bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic landscape of ERBB2/3 alterations in colorectal cancer: Comutations, immuno-oncology biomarkers, and consensus molecular subtype.
Authors: Tie Jeanne , El-Refai Sherif Mohamed , Yoshino Takayuki , Siena Salvatore , Lonardi Sara , Sartore-Bianchi Andrea , Nakamura Yoshiaki , Bando Hideaki , Fujisawa Takao , Lok Sheau Wen , Wong Hui-Li , Kadakia Kunal C. , Mauer Elizabeth , Salem Mohamed E. 
Published: January 2022

176 Background: ERBB2 is a rapidly emerging therapeutic target for a subset of colorectal cancer (CRC) harboring oncogenic alterations in this gene. Oncogenic ERBB3 mutations have been reported in various cancers including CRC, but little is known about its functional impact. Optimal targeting of this pathway requires understanding of the genomic context in which somatic ERBB2/3 alterations ( ERBB2/3-alt) occur in a real-world CRC population. Methods: We analyzed 7,688 de-identified records from CRC patients that underwent next generation sequencing with the Tempus|xT assay (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq). We assessed the prevalence and association of ERBB2/3-alt with demographics, co-occurring alterations, immuno-oncology biomarkers (microsatellite instability [MSI], tumor mutational burden [TMB], PD-L1 expression), and consensus molecular subtype (CMS, available for the subgroup with primary biopsies and RNA data [n = 2,686]). Results: Overall, 5% (376/7688) of tumors harbored an ERBB2 or ERBB3-alt. 1.9% (n = 143) ERBB2-amplified, 1.3% (n = 97) ERBB2-mutated, 0.9% (n = 72) ERBB3-mutated, < 1% other combinations (excluded from analyses). There were no significant differences in baseline demographics (e.g., age of onset, race and gender) between groups. Patients with ERBB2/3-alt were more likely to be MSI-high and TMB-high (Table). There was a trend towards higher prevalence of positive PD-L1 in ERBB3-alt vs ERBB3-WT tumors. We observed significant differences in co-occurring alterations among ERBB2/3-alt and WT groups (Table). CMS classification did not identify significant differences by ERBB2-alt or ERBB3-alt; ERBB2-alt compared to WT (CMS1: 8.6% vs 13%; CMS2: 24% vs 26%; CMS3: 20% vs 17%; CMS4: 30% vs 34%; p = 0.12) and ERBB3-alt compared to WT (CMS1: 24% vs 13%; CMS2: 12% vs 26%; CMS3: 16% vs 17%; CMS4: 40% vs 34%; p = 0.3). Conclusions: ERBB2/3 mutated CRC are more frequently MSI-H, TMB-high and KRAS mutated than ERBB2/3-WT tumors. Correlation of ERBB2/3 alterations with other genomic alterations including BRAF, TP53, CDK12, PIK3CA, and TOP2A will help advance the clinical development of HER2-targeted therapies.[Table: see text]
Clinical implication of KRAS mutation variants in patients with resected colon cancer.
Authors: Baek Jin Ho , Kang Byung Woog , Choi Gyu Seog , Kim Jong Gwang 
Published: January 2022

179 Background: This study evaluated the clinical implication of KRAS mutation variants in patients with resected colon cancer (CC). Methods: We retrospectively reviewed 482 patients diagnosed with CC and underwent curative surgical resection at Kyungpook National University Chilgok Hospital. The inclusion criteria were: pathologically diagnosed with primary CC; stage I–III CC according to the 7th edition of American Joint Committee on Cancer staging system; and with available test results for KRAS mutation status. In total, 345 patients met these criteria and were included in this study. Results: Among the 345 patients, 140 (40.6%) exhibited KRAS mutations, with their incidences as follows: 90/140 (64.3%) in Exon 2 Codon 12, 37/140 (26.4%) in Exon 2 Codon 13, 1/140 (0.1%) in Exon 3 Codon 59, 7/140 (5.0%) in Exon 3 Codon 61, and 5/140 (3.6%) in Exon 4 Codon 146. KRAS mutation status was not a significant prognostic factor for disease-free survival (DFS) or overall survival (OS). Although, there were no significant differences in survival between patients with Exon 2 Codon 12 and Exon 2 Codon 13 mutations, poorer DFS ( p = 0.085) and OS ( p = 0.005) were seen in those with Exon 3 Codon 61 mutation than in others. Conclusions: KRAS mutation status was not correlated with survival, but Exon 3 Codon 61 mutation might be a poor prognostic factor in resected CC patients.
Efficacy of regorafenib and 5-fluorouracil-based rechallenge treatment in the third-line treatment of metastatic colorectal cancer: A Turkish oncology group study.
Authors: Şenocak Taşçi Elif , Oyan Basak , Sonmez Ozlem , Mutlu Arda Ulaş , Atcı Muhammed Mustafa , Oner Irem , Yesil Cinkir Havva , Karakurt Eryılmaz Melek , Yazdan Balçık Onur , Paksoy Nail , Kivrak Salim Derya , Özen Mirac , Ozcelik Melike , Arican Ali , Inal Ali , Akagunduz Baran , Aydın Dinçer , Ozer Leyla , Turhal Nazim Serdar , Gulmez Ahmet 
Published: January 2022

