bluuebunny/crossref_metadata_2025_split huggingface dataset:
A National Cancer Database (NCDB) analysis of the impact of nonmetastatic colon cancer sidedness on survival.
Authors: Patel Deven , DiPeri Timothy , Cox Brian , Hendifar Andrew Eugene , Osipov Arsen , Cho May Thet , Fakih Marwan , Gong Jun , Gangi Alexandra 
Published: January 2021

139 Background: Differences in embryological origin and tumor biology distinguish right-sided colon cancer (RCC) from left-sided colon cancer (LCC). Previous studies characterizing the prognostic impact of colon cancer laterality on clinical outcomes in non-metastatic colon cancer have been conflicting, thus closer examination is needed. Methods: Using the NCDB, patients with stage I-III colon cancer between 2004-2014 were stratified according to tumor location; RCC vs. LCC. Patient (pt) and tumor characteristics were compared in univariate analysis, survival (OS) was estimated by Kaplan-Meier (KM) curves and Cox proportional hazards modeling. Binomial logistic regression analysis was utilized to identify variables associated with colon cancer laterality. Results: Of the 342,735 pts who met inclusion criteria, 210,343 (61.4%) were diagnosed with RCC, and 132,392 (38.6%) with LCC. Pts with RCC were older (mean 71.6 vs. 66.4 years, p< 0.001) and predominantly female (65% vs. 35%, p< 0.001) compared to those with LCC. A trend towards poorer OS was seen in pts with RCC (mean 91.0 mos [95% CI: 90.2-91.8]) compared to LCC (112.2 mos [95% CI: 110.9-113.6]) in unadjusted analysis. On Cox multivariable adjusted analyses there was a significant but minimal impact on OS and laterality (hazard ratio or HR [LCC as ref] 0.978, 95% CI 0.967-0.989 p< 0.0001). Multiple unadjusted KM survival analyses showed RCC with T4 disease, high-grade, LVI/PNI, positive margins, N0-N2 disease, tumor deposits, and receipt of adjuvant chemotherapy had poorer OS than those features in LCC (all p < 0.0001). Binomial logistic regression showed RCCs were significantly more likely to be higher grade (odds ratio or OR 2.024) and MSI-H (OR 2.010) with trends (nonsignificant) towards more likely having N1-2 positive disease, LVI, less receipt of adjuvant chemotherapy, and fewer tumor deposits. Conclusions: The impact of sidedness on prognosis in stage I-III colon cancer is complex. In this large, population-based study, RCC tends to be associated with more adverse prognostic features than LCC. More investigation into the biologic differences between RCC and LCC is warranted and how they impact phenotype and survival.
Real-world outcomes of esophagectomy versus chemoradiotherapy for clinical stage I esophageal squamous cell carcinoma.
Authors: Yukami Hiroki , Sawada Kentaro , Fujiwara Hisashi , Mishima Saori , Kotani Daisuke , Kadota Tomohiro , Inaba Atsushi , Nishihara Keiichiro , Sato Daiki , Nakajo Keiichiro , Yoda Yusuke , Nakamura Masaki , Hojo Hidehiro , Yano Tomonori , Fujita Takeo , Kojima Takashi 
Published: January 2021

178 Background: Recently, JCOG0502 trial have shown a comparable efficacy with chemoradiotherapy (CRT) and esophagectomy as standard treatment in patients with clinical stage (cStage) I esophageal squamous cell carcinoma (ESCC), showing the standard treatment option of CRT. However, there is few reports for comparison of clinical outcomes with these treatments in real-world. The aim of this study was to clarify the real-world outcomes in cStage I ESCC who performed with CRT or esophagectomy. Methods: This retrospective study included patients with clinical stage I ESCC who received thoracoscopic or open esophagectomy with three-field lymph node dissection or CRT mainly consisted of 5-fluorouracil and platinum with concurrent radiotherapy (50.4 Gy/28Fr or 60 Gy/30Fr) between 2009 and 2017 at National Cancer Center Hospital East. Survival outcomes were calculated using the Kaplan-Meier method, and the