bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of additional treatment after endoscopic submucosal dissection for esophageal squamous cell carcinoma in real-world clinical practice.
Authors: Sakaguchi Nanako , Yamaguchi Toshifumi , Ishizuka Yasunobu , Kodama Hiroyuki , Miyamoto Takahiro , Terazawa Tetsuji , Kojima Yuichi , Kii Takayuki , Sanomura Makoto , Goto Masahiro , Higuchi Kazuhide 
Published: February 2020

305 Background: Endoscopic submucosal dissection (ESD) is the standard therapy for the T1a- EP/LPM esophageal squamous cell carcinoma (ESCC), although it is difficult to diagnose the invasion depth accurately before ESD. The incidence of lymph node metastases in ESCC involving the muscularis mucosae (pT1a-MM) and the submucosa (pT1b-SM) is reported to range from approximately 10% to 30%. For the patients with MM, SM or involving LVI or positive vertical margin after ESD, additional treatment (AT) is recommended to prevent local recurrence. However, the AT is not always performed to the frail or elderly patients. The aim of this study is to investigate the outcome of AT and non-AT (NAT) after ESD for ESCC in the real-world clinical practice. Methods: We retrospectively reviewed the ESCC patients who were pathologically confirmed T1a-MM or T1b-SM (UICC-TNM7th) after ESD at Osaka medical college hospital between 2004 and 2016. Results: Among 224 patients who received ESD, 52 patients were pT1a-MM (n = 36; 69.2%) or pT1b-SM (n = 16; 30.8%).Twelve of 52 patients (23%) received AT and forty patients (77%) received NAT. Six patients (AT group: 2 patients, NAT group: 4 patients) had local lymph node recurrence. Five of them underwent salvage therapy. Median follow up time were 54.3 months (range: 48.4-62.4). The 3-, 5-year RFS rate and the 3-, 5-year OS rate were 83.8%[95%CI: 68.2- 92.6], 73.4% [95%CI: 56.0- 85.7] and 94.7% [95%CI: 81.3- 98.6], 91.7% [95%CI: 77.1- 97.3] in all patients, respectively. The 5-year RFS and OS rate were 77.8%, 90.0% in the AT group and 71.6, 92.2% in the NAT group. Conclusions: Although the AT tended to prevent local recurrence, the OS was comparable with NAT because of salvage therapy. The active surveillance is recommended for T1a-MM or T1b-SM ESCC.
Treatment patterns and long-term clinical outcomes in Chinese patients with nonmetastatic gastric cancer: Results from the non-interventional EVIDENCE registry study.
Authors: Ji Jiafu , Qin Shukui , Wang Xin , Zhou Weiping , Chen Lin , Zheng Zhichao , Su Wuyun , Zhang Helong , Wang Jianhua , Luo Qi , Tang Yong , Shen Lin 
Published: February 2020

307 Background: Although gastric cancer (GC) is a leading cause of cancer-related death in China, important questions about optimal management remain unanswered. The EVIDENCE registry study evaluated data from patients with GC in China to assess the pattern of treatments and long-term clinical outcomes. Methods: Five cohorts of patients with different HER2 and metastatic (m) status were evaluated from April 2013 to June 2018 in this prospective, multicenter, non-interventional, real-world study. Data from patients with operable non-mGC are reported: Cohort III (HER2+) and Cohort V (HER2−). Outcome measures included overall survival (OS), event-free survival (EFS), and disease-free survival (DFS). Results: Cohorts III/V included 758 patients (Cohort III, 271; Cohort V, 487); 75.5% were male and the mean age was 58.8 years. The majority of Cohort III/V patients (538/758; 71.0%) received only adjuvant treatment, with 215/758 (28.4%) receiving S1+oxaliplatin. Neoadjuvant or adjuvant trastuzumab was administered to 43/758 patients (Cohort III, 42; Cohort V, 1). Radiation during neoadjuvant or adjuvant treatment was administered to 23/758 (3.0%) patients. The median duration of follow-up was 515 days, during which 72 (9.5%) patients died due to progressive disease. OS rates (95% CI) for Cohorts III and V were 94% (89–96) and 95% (92–97) at 1 year, and 76% (67–83) and 70% (64–75) at 3 years, respectively. Respective EFS rates were 82% (76–87) and 86% (83–89) at 1 year, and 62% (53–70) and 57% (51–63) at 3 years; and respective DFS rates were 88% (82–93) and 86% (81–89) at 1 year and 69% (58–78) and 62% (55–68) at 3 years. Multivariate analysis indicated that the primary tumor site (p = 0.004) and overall cancer stage (p < 0.001) were associated with DFS. Regarding the primary tumor site, there was a trend towards better DFS for antrum tumors (hazard ratio 0.59; 95% CI 0.32–1.07) when evaluated against gastroesophageal junction tumors. Conclusions: This longitudinal analysis of clinicopathologic characteristics and outcomes of Chinese patients with non-mGC will provide critical information that will help to inform disease management. Clinical trial information: NCT01839500.