202 Background: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib (Reg) revealed promising results by improving overall survival compared to best supportive care. However, in real-world practice rechallenge chemotherapy (CTr) is often preferred even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. Methods: In this retrospective multi-institutional trial, mCRC patients from 21 centers in Turkey progressing after 2 lines of chemotherapy between 2012-2020 were analyzed. Patients who were treated with Reg or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. Overall survival (OS), objective response rate (ORR), progression free survival (PFS) and toxicity were analyzed. Chi-square, Kaplan-Meier method and Cox regression analysis were used for analysis. Results: The clinical data of 441 mCRC patients were analyzed. Of these, 284 received regorafenib while 156 received rechallenge chemotherapy. The mean age was 57 and 56% was male. Median OS since the diagnosis was better with CTr than with Reg (48 months (95% CI, 43.4–52.6) vs. 39 months (95% CI, 35.4–42.5), p<0.001). Median OS after the third-line treatment was 12.0 (95% CI, 9.9–14) and 9.0 months (95% CI, 7.5–10.4) for CTr and Reg groups, respectively (p<0.001). PFS was 6 months for patients receiving CTr and 4 months for those treated with Reg (p = 0.139). ORR was significantly higher in CTr group than Reg (p<0.001). BRAF status, MSI status and treatment type (CTr vs. Reg) are factors found associated with OS in Cox regression analysis (p<0.001, p=0.021 and p<0.001, respectively). Adverse effects were seen in 82% and 68.2% of patients receiving Reg and CTr, respectively. Discontinuation of treatment due to adverse effects was higher in patients treated with Reg (10% vs. 2.5%). Conclusions: Our analysis revealed that rechallenge is an appreciated option, in both efficacy and toxicity, when the limited treatment options for mCRC is considered. Although regorafenib treatment contributes to survival, CTr shows better disease control. Our study has the highest number of patients in the literature. Still, prospective studies are mandatory for validation of CTr in the third-line treatment of mCRC.
Neoadjuvant nivolumab plus ipilimumab and adjuvant nivolumab in patients (pts) with localized microsatellite instability-high (MSI)/mismatch repair deficient (dMMR) oeso-gastric adenocarcinoma (OGA): The GERCOR NEONIPIGA phase II study.
Authors: Andre Thierry , Tougeron David , Piessen Guillaume , De La Fouchardiere Christelle , Louvet Christophe , Adenis Antoine , Jary Marine , Tournigand Christophe , Aparicio Thomas , Desrame Jérôme , Lièvre Astrid , Garcia-Larnicol Marie-Line , Pudlarz Thomas , Henriques Julie , Cohen Romain , Lefevre Jérémie , Svrcek Magali 
Published: January 2022

