morbidity at some sites as it is show in table. More patients with peritoneal morbidity could not receive treatment vs those without peritoneal morbidity (p = 0.042). Conclusions: We found that morbidity in peritoneum, lung and ovary adversely affected prognosis of patients with advanced GC. Moreover, peritoneal morbidity preclude patients from receiving oncological treatment. [Table: see text]
Patterns of gastric cancer metastasis within the United States.
Authors: Sirody Joseph , Kaji Amy H. , Hari Danielle M. , Chen Kathryn Tzung-Kai 
Published: February 2020

329 Background: There are few reports on the epidemiology of gastric cancer metastasis, although outcomes are known to be uniformly poor. Here we describe the patterns of gastric cancer metastasis and treatment in the United States (US). Methods: Patients with gastric adenocarcinoma histologies were identified in the National Cancer Database (NCDB) from 2004-2016. We describe univariate associations between different sites of metastasis and clinicopathologic characteristics and treatment modalities, using the chi-square and Kruskal-Wallis tests. Kaplan Meier curves were constructed for the estimation of overall survival (OS) by metastatic site. Results: Due to changes in the coding of metastatic disease, we were limited to the year 2016 for evaluation of patterns of disease. Twenty-six percent (n = 1228) of gastric cancer patients presented with liver metastases, 20% (n = 941) with distant nodes, 43% (n = 2028) with other distant site metastases (including peritoneum), and the rest to bone, brain or lung. On univariate analysis, when compared to liver metastases, other distant site metastases were significantly more likely to arise from an antral primary site (28% v. 16%); to be of Hispanic origin (16% v. 7%); female (42% v. 29%); associated with signet ring histology (34% v. 6%); lymphovascular invasion (LVI) (58% v. 27%); and tumor grade III/IV (85% vs. 60%) (p < 0.0001 for all). There were no significant differences in how patients with metastatic disease were treated in terms of systemic therapy. With regard to OS, due to how metastatic sites were coded prior to 2016, it was not possible to compare peritoneal metastases against other sites; however, patients with distant nodal disease had improved median overall survival compared to those with any other metastatic site (7.9 v. 5.2 months, p < 0.0001). Conclusions: The majority of US patients with metastatic gastric cancer present with presumed peritoneal disease. Predictive factors for peritoneal metastases vs. liver metastases included adverse prognostic features, including signet ring histology, higher tumor grades, and LVI. Although it was not possible to compare OS of peritoneal disease against other sites, continued follow up is needed, as this may impact future staging.
Safety, pharmacokinetics, and efficacy of RC48-ADC in a phase I study in patients with HER2-overexpression advanced solid cancer.
Authors: Gong Jifang , Fang Jianmin , Shen Lin 
Published: February 2020

334 Background: HER2 overexpression is common in many malignancies and contributes to tumor growth. Unlike the varied options of anti-HER2 target therapies for breast cancer, there is a huge unmet medical need for HER2 overexpressing non-breast solid tumor (NBST) such as gastric cancer and urothelial cancer. Therefore, we conducted the first study of RC48-ADC, a novel humanized anti-HER2 antibody conjugate, in NBST. Methods: This was an open-label, dose-escalation and expansion study in patients with HER2-overexpression (IHC 2+ and 3+) advanced solid cancers after failure of standard treatment. The dose escalation consisted of accelerated (0.1 and 0.5 mg/kg) and “3+3” titrations (1.0, 2.0, 2.5 and 3.0 mg/kg). In dose expansion stage, patients were given RC48-ADC at 2.0 mg/kg, Q2W. Results: As of Aug 20, 2019, 57 patients (including 47 with gastric cancer and 4 with urothelial cancer) were treated at 0.1 (1 patient), 0.5 (1 patient), 1.0 (3 patients), 2.0 (6 patients in dose escalation and 32 patients in dose expansion), 2.5 (11 patients), and 3.0 mg/kg (3 patients), respectively. Most of them were Stage IV (91.2%) or with metastasis (96.5%). DLT was observed in 1, 2, and 1 patient at 2.0, 2.5, and 3.0 mg/kg, respectively. The MTD was 2.5 mg/kg. Most commonly reported TRAEs were WBC count decreased (66.7%), fatigue (56.1%), neutrophil count decreased (54.4%) and hemoglobin decreased (52.6%). Grade 3/4 TRAEs were reported in 28 patients (49.1%). Confirmed ORR was 21.1% (8/38) for 2.0 mg/kg, and 17.5% (10/57) for all patients. DCR was 52.6% and 49.1%, respectively. PFS was 3.6 months (95% CI: 4.1, 11.3) for 2.0 mg/kg. Subgroup ORR was 20.7% (6/29) at 2.0 mg/kg and 18.2% (2/11) at 2.5 mg/kg for gastric cancer, and 50.0% (2/4) for urothelial cancer. Conclusions: RC48-ADC demonstrated a good safety profile and promising anti-tumor activity in the late stage solid tumor including gastric cancer and urothelial cancer. Response and PFS benefits were clinical meaningful at 2.0 mg/kg and 2.5 mg/kg. Phase 2 pivotal study (NCT03556345) in gastric cancer is ongoing. Clinical trial information: NCT02881190.
Per oral vitamin B12 replacement therapy after gastrectomy and its optimal dose (retrospective study) and our protocol of a prospective clinical trial.
Authors: Rino Yasushi , Aoyama Toru , Yukawa Norio , Cho Haruhiko , Oshima Takashi , Yamada Takanobu , Atsumi Yosuke , Hara Kentaro , Numata Masakatsu , Kazama Keisuke , Tamagawa Hiroshi , Sato Tsutomu , Yoshikawa Takaki 
Published: February 2020