Association of real-world agreement between HER2 expression and ERBB2 amplification with trastuzumab therapy benefit in advanced gastric/esophageal (adv GE) cancer patients (pts).
Authors: Stein Stacey , Snider Jeremy , McCusker Margaret Elizabeth , Miksad Rebecca A. , Alexander Brian Michael , Castellanos Emily , Backenroth Daniel , Schrock Alexa Betzig , Madison Russell , Carson Kenneth Robert , Ali Siraj Mahamed 
Published: February 2020

310 Background: Trastuzumab (T) plus chemotherapy is standard of care for pts with HER2+ adv GE cancer. Selection for T relies on HER2+ result by immunohistochemistry (IHC) +/- in-situ hybridization (ISH); ERBB2 amplification by comprehensive genomic profiling (CGP) also predicts benefit. As CGP use increases, it is important to explore associations of IHC/ISH and CGP result agreement with clinical outcomes in pts with adv GE cancer. Methods: Pts with adv GE cancer were selected from the Flatiron Health-Foundation Medicine (FMI) clinico-genomic database (CGDB), a nationwide de-identified EHR-derived clinical database linked to FMI genomic data. Pts treated from 01/2011-12/2018 with CGP data for tissue specimens collected before 1L were included. Agreement between HER2 status by IHC +/- ISH v ERBB2 amplification by CGP was assessed. For 1L containing T, time to tx discontinuation (TTD) and overall survival (OS) from 1L start stratified by HER2:ERBB2 agreement and ERBB2 copy number (CN) [ERBB2+ = CN >4] were estimated with unadjusted Kaplan-Meier analysis and adjusted (practice type, sex, age at adv dx) hazard ratios (aHR) from Cox proportional hazards models. Results: Of 596 HER2-tested pts with adv GE cancer in CGDB, 174 (29%) were HER2+ by IHC/ISH. Median age at adv dx was 63 y; 76.5% were male and 97% had adenocarcinoma. Overall HER2:ERBB2 agreement was 91%. Of 123 HER2+ 1L T-treated pts, median TTD and OS were longer for HER2+:ERBB2+ (concordant; n = 93) v HER2+:ERBB2- pts (discordant; n = 30): TTD, 5.2 v 0.8 months, aHR 0.46 (0.29-0.70); OS 14.8 v 7.5 months, aHR 0.38 (0.21-0.68). Median OS was 22.0 vs 8.4 months for 1L T-treated pts with ERBB2 CN > 30 (median) v CN ≤30 (aHR 0.69 [0.37-1.27]). Conclusions: In this large real-world clinico-genomic dataset, HER2:ERBB2 agreement was high in tested pts with adv GE cancer. 1L T-treated pts with discordant tests (HER2+:ERBB2-) had significantly shorter TTD and OS. Pts with higher ERBB2 CN had longer OS, but this finding was not significant after adjusting for covariates. Further research is needed to explore associations between HER2:ERBB2 agreement and clinical outcomes in this population.
Retrospective comparison of neoadjuvant chemoradiation (nCRT) +/- surgery using the CROSS trial regimen and definitive chemoradiation (dCRT) with carboplatin (C) and paclitaxel (P) in esophageal (EC), and gastroesophageal junction cancer (GEJC) in Canada.