244 Background: In pts with resectable gastric adenocarcinoma or OGA, radical surgery is the only curative option and perioperative chemotherapy seems worthless for those with MSI/dMMR tumors. Methods: We conducted phase II study evaluating the efficacy of neo-adjuvant nivolumab and ipilimumab followed by adjuvant nivolumab in pts with resectable MSI/dMMR, T2-T4 NxM0 tumors. Treatment consisted of nivolumab 240 mg every 2 weeks (6 infusions) and ipilimumab 1 mg/kg every 6 weeks (2 infusions), followed by radical surgery 5 weeks (±1 week) after last injection of nivolumab. Pts with Becker tumor regression grade (TRG) < 3 were treated with adjuvant nivolumab 480 mg every 4 weeks (9 infusions). The primary objective was pathological complete response (pCR) rate. Results: From 10/2019 to 06/2021, a total of 32 pts were enrolled (all had dMMR±MSI-H status; 16 with gastric cancer and 16 with OGA). The median age was 65.5 years (range, 40-80). Initial stage was: usT3Nx = 22, usT2Nx = 4, and usTxNx = 6 (not evaluable by ultrasound endoscopy). At data lock, 32 pts had terminated neo-adjuvant period and 27 (84%) completed all 6 neo-adjuvant cycles. 8 pts (32%) experienced G3/4 adverse events (AEs) during neo-adjuvant treatment. 29 pts underwent surgery; 2 refused surgery and had complete endoscopic response with tumor-free biopsies, 1 had surgery not performed in relation with a metastatic progression. The median delay between last injection and surgery was 35 days (extreme, 25-170). Overall surgical morbidity (54%, n = 14) was related to: anastomotic leakage = 4, pancreatitis = 2, pneumonia = 2, and other = 6. The incidence of post-operative mortality was 3.8% (n = 1) due to cardiovascular AE at post-operative day 3. All the 29 pts who underwent surgery had R0 resection: 17 (59%) had pCR (i.e., TRG 1a as per Becker grade, ypT0N0) and 4 (14%) had TRG 1b as per Beker grade (< 10% residual tumor per tumor bed). 1 pt had TRG 2 (10-50% of residual tumor) and 7 pts had TRG 3 (˃50% of residual tumor) as per Becker grade, per local pathological assessment (central pathological review is awaited). With a median follow-up of 10.9 months, 1 pt had metastatic relapse, 1 pt died without relapse and 30 pts were recurrence/progression-free. Conclusions: Neo-adjuvant therapy with nivolumab and ipilimumab is feasible and is associated with a high pCR rate in pts with MSI/dMMR resectable OGA. Data will be updated for the congress. Clinical trial information: NCT04006262.
Changing epidemiology of esophageal cancer: A population-based study over 43 years (1975–2018).
Authors: Bien Jeffrey , Nguyen Theresa Hoang-Anh , Aljehani Mayada , Lee Jerry S.H. , Wang David H. , Lin Albert Y. 
Published: January 2022

247 Background: Esophageal cancer (EC) is the seventh most common cancer worldwide. Previous studies have indicated that the incidence of squamous cell carcinoma of the esophagus (SCE) in the US has declined since the 1970s. In comparison, the incidence of adenocarcinoma of the esophagus (ACE) has sharply risen in the US since the 1970s. This study aimed to examine temporal trends in incidence rates of EC, ACE, and SCE that include recent decades. Methods: Data were derived from the Surveillance, Epidemiology, and End Results (SEER) of the National Cancer Institute - a population-based cancer database. Using SEER*Stat, we calculated the age-adjusted incidence rates (AAIR) for EC, ACE, and SCE in both SEER 9 (for longest follow-up time) and SEER 21 (the largest cohort covering 36.7% of the US population). Temporal incidence trends were examined using Joinpoint analyses to estimate the annual percent change (APC). Subgroup analyses were performed for sex, age, and race/ethnicity. Results: See Table. When stratified by age, age <64 years had a significant decrease in incidence with an APC of -1.1 (2007-2018), while the incidence plateaued in the remaining age groups. The rise in incidence was highest among non-Hispanic whites (NHW) from 2000-2004 (APC 4.0), especially NHW males (APC 3.0); however, the incidence plateaued in all race/ethnicity groups after 2006. Conclusions: The AAIR of EC as a whole has been decreasing since 2004. The AAIR of ACE has, for the first time, plateaued in the most recent decade (2006-2018), after having risen for three preceding decades (1975-2006); we find this effect is mainly driven by the AAIR from NHW males, age <64 years. The incidence of SCE has continued to decline since 1975. Future studies should further explore the underlying etiology of these patterns.[Table: see text]
Efficacy and safety of neoadjuvant chemotherapy for locally advanced gastric cancer in elderly patients: A phase II trial (KSCC1801).
Authors: Uehara Hideo , Ota Mitsuhiko , Matsuda Yoshiko , Tsutsumi Satoshi , Kusumoto Tetsuya , Yasui Hisateru , Ubukata Yasunari , Yamaguchi Shohei , Orita Hiroyuki , Horie Yoshiki , Kakizoe Saburo , Shimokawa Mototsugu , Oki Eiji , Kakeji Yoshihiro , Saeki Hiroshi , Mori Masaki 
Published: January 2022