differences were evaluated using the log-rank test. Results: Among a total of 156 patients, 128 were male and median age was 68 years old. 120 and 36 patients underwent esophagectomy and CRT, respectively. ECOG performance status 0/1/2 were 138/12/6 patients. Tumor location was Ut/Mt/Lt in 16/87/53 patients. Clinical tumor depth (MM-SM1/SM2-SM3) were 33/123 patients. Patients’ characteristics were similar among treatment groups, except clinical tumor depth (SM2-3; 84.2% in esophagectomy group vs. 61.1% in CRT group, p = 0.005). All patients underwent radical surgery in esophagectomy group, while three patients (8.3%) in CRT group were received additional esophagectomy or endoscopic resection due to residual disease. With a median follow-up of 72 months, 5-year overall survival (OS) and progression-free survival rate were 81.5%/77.0% in esophagectomy group and 82.6/74.4% in CRT group (p = 0.89 and p = 0.48). In safety profile, grade 3 or higher stenosis was observed in 21.7% of esophagectomy group. There was no treatment-related death in both groups. In subgroup analysis for OS, elderly patients (75 years and older) tended to have better 5-year OS rate in CRT group (76.9% in esophagectomy group vs. 81.8% in CRT group), while younger patients ( < 75 years) showed comparable 5-year OS rate in both groups (82.4% in esophagectomy group vs. 82.9% in CRT group). Conclusions: Real-world data reproduced the results of clinical trial, supporting CRT as one of the standard treatment options in patients with cStage I ESCC.
Retrospective study of nivolumab monotherapy for advanced esophageal squamous cell carcinoma.
Authors: Mikuni Hayato , Yamamoto Shun , Oshima Kotoe , Hirano Hidekazu , Okita Natsuko , Shoji Hirokazu , Honma Yoshitaka , Iwasa Satoru , Takashima Atsuo , Boku Narikazu , Kato Ken 
Published: January 2021

179 Background: Based on the results of the ATTRACTION-1 and ATTRACTION-3 trials, nivolumab monotherapy has used for the treatment of metastatic or recurrence esophageal cancer patients who were refractory or intolerant to fluoropyrimidine and platinum since February 2020 in Japan. However, the ATTRACTION-1 trial mainly included patients who received nivolumab monotherapy as third or later-line treatments, which was different from the ATTRACTION-3 trial which mainly included patients as second-line treatment. Therefore, it is still unclear whether the treatment lines affect the efficacy of nivolumab in clinical practice. Methods: Medical records were retrospectively reviewed for patients diagnosed with metastatic or recurrence esophageal squamous cell carcinoma (ESCC) who received nivolumab monotherapy as second- or third or later-line treatments in our hospital. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) based on the RECIST ver1.1, and the incidences of adverse events (AEs) based on the CTCAE ver5.0. Results: Sixty-two patients were identified as the subject of this study. Thirty patients received nivolumab as second-line treatment (48.4%) and 32 patients as third or later-line treatments (51.6%). The median age (range) were 67 (33-80)/61 (52-84), PS 0 were 40.0/21.9%, prior taxane treatment rate were 6.7/93.8%, respectively. The ORR/DCR were 22.7/45.5% in second-line treatment, and 24.1/44.8% in third or later-line treatments (p=1.00). The median PFS (95% CI) was 2.3 (1.4-6.2)/2.3 (1.2-3.6) months in the second-/third or later-line treatments (HR=0.86, p=0.58). AEs of grade 3 or higher were observed in 6.7/6.3% of the second-/third or later-line treatments. Conclusions: There was no clear difference between second -line and third or later-line treatments in the short-term efficacy of nivolumab monotherapy in advanced ESCC patients.
Racial disparity in KRAS mutation frequency and outcomes in colorectal cancer (CRC): A U.S. population based study.
Authors: Bien Jeffrey , Aljehani Mayada , Lee Jerry S.H. , Lin Albert Y. 
