bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of cetuximab + FOLFIRI versus bevacizumab + FOLFIRI in the first-line treatment of RAS wild-type metastatic colorectal cancer in China.
Authors: Van Oostrum Ilse , Hu Yannan , Yuan Zijiao , Schlichting Michael , Tao Libo , Pescott Chris P. 
Published: January 2021

133 Background: Adding cetuximab to FOLFIRI chemotherapy (cet+CT) as first-line (1L) treatment for RAS wild-type (wt) metastatic colorectal cancer (mCRC) has been reported as cost-effective vs bevacizumab + FOLFIRI (bev+CT) in multiple jurisdictions. This study determined the cost-effectiveness (CE) of cet+CT for patients with mCRC in China. Methods: A published 3–health-state (nonprogressive, progressive, death) CE model was adapted to reflect Chinese patient characteristics, health state utilities, unit costs, and discounting rates, applying FIRE-3 trial–based resource utilization and adverse event rates. Progression-free and overall survival estimates were based on published FIRE-3 trial simulations to statistically adjust for available later-line treatment modalities in China vs those observed in FIRE-3. [1] Cetuximab and bevacizumab costs were based on up-to-date prices after the 2019 national reimbursement drug listing negotiations. Incremental CE ratios (ICERs) are given as cost (Chinese Yuan [¥]) per life-year (LY) and quality-adjusted LY (QALY) gained. The willingness-to-pay (WTP) threshold was ¥193,931, equivalent to 3 times the gross domestic product per capita, following WHO guidance. Results: Overall costs/costs restricted to 1L treatment were ¥483,771/¥249,619 (cet+CT) and ¥366,036/¥156,802 (bev+CT). Health effects were 3.32/2.68 (cet+CT) and 2.39/1.94 (bev+CT) LYs/QALYs gained. Discounted ICERs for cet+CT vs bev+CT were ¥148,311 and ¥186,517 per LY and QALY gained in deterministic analysis. cet+CT had a 71.8% (LY) and 52.5% (QALY) probability of being cost-effective. Treatment duration with a biologic in 1L, utilities in 3L treatment, and duration of 2L treatment were the main outcome drivers. Conclusions: Projections suggest that cet+CT is cost-effective vs bev+CT for 1L treatment of patients with RAS wt mCRC in China, with ICERs below the current WTP threshold in deterministic and probabilistic sensitivity analyses. [1] Van Oostrum I, et al. Value Health. 2020;23(Suppl 1): S8.
Impact of preoperative therapy for locally advanced thoracic esophageal cancer on the risk of perioperative complications: Results from multicenter phase III trial JCOG 1109.
Authors: Koyanagi Kazuo , Kato Ken , Ito Yoshinori , Daiko Hiroyuki , Ozawa Soji , Ogata Takashi , Hara Hiroki , Kojima Takashi , Abe Tetsuya , Bamba Takeo , Watanabe Masaya , Kawakubo Hirofumi , Shibuya Yuichi , Tsubosa Yasuhiro , Tsuda Masahiro , Nozaki Isao , Baba Hideo , Machida Ryunosuke , Fukuda Haruhiko , Kitagawa Yuko ,   The Japan Esophageal Oncology Group/Japan Clinical Oncology Group
Published: January 2021

162 Background: We have conducted randomized three-arm phase III trial comparing cisplatin plus 5-FU (CF) versus docetaxel plus CF (DCF) versus radiation with CF (CF-RT) as preoperative therapy for locally advanced esophageal cancer, which is on-follow-up for primary analysis planned in 2023 (JCOG 1109). This study aimed to evaluate the influence of preoperative therapies on perioperative complications and risk factors for perioperative complications after three-arm preoperative therapies. Methods: Patients with potentially resectable advanced thoracic esophageal cancer were randomly assigned to three preoperative therapies and followed by open or thoracoscopic esophagectomy with regional lymphadenectomy. Clinical data, surgical results, and perioperative complications in the patients received DCF and CF-RT were compared with those in the patients received CF. Univariate and multivariate analyses were performed to explore the risk factors of perioperative complications. Results: Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200). Of 589 eligible patients, 546 patients underwent surgery (185/183/178). Patients` characteristics were not different between arms. Median number of harvested lymph node in patients received CF-RT was significantly lower than that in patients received CF (49 vs. 58; P < 0.0001). Incidence of ≥ Grade 2 perioperative complications in patients received DCF was lower than that in patients received CF (44.8% vs. 56.2%; P = 0.036). Incidence of ≥ Grade 2 chylothorax in patients received CF-RT was higher than that in patients received CF (5.1% vs. 1.1%; P = 0.032). Incidence of reoperation and intra-hospital death in patients received DCF and CF-RT did not differ from that in patients received CF. Multivariate analysis showed that operation time (≥ median) and open esophagectomy were independently associated with an increase in ≥ Grade 2 perioperative complications. CF-RT was associated with an increase in occurrence of ≥ Grade 2 chylothorax (Relative Risk 4.84; P = 0.043). Conclusions: Preoperative DCF and CF-RT does not increase the risk of perioperative complications and mortality when compared with standard preoperative CF therapy, but CF-RT increases the risk of chylothorax after esophagectomy for advanced thoracic esophageal cancer.