Authors: Khalid Sidra , Hopman Wilma M. , Virik Kiran 
Published: February 2020

313 Background: Trimodality therapy using the CROSS trial protocol is an accepted standard of care for locally advanced EC and GEJC. For medically inoperable patients (pts), CRT has been a standard. CRT with C and P is an option in the definitive setting. This single institution review aims to assess the application and outcomes of the CROSS trial protocol in our real world population. Methods: From June 2012 until June 2018, a retrospective review was undertaken of 83 pts who underwent CRT with C and P with trimodaility or upfront definitive intent. 65 pts underwent nCRT; 40 proceeded to surgery. 18 had upfront dCRT. Pt demographics, clinical, pathological, treatment and surgical characteristics were assessed. These factors and outcomes were analyzed in exploratory analyses. Results: Of the 83 pts: median (m) age was 69 yrs (range 48-82), 34% were ≥ 75 yrs, 80% were male, 21% had CAD, 43% GERD, 23% Barrett’s, 77% adenocarcinoma, m tumor length was 5 cm, 36% had BMI > 30 and 80% were Siewert I tumors. The m RT dose was 50.4 Gy, m chemo doses were 5, m time to CRT was 69 days and m time from CRT to surgery was 66 days. 23% nCRT pts and 72% dCRT pts were ≥ 75 yrs and 49% and 33% of these respectively had no interruptions to CRT. Pts who underwent surgery were younger (p = 0.04) and weighed more (p = 0.05). Pts ≥75 yrs were likely to have dCRT (p = 0.001). For nCRT and surgery, nCRT only and dCRT respectively, median overall survival (mOS) was 35.5, 12.1 and 17.1 months (M) (log rank p = 0.08), PFS was 32.2, 10 and 9.6M (log rank p = 0.01). Compared to the other 2 groups, pts who underwent surgery had: no COPD (p = 0.004), less CAD (p = 0.003), less renal impairment (p = 0.023) and had lower esophageal tumors (p = 0.027). mOS for pts who had nCRT was 28.9M and 17.1M for dCRT (log rank p = 0.70). Further correlative outcome data will be presented. Conclusions: Despite the broadening of CROSS trial eligibility criteria in our real world data, there appears to be a survival benefit with trimodality therapy. The use of C and P in dCRT may be of value especially in the elderly, and requires further study.
Patterns of disease, treatment, and outcomes of esophageal cancer arising within a previous radiation treatment field.
Authors: Ma Lucy Xiaolu , Sun Peiran , Espin-Garcia Osvaldo , Suzuki Chihiro , Jiang Di Maria , Lim Charles Henry , Taylor Kirsty , Chan Bryan Anthony , Sim Hao-Wen , Natori Akina , Chen Eric Xueyu , Liu Geoffrey , Knox Jennifer J. , Yeung Jonathan , Darling Gail Elizabeth , Kim John , Kalimuthu Sangeetha , Elimova Elena , Jang Raymond Woo-Jun 
Published: February 2020

328 Background: Esophageal cancer arising within a previous radiation treatment field (ECRF) is rare. The patterns of disease, treatment and outcomes in these patients (pts) have not been well characterized. Methods: A retrospective analysis was performed for pts treated for esophageal cancer at the Princess Margaret Cancer Centre from 2002-2016. Electronic medical records of all pts with a histologic diagnosis of esophageal cancer occurring within the field of previous radiotherapy were reviewed. The Kaplan-Meier method was used to calculate progression free survival (PFS) and overall survival (OS). Results: Of 31 ECRF pts identified, the most common prior cancer was head and neck (45%), median radiation (RT) dose 50Gy, median time to diagnosis of esophageal cancer 12 years. Features at diagnosis of ECRF included: median age 71 years, 58% male, 87% with performance status (PS) 0-1, 77% squamous cell carcinoma, 19% stage IV. Treatment intent was curative in 16 pts, palliative in 15 (Table). Reasons for palliative treatment were: 40% metastatic, 53% comorbidities/PS, 7% anatomic factors. Of resected pts, 36% had a pT1-2 tumour, 55% pN0, 69% R0. For curative pts, median PFS was 26.2 months (95%CI 10.9-34.4) with a 3 year PFS rate of 35% (95% CI 15-81). Median OS for curative pts was 26.4 months (95%CI 17.8-105.5) with a 3 year OS rate of 43% (95% CI 22-83). Most palliative pts were unable to have chemotherapy due to comorbidities and PS. Median OS for palliative pts was 9.5 months (95% CI 3.6-15.4). Conclusions: Most ECRF pts presented with earlier stage disease; however, more than a third of these could not have aggressive curative treatment due to comorbidities and/or PS. Most curative pts had surgery alone. Few palliative pts had chemotherapy, largely due to poor clinical status. Our data suggest that outcomes in both curative and palliative ECRF pts may be limited by the ability to tolerate standard of care treatments. [Table: see text]
Multiple primary cancers in patients with gastric cancer: A retrospective study in China National Cancer Center.