Published: January 2021

18 Background: Racial disparity in CRC survival outcome is well documented. Although the reasons for disparity are unclear, a combination of differences in access to care, quality of care, differential treatment response, and underlying cancer biology are implicated. Further, recent studies have observed differences in KRAS mutation frequency between race/ethnic groups. KRAS mutation in metastatic CRC portends a worse response to EGFR-directed therapy, and predicts a poorer prognosis. In this study, we examined whether racial/ethnic differences in KRAS mutation frequency might impact CRC outcomes on a population-based level. Methods: We examined data from 202,237 CRC patients in the Surveillance, Epidemiology, and End Results (SEER) registry between 2010 and 2015. The differences in tumor mutation status by stage and race/ethnicity were examined by χ2 testing. Cause-specific survival (CSS) and overall survival by mutation status were plotted by Kaplan-Meir curves. A multivariable Cox-proportional hazards model was used to construct hazard ratios and 95% confidence intervals (CI) using patient demographics, tumor characteristics, and KRAS mutation status. Results: Overall, about 9% of patients (n = 18,248) in the SEER registry had KRAS status available. In this cohort, tumors from Non-Hispanic Black (NHB) (48%) or Hispanic patients (44%) carried a greater KRAS mutation (mKRAS) rate when compared against Non-Hispanic White (NHW) (39%) or Asian or Pacific Islander (API) patients (37%) (p < 0.01). The assessment of the impact of mKRAS within each race/ethnic group, comparing patients with mKRAS versus wild-type KRAS (wKRAS) on CSS risk show a 7% risk increase for NHW, (HR = 1.07; 95%CI:1.02-1.12), a 15% risk increase for NHB, (HR = 1.15; 95%CI:1.04-1.26) and no significant increase among API, (HR = 1.02; 95%CI:0.92-1.4). Among patients with wKRAS, with NHW for reference, the risk of CSS is 11% higher among NHB (HR = 1.11; 95%CI:1.00-1.23), 14% higher for Hispanic, (HR = 1.14; 95%CI:1.02-1.26) and no significant difference observed among API, (HR = 1.03; 95%CI:0.91-1.16). Evaluation of the interaction between race/ethnicity and KRAS status on the CSS risk shows an increase of: 11% for mKRAS NHW, (HR = 1.11; 95%CI:1.00-1.23), 13% risk for NHB (HR = 1.13; 95%CI:1.01-1.25), 11% for Hispanic wKRAS, (HR = 1.11; 95%CI:1.04-1.18), 31% for Hispanic mKRAS (HR = 1.31; 95%CI:1.18-1.145), 16% for wKRAS API (HR = 1.16; 95%CI:1.03-1.29). In contrast, no significant difference in risk is seen for NHB nor API patients, HR = 1.02 (95%CI:0.90-1.14) and 1.04 (95%CI:0.91-1.20) respectively. Conclusions: mKRAS, compared to wKRAS, connotes worse CSS among NHW and NHB patients. Among wKRAS, NHB and Hispanic patients still experience higher mortality risk. This data suggests the negative prognosis heretofore associated with mKRAS may be linked to race/ethnicity and worthy of further study.
Treatment patterns, healthcare resource use, economic, and survival outcomes associated with nonresectable advanced esophageal cancers in Taiwan.