Outcomes of a phase II study of intraperitoneal paclitaxel plus systemic capecitabine and oxaliplatin (XELOX) for gastric cancer with peritoneal metastases.
Authors: Chia Daryl , Sundar Raghav , Kim Guo Wei , Ang Jiajun , Lum Jeffrey , Nga Min En , Cheng Ean Chee , Tan Hon Lyn , Ho Jingshan , Ngoi Natalie , Lee Matilda , Muthu Vaishnavi , Chan Gloria , Pang Angela , Ang Yvonne , Choo Joan , Lim Joline Si Jing , Shabbir Asim , Yong Wei-Peng , So Jimmy Bok Yan 
Published: January 2021

165 Background: The addition of intraperitoneal (IP) paclitaxel (PTX) to systemic chemotherapy comprising taxane/fluoropyrimidine doublet has shown promising results for patients with gastric cancer (GC) and peritoneal metastases (PM). However, this has not been studied in combination with platinum/fluoropyrimidine doublet which is the current standard-of-care for metastatic GC. We conducted a prospective phase 2 trial of IP PTX with capecitabine and oxaliplatin (XELOX) in patients with GCPM. Methods: The trial enrolled 44 patients with GCPM who received treatment comprising IP PTX (40mg/m2 on day 1,8), PO capecitabine (1000mg/m2 twice daily from day 1-14) and IV oxaliplatin (100mg/m2 on day 1) in 21-day cycles. Patients with synchronous GCPM were eligible for conversion surgery comprising radical gastrectomy if they had good response after chemotherapy, negative cytology on 2 consecutive peritoneal fluid assessments, no extraperitoneal metastasis and no peritoneal disease during surgery. The primary endpoint was overall survival and secondary endpoints were progression-free survival and safety. Outcomes from the trial were also compared with a retrospective cohort of 39 patients with GCPM who received identical systemic chemotherapy (SC) comprising platinum/fluoropyrimidine agents alone. Results: The median OS for the IP and SC groups was 14.6 and 10.6 months (HR 0.44; 95% CI, 0.26-0.74; P=0.002). The 1-year OS was 67.8% in the IP group and 32.3% in the SC group (Logrank p<0.001). The median PFS for the IP and SC group was 9.5 and 4.4 months respectively (HR 0.39; 95% CI, 0.25-0.66; P<0.001). Patients in the SC group were younger (IP vs. SC, 61 vs. 56 years, p=0.021) and had better baseline performance status (ECOG 0, IP vs. SC, 47.7% vs. 76.9%, p=0.007) compared to the IP cohort. In the IP group, conversion surgery was performed in 36.1% (13/36) of patients, with a median OS of 24.2 (95%CI 13.1 – 35.3) months and 1-year OS of 84.6%. Wound-related complications requiring the port to be explanted or re-sited occurred in 9% (4/44) of patients. Conclusions: IP PTX with XELOX is a promising treatment option for GCPM patients. For patients with good response, conversion surgery was feasible with favourable outcomes. Clinical trial information: NCT01739894. [Table: see text]
Esophagectomies for malignancy among general and thoracic surgeons: A propensity score-matched NSQIP analysis stratified by surgical approach.
Authors: Leonard-Murali Shravan , Ivanics Tommy , Nasser Hassan , Tang Amy , Hammoud Zane T. 