Authors: Lei Qi , Zhang Runfeng , Zou Xi , Zhou Aiping , Du Chun-Xia 
Published: February 2020

337 Background: Gastric cancer (GC) is common in China. With the total incidence of cancer keeping rising in China, the occurrence of multiple primary cancers with GC is growing. Early detection and diagnosis of second or more primary cancers are vital for patients’ survival. Methods: Patients with multiple primary cancers containing gastric adenocarcinoma treated in China National Cancer Center from January 2010 to December 2017 were included. A 6-month interval was used to separate synchronous and metachronous cancers (according to IARC/IACR criteria). Results: 479 patients met the criteria were included, with 452 (94.4%), 24 (5.0%), 3 (0.6%) patients having two, three or more primary cancer sites respectively, contributing a total of 510 cancer sites besides stomach (Table). Malignancies at 257 (50.4%) sites occurred with GC synchronously, while 253 (49.6%) occurred metachronously. The median age at the diagnosis of first cancer was 59 (interquartile range [IQR], 53-66) years. The median interval between the diagnosis of first primary cancer and metachronous second one was 50.3 (IQR, 23.7-97.0) months. Cancers outside gastrointestinal (GI) tract were more likely to occur with GC metachronously, while GI tract cancers were more likely to occur synchronously (χ²=55.36, p<0.001). Out of 479 patients, there were 352 (73.6%) male and 127 (26.4%) female. The most common associated cancer was esophagus cancer (142, 40.3%) in male, and breast cancer (31, 25.4%) in female. 236 (49.8%) patients were current smokers or ex-smokers, and 190 (40.1%) were regular alcohol consumers. 110 (23.2%) had first-degree relative cancer family history, with 84 (17.7%) having GI tract cancer family history. Conclusions: GI tract including esophagus and colorectum should be carefully scrutinized during GC peri-operation period. Further genetic research is warranted to explore the potential pathogenesis of multiple primary cancers.[Table: see text]
Economic impacts of care by high-volume providers for noncurative esophagogastric cancer: A population-based analysis.
Authors: Hallet Julie , Look Hong Nicole , Zuk Victoria , Davis Laura , Gupta Vaibhav , Earle Craig , Mittmann Nicole , Coburn Natalie 
Published: February 2020

339 Background: Esophagogastric cancer (EGC) is one of the deadliest and costliest malignancies to treat. Care by high-volume providers can provide better outcomes for patients with EGC. Cost implications of volume-based cancer care are unclear. We examined the cost-effectiveness of care by high-volume medical oncology providers for non-curative management of EGC. Methods: We conducted a population-based cohort study of non-curative EGC over 2005-2017 by linking administrative healthcare datasets. High-volume was defined as >11 patients/provider/year. Healthcare costs ($USD/patient/month-survived) were computed from diagnosis to death or end of follow-up from the perspective of the healthcare system using validated costing algorithms. Multivariable quantile regression examined the association between care by high-volume providers and costs. Sensitivity analyses were conducted by varying costing horizons and high-volume definitions. Results: Among 7,011 non-curative EGC patients, median overall survival was superior with care by high-volume providers with 7.0 (IQR: 3.3-13.3) compared to 5.9 (IQR: 2.6-12.1) months (p < 0.001) for low-volume providers. Median costs/patient/month-lived were lower for high-volume providers ($5,518 vs. $5,911; p < 0.001), owing to lower inpatient acute care costs, despite higher medication-associated and radiotherapy costs. Care by high-volume providers was independently associated with a reduction of $599 per patient/month-lived (95% confidence interval: -966 to -331) compared to low-volume providers. The incremental cost-effectiveness ratio was -393. Care by high-volume providers remained the dominant strategy when varying the high-volume definition and the costing time horizon. Conclusions: Care by high-volume providers for non-curative EGC is associated with superior survival and lower healthcare costs, indicating a dominant strategy that may provide an opportunity to improve cost-effectiveness of care delivery.