Authors: Tsai Yiling , Chang Chee Jen , Navaratnam Prakash , Friedman Howard Steven , Xiao Hong , Gricar Joseph 
Published: January 2021

180 Background: In Taiwan, limited real-world data indicate that initial EC diagnosis tends to occur at an advanced stage with limited therapeutic options and poor prognosis. Methods: This was a retrospective ‘real world’ observational study using the Taiwan National Health Insurance Research Database (NHIRD). Patients having at least one hospital record with a primary ICD-9 or ICD-10 code of EC were selected from Jan 1st, 2013 through Dec 31st, 2018. The first date of EC diagnosis was defined as the index date. Patients were followed for a minimum ± 30 days from the index date and were stratified by staging, clinical presentation (i.e. resectable vs. non-resectable advanced) and tumor histotype (squamous cell carcinoma, adenocarcinoma, unknown). Key characteristics such as demographics, clinical parameters, medication utilization, health care resource utilization, costs incurred, and survival were tracked for the overall population, resectable and non-resectable, advanced cohorts. Results: Patients identified with non-resectable advanced EC (N = 4,340) had a mean (SD) age of 59.7 (12.3) years and the vast majority were male (n = 4,044, 93.2%). Approximately half (50.4%) had Stage 3 disease and an additional 36.2% with stage 4, with the remainder Stage 1, 2 or Unknown. The majority (91.8%) were diagnosed with squamous cell carcinoma. 71.3% of patients received first line (1L) chemotherapy, most commonly with fluorouracil + cisplatin (69.9% of 1L) or platinum monotherapy (13.8% of 1L). 36.3% of patients survived one year with mean (SD) annualized post-index EC-related costs of New Taiwan (NT) $791,827.4 (NT$ 582,663.8). Conclusions: In Taiwan, the most common 1L chemotherapeutic treatment modality for Taiwanese patients with EC were fluorouracil + cisplatin. The EC-related costs for these patients appear to be a substantial financial burden in Taiwan.
Duloxetine (DL) in treatment of oxaliplatin-induced peripheral neuropathy (PN).
Authors: Chi Jeffrey , Fayyaz Fatima , Chung Su Yun , Jose Jyothi , Komorowski Anna W. , Dillon Maura , Shepherd Patnita , Gold Kenneth D. , Saif Wasif M. 
Published: January 2021

195 Background: Oxaliplatin is commonly used to treat many GI cancers, especially colorectal (CRC), pancreatic (PC), and gastric (GC); however, peripheral neuropathy (PN) is the dose-limiting toxicity. Duloxetine (DL) is a second-generation selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of depression, anxiety, PN-associated with diabetes or ongoing pain due to medical conditions such as fibromyalgia. In this retrospective study, we evaluated the role of DL in reduction of oxaliplatin-induced neuropathy. Methods: Patients with GI cancers receiving oxaliplatin-based chemotherapy regimens from Nov 2016 to Nov 2019 were included. Patients with pre-existing PN from other etiologies such as diabetes, alcoholism, autoimmune disease, infections, hereditary, etc. were excluded. Neurological evaluations were performed serially before initiating DL and every 4 weeks thereafter according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DL was given at 30 mg by mouth (PO) once daily and if tolerated after 3 days, was escalated to 60 mg once daily. Response was calculated to include number of patients with stable PN, improved PN, or no benefit. Adverse toxicities were graded. Results: 53 patients with median age of 53 years (range: 38 – 72) received DL for oxaliplatin-induced PN during treatment of GI cancers (CRC: 40%, PC:30%, GC: 10%, others: 10%). Improvement in PN from higher to lower grades was witnessed at 2 weeks in only 4 patients. At 4 week of DL, 3/53 (6%) patients improved from G3 PN to G2, 6/53 (11%) from G3 to G1, and 28/53 (52.8%) from G2 to G1, 14/53 (26%) and 2/53 (4%) had stable G3 and G2 PN respectively. At 8 week of DL, 10/53 (19%) of patients improved from G3 to G2, 3/53 (6%) from G2 to G1, 23/53 (43%) from G1 to G0, while 11/53 (21%), 2/53 (4%) and 4/53 (8%) remained stable at G1, G2 and G3 respectively. Overall DL resulted in a response rate of 89% and stable PN in 11%. 5 patients had to stop DL due to G3 drowsiness, insomnia, dry mouth and headache. Overall, DL was well-tolerated with majority of toxicities in G1-2 grade: dizziness (15%), drowsiness (11%), sexual side effects (11%), dry mouth (11%), insomnia (8%), headache (8%). In addition to PN, DL helped in improving depression in 50% of these patients and decreased the pain score in an additional 23%. Conclusions: DL resulted in a clinically significant improvement in PN-induced by oxaliplatin with manageable toxicity profile. Additionally, DL also improved depression and pain score. DL may be considered as an option in ameliorating PN in these patients, however, caution must be taken about DL and other drugs interaction. Our study warrants a prospective randomized trial to study the effectiveness of DL in treating oxaliplatin-induced PN. Moreover, cost effectiveness of DL in concurrently improving PN, depression and pain needs to be studied as well.