Published: January 2021

166 Background: Training of general and thoracic surgeons continues to diverge, especially with the increasing role for minimally invasive surgical (MIS) approaches. Previous studies of esophagectomy outcomes by specialty do not adequately address malignancy or surgical approach. We sought to evaluate perioperative outcomes of esophagectomy for malignancy stratified by surgical specialty and approach using a national database. Methods: The National Surgical Quality Improvement Program (NSQIP) Targeted Esophagectomy Dataset was queried for esophagectomies for malignancy and grouped by surgeon specialty: thoracic surgery (TS) or general surgery (GS). Those with missing data were excluded (n = 6). To account for confounding due to specialty selection bias, we performed propensity score matching (PSM) by age, body mass index, ethnicity, American Society of Anesthesiologists class ³ 3, and surgical approach in a 1:1 ratio. An absolute standardized difference of ≤ 0.1 was considered an appropriate balance. The primary outcome was mortality and secondary outcomes were anastomotic leak, Clavien-Dindo grade ≥ 3 and positive margin rate. Univariate logistic regression analysis was performed for these outcomes on the matched cohort, with stratification by surgical approach (open vs. MIS). Results: A total of 1463 patients met inclusion criteria (512 GS, 951 TS). After PSM each group was comprised of 512 patients with similar demographics, neoadjuvant chemotherapy and radiation rates, and preoperative stage. The TS group consisted of 169 (33.0%) open and 343 (67.0%) MIS cases, while the GS group consisted of 177 (34.6%) open and 335 (65.4%) MIS cases. Postoperative complications, including surgical site infection, pneumonia, pulmonary embolism, stroke, and myocardial infarction were similar between matched groups, and remained similar when stratified by surgical approach. Mortality rates were similar between the TS and GS groups, both overall (14 (2.7%) vs. 10 (2.0%)) and when stratified by surgical approach (MIS: 11 (3.2%) vs. 10 (3.0%), open: 3 (1.8%) vs. 0 (0%)). By univariate analysis of the matched cohort stratified by surgical approach, TS patients had similar odds as GS patients of anastomotic leak (open: adjusted odds ratio (AOR) = 1.11, 95% confidence interval (95%CI) = 0.58 – 2.15, p = 0.75; MIS: AOR = 0.70, 95%CI = 0.47 – 1.04, p = 0.08), Clavien-Dindo grade ≥ 3 (open: AOR = 1.27, 95%CI = 0.79 – 2.06, p = 0.32; MIS: AOR = 1.01, 95%CI = 0.73 – 1.39, p = 0.97), positive surgical margins (open: AOR = 0.75, 95%CI = 0.33 – 1.68, p = 0.49; MIS: AOR = 0.62, 95%CI = 0.35 – 1.07, p = 0.09), and mortality (open: unable to be calculated due to 0 deaths in the GS group; MIS: AOR = 1.08, 95%CI = 0.45 – 2.62, p = 0.87). Conclusions: Esophagectomy for malignancy had a similar perioperative safety profile and positive margin rate among general and thoracic surgeons, regardless of surgical approach.
The effect of gender on outcomes in esophageal cancer.
Authors: McDonald Jordan , Saeed Sabrina , Hoffe Sarah E. , Mehta Rutika , Frakes Jessica M. , Fontaine Jacques-Pierre , Dineen Sean P. , Pimiento Jose Mario 
Published: January 2021

170 Background: Few epidemiological studies address differences in outcomes by gender in locoregional esophageal cancer (LEC) for which the current standard of care is chemoradiation followed by surgical resection. Although male gender is associated with the majority of LEC cases, we sought to determine if gender could impact clinical presentation as well as surgical and oncologic outcomes in our single institution 20 year experience. Methods: A retrospective query of our institution’s IRB-approved database of patients that had surgical therapy between 2008 and 2019 for esophageal cancer (EC) was performed. Patients were stratified by gender and analyzed based on characteristics such as tumor histology, tumor location, clinical stage at presentation, age at diagnosis, receipt of neoadjuvant therapy, surgical intent, surgical complications, length of post-operative hospital stay, response to neoadjuvant therapy, final pathology, and recurrence. Chi-square, ANOVA and Kaplan Meier survival analysis were performed on the previously defined groups. Results: The cohort studied included 1180 patients with resection for EC. Of those, 1005 (85.2%) had adenocarcinoma, 145 (12.3%) had squamous cell cancer (SCC), 10 (0.8%) had adenosquamous carcinoma, and 20 (1.7%) had other histological variants. There were 985 (83.5%) male patients and 195 (16.5%) female patients. SCC was more common in females (29.2% in females vs. 8.9% in males, p = 0.000) and females tended to have tumor location in the upper thoracic esophagus more often (4.7% in females vs. 0.9% of males, p = 0.000). Additionally, females developed surgical complications more often than males (72.2% vs. 64.7%, p = 0.045). Staging at diagnosis (p = 0.508), receipt of neoadjuvant treatment (p = 0.676), and age at diagnosis (65.3 years in males vs. 66.3 years in females, p = 0.934) had no association with gender. Response to neoadjuvant therapy (p = 0.157) and cancer recurrence (p = 0.434) did not have significant associations with gender. The median overall survival was not statistically significantly different but trended to be longer for females (73.4 months in females [95% CI: 51.5-95.4] vs. 47.0 months in males [95% CI: 39.6-54.5], p = 0.160). Conclusions: Based on our high-volume cancer center study, female patients were more likely to have SCC, upper thoracic esophageal lesions, and surgical complications following resection. While univariate analysis did not demonstrate significant differences in overall survival between genders, there are plans to report additional data after controlling for other variables. Further studies are warranted to validate these findings, given the potential for higher prioritization of an organ preservation approach for this patient population.