A phase II trial of low-dose nab-paclitaxel for patients with previously treated or recurrent advanced gastric cancer (OGSG1302).
Authors: Hirota Masashi , Tamura Shigeyuki , Taniguchi Hirokazu , Takeno Atsushi , Imamura Hiroshi , Fujita Junya , Matsuyama Jin , Kimura Yutaka , Kawada Junji , Hirao Motohiro , Nishikawa Kazuhiro , Fujitani Kazumasa , Kurokawa Yukinori , Sakai Daisuke , Kawakami Hisato , Shimokawa Toshio , Satoh Taroh 
Published: February 2020

350 Background: Paclitaxel is a key drug in second-line chemotherapy for advanced or recurrent gastric cancer (AGC) and nanoparticle albumin-bound paclitaxel (nab-PTX) is also widely used in Japan. A previous phase II trial in Japan showed the effectiveness of nab-PTX (260 mg/m2) administered every 3 weeks (q3w) in patients with AGC with a response rate (RR) of 27.8%; however, toxicity was major concern with grade ≥3 neutropenia (49.1%) and peripheral neuropathy (23.6%). To solve this problem, we investigated the efficacy and safety of low-dose q3w nab-PTX regimen in AGC. Methods: Eligibility requirements included: aged ≥20 years, HER2-negative, histologically confirmed, unresectable or recurrent gastric adenocarcinoma, one or more prior chemotherapy containing fluoropyrimidine regimens, presence of measurable lesion(s) according to RECIST ver. 1.1, ECOG PS of 0–2, and adequate organ function. Nab-PTX was administered at a dose of 220 mg/m2 every 3 weeks. The primary endpoint was the RR. Secondary endpoints were overall survival (OS), progression-free survival (PFS), disease-control rate (DCR), incidence of adverse events, relative dose intensity and proportion of patients who received subsequent chemotherapy. Results: Thirty-three patients were enrolled from 10 institutions in Japan. Of the 32 patients treated with protocol therapy, RR (CR, PR) was 3.1% (95% CI, 0–16.2%), which was not reached the protocol-specified threshold (p = 0.966). DCR (CR, PR, SD) was 37.5% (95% CI, 21.1–56.3%), median OS and PFS were 6.3 months (95% CI, 4.4–14.2) and 2.2 months (95% CI, 1.8-3.1). Relative dose intensity was 97.8% (215 mg/m2). 62.5% of patients received subsequent chemotherapy. Most common grade ≥3 adverse events were neutropenia (38%), anemia (13%), fatigue (19%), anorexia (16%), and peripheral neuropathy (13%). Conclusions: Low-dose regimen of q3w nab-PTX was slightly less toxic, although it did not demonstrate the same effect as the original regimen in response rate. Therefore, it is not recommended for AGC in second or later line setting. Clinical trial information: UMIN 000012701.
Survival benefit of conversion therapy after intensive chemotherapy for unresectable metastatic gastric cancer: A propensity score-matched analysis.