338 Background: Postgastrectomy vitamin B12 deficiency is common metabolic sequel and worsens the quality of life of gastric cancer survivors. Recently, oral vitamin B12 replacement is reported. Therefore, we investigated retrospectively the efficacy of oral vitamin B12 replacement for gastric cancer patients with vitamin B12 deficiency after total gastrectomy. Methods: We reviewed 73 patients with gastric cancer who underwent total gastrectomy and were treated vitamin B12 replacement. Patients were consisted of 56 males and 17 females and median age was 70 y/o. We investigated initial treatment of vitamin B12 replacement and improvement of vitamin B12 deficiency. Results: Initial treatment of vitamin B12 replacements were intramuscular injection for 42 patients, per oral replacement for 28 patients and intravenous injection for 3 patients. Finally, all patients were treated with per oral replacement and the serum vitamin B12 levels became within normal range. Final vitamin B12 doses of replacement therapy were 500 µg of 20 out of 73 pts, respectively. Conclusions: Vitamin B12 replacement therapy should be necessary and continued. According to our results, one vitamin B12 tablet a day is enough. The vitamin B12 deficiency symptoms could be prevented. 500 micrograms vitamin B12 replacement orally is maybe effective and necessary. Our prospective clinical protocol (UMIN000030727): In this study, an oral vitamin B12 preparation (1500 μg/day, administered daily) was set as the control treatment, and a specific clinical trial was started to determine whether 500 μg/day daily administration would be sufficient for replacement therapy. Clinical trial information: UMIN000030727.
An economic evaluation of palliation of dysphagia in esophageal cancer: Analysis of the TROG 03.01/NCIC ES.2 phase III study in advanced esophageal cancer in patients treated with radiotherapy versus chemoradiotherapy.
Authors: Penniment Michael Gordon , De Ieso Paolo , Wong Rebecca , Afzali Hossein 
Published: February 2020

340 Background: In advanced oesophageal cancer (OC), 90% of patients have dysphagia as a principal symptom. The randomised TROG 03.01 trial reported no significant overall survival or dysphagia relief difference between 15 fractions (#) radiotherapy alone (RT) or RT plus chemotherapy (CRT) Future studies may consider RT hypofractionation, different chemotherapy, esophageal stenting, and best supportive care. Comparing costs and outcomes, economic evaluation often informs public funding decisions in countries such as Australia and the UK. The objective of this analysis was to derive baseline cost and outcome for further studies. Methods: Given equal outcomes (non-inferiority) between treatment arms, cost-minimisation analysis (CMA) was used to evaluate cost-effectiveness, cost a deciding factor if no other benefit was predicted. We explored 15 and 10 # courses used in TROG 03.01 and alternatives, 1 or 5 # Study design and uncertainty analyses were provided. Sub-analysis assessed salvage therapy for local and systemic progression. The EQ-5D (and SF-12) was used to determine utility values to estimate Quality-Adjusted Life years (QALYs) for evaluation. Results: From a health system perspective, costs and outcomes of RT were estimated at $4,700 AUD (15 # course). If, compared with RT alone, an alternative option is more costly but more effective, then a cost-utility analysis (CUA) is preferred economic evaluation. Intervention and in/outpatient costs, initial phase and post treatment were considered for stent insertion and alternative chemotherapy regimens. Alternatively, autocontoured CT planning and machine learning were modelled to reduce RT planning cost (est. $650/p). Total cost for 5 # is $3200 could be further reduced through process efficiency savings using CMA approach. Conclusions: The value of palliative approaches in common malignancies is difficult to assess. This study uses economic analysis to guide paying authority decisions. RT can be simplified from the TROG 03.01 approach to lessen cost and simplify treatment. The clinical efficiency of 1 or 5 # should be evaluated.
Perioperative docetaxel, oxaliplatin, and capecitabine (DOX) in resectable adenocarcinomas of lower esophagus, esophagogastric junction, and stomach.
Authors: Valame Shaunak , Panda Dipanjan , Zaidi Shuaib , Garg Praveen , Razvi Syed Asim , Singhal Manish Kumar , Das Pratap K. , Baweja Pankaj , Patowary Jayanta 
Published: February 2020