Factors associated with treatment duration from start of second-line ramucirumab plus paclitaxel or nab-PTX for advanced gastric cancer: real-world evidence from Japanese Claim Database.
Authors: Hironaka Shuichi , Komatsu Yoshito , Tanizawa Yoshinori , Cai Zhihong , Piao Yongzhe , Boku Narikazu 
Published: January 2021

177 Background: Recently, the value of RWE has been recognized to be important. We investigated the first line(1L)-2L therapy(Tx) sequence for AGC and factors associated with whole treatment period after RAM plus(+) (nab-)PTX therapy using RWE in Japan. Methods: This study used a hospital-based claims database in Japan. Patients who were diagnosed with GC and started 1L Tx between Jun 2015 and Jul 2019 were selected. The 1L Tx was defined as fluoropyrimidine(FP)+platinum (with or without trastuzumab[Tmab]), and defined to be discontinued when it was suspended for >90 days or switched to different antitumor drugs (2L Tx). In patients who started RAM+(nab-)PTX as 2L Tx, factors associated with overall Tx duration (from start of 2L Tx to the last dose of chemotherapy including subsequent Tx) were explored by Cox regression analysis. Results: 10581 patients (mean age 67.9 years, male 73.9%) received 1L Tx (9024 patients without Tmab and 1557 patients with Tmab). In patients who discontinued 1L Tx, the proportion of 1L-2L Tx transition was 61% (4509/7443) without Tmab and 68% (849/1245) with Tmab. Among 5358 patients who received 2L Tx, 3650 patients (68%) received RAM+(nab-)PTX. The median overall Tx duration was 6.7 months after initiation of 2L Tx with RAM+(nab-)PTX. Factors positively associated with the overall Tx duration from initiation of 2L Tx with RAM+(nab-)PTX were Tmab use before data cutoff (Sep 2019; hazard ratio [95% CI] 0.9 [0.79-1.00]), previous oral FP (0.7 [0.54-0.89]), duration of 1L Tx >150 days (0.8 [0.74-0.87]). Factors negatively associated were peritoneal metastasis or ascites (1.3 [1.17-1.40]), comorbidities e.g., edema (1.3 [1.07-1.45]), renal disease (1.1 [1.01-1.30]), diabetes (1.1 [1.01-1.22]), previous oxaliplatin (1.2 [1.09-1.30]), and rehabilitation (1.9 [1.67-2.24]) or nutritional intervention (1.5 [1.34-1.68]) within 1 month before and after starting 2L Tx. Conclusions: Many of the patients received RAM+(nab-)PTX as 2L Tx regardless of Tmab. This large-scale RWE demonstrated that Tmab use, oral FP, and long 1L Tx duration were associated with longer treatment course from start of 2L RAM+(nab-)PTX therapy.
Efficacy and safety of apatinib in treatment of gastric cancer: A real-world study.