Authors: Ohnuma Hiroyuki , Sato Yasushi , Omori Ginji , Onoyama Naoki , Ameda Saki , Ito Ryo , Hamaguchi Kota , Hayasaka Naotaka , Sato Masanori , Murase Kazuyuki , Takada Kohichi , Miyanishi Koji , Ito Tatsuya , Nobuoka Takayuki , Takemasa Ichiro , Kato Junji 
Published: February 2020

354 Background: The significance of conversion therapy (CT), whereby patients (pts) with unresectable disease respond to chemotherapy and subsequently receive surgery with curative intent (adjuvant surgery: AS), has been specifically established for metastatic colorectal cancer. However, such a strategy for advanced or recurrent gastric cancer (AGC) remains controversial. This study aims to clarify the clinical significance of CT for AGC. Methods: In this retrospective multi-institution observational study, we analyzed 168 AGC pts who received chemotherapy consisting of docetaxel, cisplatin or oxaliplatin, and S-1 ± trastuzumab between 2003 and 2019. We divided pts into two groups: those who underwent CT (group CT) or chemotherapy only (group C). Propensity score analysis with 1:1 matching minimized confounding bias when comparing efficacy and safety between groups. Results: A tumor response to chemotherapy was observed in 82.4% of all cases, while 34.5% (58/168) underwent AS. Fifty-one of the 58 pts underwent an R0 resection, and 79.3% were deemed histological responders. After matching, 44 pairs of C and CT pts were selected; significant differences in baseline characteristics were not observed. Incidences of adverse events during chemotherapy were similar between groups, with neutropenia and febrile neutropenia as common grade 3–4 events. Compared with group C, group CT had a significantly better median overall survival (OS) (15.5 vs. 46.0 months; hazard ratio [HR] 0.32; 95% confidence interval [CI] 0.18–0.58; p < .001), and a prolonged progression-free survival (6.5 vs.22.6 months; HR 0.33; 95% CI 0.19–0.56; p < .001). Subgroup analysis of OS showed a favorable trend for CT for almost all parameters. In a multivariate analysis, ECOG performance status (HR 0.10; 95% CI 0.03–0.31) and AS (HR 0.20; 95% CI 0.10–0.40) correlated with favorable OS. In the CT group, pathological response was an independent prognostic factor (HR 0.16; 95% CI 0.06–0.39). Conclusions: CT was associated with better outcomes in AGC pts, even after baseline adjustment. Our data warrants further large-scale studies to establish a conversion therapeutic strategy.
Chemotherapy-induced neutropenia with FOLFOX in the adjuvant treatment of colorectal cancer.
Authors: Gotfrit Joanna , Marginean Horia , Maroun Jean Alfred , Trincao-Batra Sara , Asmis Timothy R. , Vickers Michael M. , Goodwin Rachel Anne 
Published: February 2020

38 Background: Patients undergoing adjuvant treatment with FOLFOX for colorectal cancer (CRC) are at risk of developing chemotherapy-induced neutropenia (CIN). We assessed the risk of CIN and the use of granulocyte colony stimulating factor (GCSF). Methods: We performed a retrospective chart review of patients with CRC treated with FOLFOX at our institution from 2013 - 2015. Demographic and treatment data were collected. CIN was defined as ANC <1.5, and all episodes of neutropenia were assumed to be the result of chemotherapy. Results: A total of 302 patients were included (baseline demographics in Table). In the overall cohort, 174 (58%) of patients had at least 1 episode of CIN. The risk CIN was 47% in stage II, 60% in low risk stage III (T1-3 and N1), and 58% in high risk stage III (T4 or N2). Among patients with at least 1 episode of CIN, the 1st CIN event occurred during the 1st 3 months of treatment in 76%, and the median cycle of 1st occurrence was 4 (95% CI 4-5), which did not differ by stage. Among patients who had at least 1 episode of CIN, 112 (64%) had a 2nd episode at a median cycle of 9 (95% CI 8-10). Among patients with at least 1 episode of CIN, 79 (45%) received subsequent GCSF, initiated 1 cycle after the 1st CIN event 37% of the time. Among patients with at least 2 episodes of CIN (n=112), 58 (52%) received GCSF after the 1st or 2nd event. Of these, 40 patients (69%) started GCSF newly after the 2nd CIN event. Among patients starting GCSF after the 2nd CIN event, 47% initiated GCSF 1 cycle later. The median cycle at which the relative dose intensity of FOLFOX decreased to <85% was cycle 6 (95% CI 5-8) in those with no CIN events, cycle 3 (95% CI 2-4) in those with at least 1 CIN event treated with GCSF, and cycle 5 (95% CI 4-6) in those with at least 1 CIN event treated without GCSF. Conclusions: CIN is a frequent occurrence during the adjuvant treatment of CRC with FOLFOX and most often occurs in the first 3 months of treatment. While oncologists may treat some patients with 3 months of FOLFOX rather than 6, physicians must be aware of CIN regardless of the planned duration of treatment. Early initiation of GCSF may be a consideration. [Table: see text]