The impact of nutrition support in advanced gastric adenocarcinoma patients treated with chemotherapy.
Authors: Sugiyama Keiji , Shiraishi Kazuhiro , Motohashi Takuya , Onoda Shinpei , Noshibori Riko , Sato Mariko , Shimada Masaaki , Hirahsima Noboru , Kataoka Masato , Kitagawa Chiyoe 
Published: January 2021

208 Background: Numerous studies have demonstrated how malnutrition and cachexia are associated with poor survival in advanced gastric cancer (AGC). The impact of nutrition support involving multidisciplinary specialists is unclear, particularly among patients with AGC being treated with chemotherapy. This study aimed to clarify the differences in patient characteristics and survival outcomes between patients receiving nutrition support (NS) and routine care (RC). Methods: We retrospectively analyzed 212 consecutive patients with AGC at a single institution between January 2015 and June 2020. Inclusion criteria were: histologically confirmed metastatic or recurrent gastric and adenocarcinoma and gastroesophageal junction patients treated with chemotherapy, ECOG performance status (PS) 0-2, and adequate organ function. Time to treatment failure (TTF) in the entire cohort, patients with a positive Glasgow prognostic score (GPS) (graded as 1 and 2), and hypoalbuminemia (cutoff was 3.5 g/dl) were evaluated. Univariate and multivariate analyses were conducted to identify whether NS was an independent prognostic factor of time to treatment failure (TTF). Multivariate analysis included variables with p-values ≤0.1 in univariate analyses. Results: A total of 97 patients met the inclusion criteria with 67 (69%) and 30 (31%) patients classified into the RC or NS group, respectively. The median age was 71 years (range, 26-92). The median follow-up time was 8.4 months (range, 0.5-66). Patient characteristics revealed that NS was offered to patients with poorer prognostic nutritional index (PNI) (cutoff was 45, p=0.02), GPS positivity (p=0.01), and high neutrophil-lymphocyte ratio (NLR) (cutoff was 3, p=0.01). In the entire cohort, TTF in the RC and NS groups was 4.3 and 5.3 months (p=0.15), respectively. Among the patients with GPS positivity (graded as 1 and 2) and hypoalbuminemia, TTF in the RC and NS group were 2.3 and 5.0 months (p=0.05), and 2.3 and 5.3 months (p=0.02), respectively (Table). Variables with p-values ≤0.1 in univariate analyses for TTF were PS, NS, and prior gastrectomy. As per multivariate analyses, PS and NS were significant positive prognostic factors for TTF. Conclusions: NS was provided to patients with unfavorable clinical features. Among the AGC patients treated with chemotherapy, having GPS positivity or hypoalbuminemia seems to be a good indication for NS. [Table: see text]
Preoperative docetaxel, cisplatin, and 5-fluorouracil for resectable esophagogastric junction adenocarcinoma: A retrospective study.