Authors: Ma Yijie , Zong Hong , Wang Junsheng , Guo Yanzhen , LIU Huaimin , Li Ning , Cang Shundong , Shang Ke , Chen Xiaobing , Wang Jin , He Dezhi , Deng Wenying , Sun Peichun , Zhang Zhen , Zhang Liguo , Xu Feng , Tian Chuntao , Qiao Chaofeng , Chen Gongbin , Luo Suxia 
Published: January 2021

182 Background: Apatinib is a small molecule TKI inhibitor, which had been approved in China for treatment of advanced gastric cancer refractory to two or more lines of prior chemotherapy. Its efficacy and safety have been demonstrated in previous randomized controlled clinical studies. However, the efficacy and safety of apatinib in real world is lacking. This study aimed to evaluate the anti-tumor activity and toxicity of apatinib in real world. Methods: Patients older than 18 years with histologically diagnosed with gastric cancer were enrolled and treated with either apatinib alone or in combination with other drugs. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR) and disease control rate (DCR). The adverse events were also recorded. Results: From March 2018 to March 2019, a total of 1000 patients were enrolled. Among them, 48(0.48%), 13(0.13%), 225 (22.5%), 389 (38.9%), and 325 (32.5%) patients received apatinib as postoperative auxiliary-, neoadjuvant-, first-, second-, and third- or higher line therapy, respectively. Efficacy evaluation was performed in 901 patients. Thirty-five patients achieved complete response (CR), 116 patients achieved partial response (PR), 596 patients achieved stable disease (SD), and 154 patients had progressive disease (PD), illustrating an ORR of 16.76% and a DCR of 82.91%. The mPFS was 5.32 months (95% CI, 4.93-5.75), and mOS was 9.76 months (95% CI, 8.97-10.81). In addition, the mOS of apatinib in first-line, second-line, and third-line treatments were 12.68 months, 9.49 months, and 7.62 months, respectively. Patients received apatinib in combination with other drugs had longer survival than apatinib alone, with mPFS 5.62 months vs 4.47 months and mOS 10.81 months vs 7.95 months. Such phenomenon was also observed in ORR (18.21% vs 13.04%, P< 0.001) and DCR (84.88% vs 77.87%, P< 0.001). The main adverse events (AE) were anemia (67.2%), thrombocytopenia (36.2%), leukopenia (34.5%)and anorexia (37.6%). The most common grade 3-4 adverse events included neutropenia, anemia and thrombocytopenia. Conclusions: In the real world, apatinib showed promising efficacy and manageable toxicities in patients with gastric cancer. Patients benefit more when received apatinib combination therapy. Clinical trial information: NCT03478943.
A multicountry chart review of treatment patterns and outcomes for patients with resected esophageal or gastroesophageal junction cancer.
Authors: Singh Prianka , Gricar Joseph , Mackie deMauri S , Xiao Hong , DeCongelio Marc , Jaffe Dena H. 
Published: January 2021

184 Background: Global neoadjuvant and adjuvant treatment patterns among patients with resected Esophageal Cancer (EC) and Gastroesophageal Junction cancer (GEJC) remain unclear. This study describes real-world treatment patterns and outcomes for patients receiving surgery for Stage II or III EC or GEJC. Methods: Physicians in North America (US, Canada), Asia (China, Japan, Taiwan), and Europe (UK, France, Germany, Italy, Spain) provided clinical and treatment data in this retrospective, non-interventional chart review conducted from April-June 2020. Included patients were adults (Japan ≥20 years; elsewhere, ≥18 years), who underwent resection of Stage II or III EC or GEJC between October 2017 and October 2018 and were followed until death, loss to follow up, or end of data collection. Results: Physicians (N = 609) provided data on 1693 patients of mean age of 62.4 years, who received surgery for Stage II or III esophageal squamous cell carcinoma (ESCC) (33.3%), esophageal adenocarcinoma (EAC) (31.5%), or GEJC (35.2%) and were followed a mean (median) of 17.7 (17) months (to death or end of study period). At diagnosis, 85.6% of patients had performance status of 0/1. The majority of patients received an R0 resection (overall, 70.6%; ESCC, 76.6%, EAC, 67.4%, GEJC, 68.0%; p < 0.05); of these, 32.0% had a complete pathological response and 64.1% had a partial pathological response. Neoadjuvant therapy use differed among the treatment groups (ESCC 56.5%; EAC, 65.9%; GEJC, 62.6%, p < 0.05), as did adjuvant therapy (ESCC: 39.8%; EAC, 40.3%; GEJC, 44.5%; p = 0.023). Recurrence rate following surgery did not differ between groups for any recurrence (overall, 21.0%; ESCC 18.5%, EAC 23.6%, GEJC 21.1%); for local or regional recurrence (overall, 11.6%; ESCC, 10.3%; EAC, 12.7%; GEJC, 11.7%); or for metastatic recurrence (overall, 9.5%; ESCC, 8.2%; EAC, 10.9%; GEJC, 9.4%). The median time to local or regional recurrence (for those who progressed during the reporting period) was 8 months from date of initial surgery (overall, 8 mo; ESCC, 8 mo; EAC, 7 mo; GEJC, 8.5 mo; p > 0.05). The frequency of 1L systemic therapy for advanced disease at the time of survey completion was 16.1% overall and differed among patients with ESCC (14.6%); EAC (17.8%); and GEJC (15.9%); p > 0.05. Conclusions: This large multi-country real world data study shows that over half of all patients received neoadjuvant therapy, and over a third received adjuvant treatment. The high unmet need in this population is evident from the post-resection recurrence rate of 21.1% at median 8 months and the high proportion of patients who went on to require advanced disease treatment.