349 Background: In a real-world scenario, Fluorouracil-based triplet combination chemotherapies have limited feasibility with regards to toxicity, need for central venous access, and hospitalization. The primary objective of this study was to assess pathological tumor regression to Capecitabine-based triplet regimes, with the additional possible benefit of overcoming the aforementioned barriers. Methods: This Single-Arm, Prospective study investigated the primary outcome of histopathologic regression to perioperative Docetaxel, Oxaliplatin, and Capecitabine (DOX) combination regime in histologically confirmed resectable Esophageal, Esophagogastric Junction, and Gastric Adenocarcinomas. Three preoperative and 3 postoperative cycles of Docetaxel 60mg/m2 plus Oxaliplatin 100mg/m2 on Day 1, with Capecitabine 500mg/m2 twice daily from Day 1 to Day 21 were administered, with cycles repeating every 21 days. Histopathologic regression was assessed by Modified Ryan’s Schema on surgical specimen. The study had an 80% power (two-sided significance of 0.05) to detect a 20% pathological complete response. Secondary endpoints were Overall Survival, Progression-Free Survival, and Toxicity analysis. Results: Between June 2017 to May 2019, 28 patients (median age 54.5 years [Range 33 – 82]; Male 78.6%; ECOG PS 1/2 = 42.9%/57.1%) were enrolled in the study of which 92.9% completed preoperative chemotherapy. Of the 20 patients operated upon, 100% were R0 resections. Pathological complete response was observed in 20% (4/20). Ninety percent of the operated patients completed the postoperative treatment. The most common grade ≥3 toxicities were Palmar-Plantar Erythrodysesthesia (10.7%), Fatigue (10.7%), and Diarrhoea (7.1%). Conclusions: Perioperative DOX met its primary endpoint of 20% pathologic complete regression with a favourable toxicity profile and was feasible to administer in resectable Esophageal, Esophagogastric Junction, and Gastric Adenocarcinomas. This regimen deserves further evaluation in larger phase III trials.
Personalized ANtibodies for GastroEsophageal Adenocarcinoma (PANGEA): Primary efficacy analysis of the phase II platform trial (NCT02213289).
Authors: Catenacci Daniel V.T. , Lomnicki Samantha , Chase Leah , Peterson Bryan , Moore Kelly , Markevicius Ugne , Alpert Lindsay , Setia Namrata , Hart John , Liao Chih-Yi , Siddiqui Uzma , Turaga Kiran , Posner Mitchell C. , Kipping-Johnson Kristen , Narula Sunil , Rampurwala Murtuza M. , Ji Yuan , Karrison Theodore , Polite Blase N. , Kindler Hedy L. 
Published: February 2020

356 Background: 1-yr OS is ~40% for HER2- & ~55% for HER2+ advanced (aGEA). Targeted therapies (tx) have had limited benefit due to molecular heterogeneity. Methods: This phase 2a study of a personalized tx strategy (PTS) enrolled newly diagnosed aGEA pts who then received up to 3 cytotoxic (cx) lines: first line (1L) 5FU + oxaliplatin, 2L 5FU + irinotecan & 3L 5FU + docetaxel. Baseline biomarker profiling (BP) was mandated on primary & metastatic tumors (PT/MT) & progressive disease points (PD1, PD2). Assigned antibody (AN) was added to cx by a predefined prioritized tx algorithm (PTA) (Table) based on the MT BP. At PD1, pts went to 2L cx + initial AN. Upon results of PD1 BP, pts changed AN only if BP evolved per PTA. The same was done at PD2. If AN was unavailable (MET/FGFR2), these pts were tx’d with cx alone (not ITT). The 10 endpt was 1-yr OS of the PTS. Assuming historical 50% 1-yr OS for all aGEA pts, 68 pts tx’d per protocol PTS provided 80% power to detect an HR=0.67, corresponding to a 1-yr OS rate of 63% (under exponential survival), using a 1-sided test at the 0.10 alpha level. 20 endpts: safety, feasibility, PT/MT BP discordance at baseline & over tx line, & OS/PFS/ORR by tx line & BP group. Results: Between 6/2015-5/2019, 80 consecutive pts enrolled at 3 sites: ECOG PS 0-2 40/33/7; Male 80%; median age 60, range 28-81, peritoneal disease 36%. AN assigned by PTA at 1L & 1-yr OS are shown (Table). PT/MT discordance was 37%. Of 68 pts treated by PTS ITT, the 1-yr OS was 69.4% (p<0.001). The mOS was 16.4m [95%CI 13.8-20.8]. Any grade >3 tox thru all 3 tx lines was seen in 32% of pts. 20 analyses will be presented. Conclusions: PANGEA was feasible & met its 10 efficacy objective with observed 1-yr OS of 69.4%, meriting a randomized study. Clinical trial information: NCT02213289 . U.S. National Institutes of Health.[Table: see text]