Authors: Hirose Toshiharu , Yamamoto Shun , Oshima Kotoe , Hirano Hidekazu , Tsuda Natsuko Okita , Shoji Hirokazu , Iwasa Satoru , Honma Yoshitaka , Takashima Atsuo , Boku Narikazu , Oguma Zyunya , Ishiyama Koshiro , Daiko Hiroyuki , Kato Ken 
Published: January 2021

209 Background: In Western countries, 5-FU plus leucovorin, oxaliplatin, docetaxel (DTX) (FLOT) is the standard perioperative treatment for resectable gastric adenocarcinoma and esophagogastric junction adenocarcinoma (EGJ-AC). Preoperative chemotherapy with DTX plus cisplatin and 5-FU (DCF) has been developed for esophageal squamous cell carcinoma in Japan. However, there have been few reports on the safety and efficacy of preoperative triple therapy for resectable EGJ-AC. Methods: The subjects of this retrospective study were patients (pts) with histologically confirmed resectable EGJ-AC who received preoperative DCF chemotherapy (DTX 70 mg/㎡ and cisplatin 70 mg/㎡ on day 1, and continuous infusion of 5-FU 750 mg/㎡/day on days 1–5, every 3 weeks with a maximum of three cycles) at our hospital from Jan 2015 to Apr 2020. We evaluated the completion rate of >2 courses of DCF and R0 resection in all cases, and also examined histological response, progression-free survival (PFS), overall survival (OS), and adverse events during preoperative chemotherapy. Results: Thirty-two pts were included in this study, and the median observation period was 13.1 months (3.9–57.2). Characteristics were median age (range) 63 (42–80) years, PS 0/1 66/34%, clinical stage I/IIA/IIB/III/IVA/IVB (supraclavicular lymph node) 3/13/3/10/22/32/13%. Treatment completion rate was 84%. Histological response (grade 1a/1b/2/3) was obtained in 18/8/4/1 (58/26/13/3%) pts. Median PFS (95%CI) was 16.8 months (15.0–18.5), and median OS was not reached (3-year OS rate 73.8%). Grade >3 adverse events were observed in 20(63%) pts (neutropenia in 14 [44%], febrile neutropenia in 4 [13%]). No treatment-related deaths occurred. Conclusions: Preoperative DCF chemotherapy for resectable EGJ-AC was well tolerated. Further investigation is required to evaluate the long-term efficacy of this treatment strategy.
Comprehensive evaluation of genomic alterations in patients with gastric and gastroesophageal adenocarcinoma stratified according to TP53 mutation status.
Authors: Wood Anthony , Zhang Yonghong , Mo Qianxing , Cen Ling , Fontaine Jacques , Hoffe Sarah E. , Frakes Jessica M. , Dineen Sean P. , Pointer David T. , Pimiento Jose Mario , Mehta Rutika 
Published: January 2021

238 Background: Gastric (GC) and gastroesophageal adenocarcinomas (GEA) are molecularly diverse. Molecular biomarkers of clinical significance have been identified that impact treatment decision making. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. However, TP53 mutations have not yet been confirmed as a target of therapeutic benefit. This study aimed to identify distinct genomic alterations that are dominant in TP53 mutated (MUT) versus wild-type (WT) GC and GEA in order to elucidate alternative therapeutic targets within these subsets. Methods: De-identified data for 3741 patients with GC and GEA was obtained from Foundation Medicine. The data obtained were age, gender, tumor mutational burden (TMB), and the distinct genomic alterations noted on DNA sequencing. The dataset was sorted by TP53 mutation status. Differences in mutation frequency were detected using the Fisher’s exact test of independence with a p-value of < 0.01 designated as the cutoff value for statistical significance. Results: The dataset consisted of 2946 GCs and 795 GEAs. TP53 mutations were present in 65.8% of specimens. 61.6% of GCs and 81.4% of GEAs were TP53 MUT positive (p = < .001). Median TMB score and the frequency of tumors with a TMB score > 10 was similar in both TP53 MUT and WT groups. 49 genes had statistically different mutation frequencies in TP53 MUT vs. WT patients. Top co-occurring genetic alterations in TP53 MUT patients included amplification and point mutations in MYC, CCNE1, MET, ERBB2, and EGFR. Amplification and point mutations in MDM2, CDK4, ARID1A, PIK3CA, and ERBB3 were the top co-occurring genetic alterations in TP53 WT patients. Conclusions: There was a high frequency of TP53 mutations in this group of GC and GEA patients, with a higher incidence of TP53 mutations identified in GEA samples. The mutational profiles of these tumors differed according to TP53 mutation status. These differences may be able to serve as the foundation for future clinical investigations.