254 Background: Gastrectomy with D2 dissection and adjuvant chemotherapy is currently the standard treatment for locally advanced gastric cancer (LAGC) in Asian countries. However, administering chemotherapy with sufficient intensity after gastrectomy is often challenging. Thus, several trials have been undertaken to demonstrate the efficacy of neoadjuvant chemotherapy (NAC). NAC-SOX regimen for LAGC has been already shown to reduce distant micro-metastasis and to improve the R0 resection rate by tumor shrinkage in Asian trials. However, there have been few studies of the feasibility of NAC-SOX for elderly patients with LAGC. KSCC1801 is a phase II study to evaluate the safety and efficacy of NAC-SOX in elderly patients aged 70 years or over with LAGC. Methods: Patients received three cycles of SOX as neoadjuvant chemotherapy followed by gastrectomy with D2 dissection. Oxaliplatin was administered intravenously (130 mg/m2) on day 1, and S-1 was administered orally (80- 120 mg/day) for 14 days followed by 7-day rest period. The primary endpoint was the dose intensity (DI). A sample size of 25 was set according to a one-sided significance level of 0.025 and a power of 80% on the basis of a one-sample t-test and assuming a null hypothesis of a 75% DI and an alternative hypothesis of an 85% DI with an estimated standard deviation of 14%. The secondary endpoints were safety, R0 resection rate, response rate, overall survival, and relapse-free survival. Results: Twenty-six patients were enrolled in this study. The median age was 74.5 years. The median DI in NAC-SOX was 97.2% for S-1 and 98.3% for oxaliplatin. Three cycles of NAC could be performed in 25 patients (96.2%), of whom 23 (88.5%) underwent gastrectomy with D2 dissection. The R0 resection rate was 92.3% and the pathological response rate (≥grade 1b) was 62.5% [95% confidence interval: 40.6 - 81.2]. The major adverse events (≥grade 3) were neutropenia (20.0%), thrombocytopenia (11.5%), anorexia (11.5%), nausea (7.7%) and hyponatremia (7.7%). Postoperative complications of abdominal infection, elevated blood amylase, and bacteremia occurred in one patient each. One treatment-related death occurred, probably due to severe diarrhea and dehydration. Conclusions: NAC-SOX was feasible and promising even in elderly patients. Systemic management and more careful monitoring of adverse events are necessary for elderly patients. Clinical trial information: jRCTs071180001.
Risk factors for short-term interval readmission after radical gastrectomy for gastric cancer: The merits of the home-health-care support over the readmission in gastric cancer.
Authors: Jeon Chul Hyo , Song Kyo Young 
Published: January 2022

263 Background: Readmission that occurs within a short period after discharge of initial gastrectomy for gastric cancer may affect the patient's prognosis and adversely affect the overall treatment courses. Among the possible related factors, the Influence between postoperative home-health-care support and readmission has been studied in various diseases, but the relationship with gastric cancer patients was limited. The purpose of the study was to investigate the risk factors associated with readmission after gastrectomy and home-health-care support on readmission. Methods: A total of 2,605 patients who underwent curative gastrectomy with lymphadenectomy between 2013 and 2020 were retrospectively reviewed. Chi-squared tests were performed to evaluate for potential risk factors for readmissions. A multivariate regression analysis was performed to identify independent predictors, including home-health-care support. Results: Among 2,605 undergoing gastrectomy, 134 (5.18%) had suffered unplanned readmission within postoperative 60-days (0̃50days). There was no significant annual difference in the postoperative length of hospital stay and the proportions of the home-health-care support during the study period, but the readmission rate decreased significantly by 0.646% annually from 7.88% in 2013 to 1.22% in 2020 (P = 0.023). The readmission group had a higher Eastern Cooperative Oncology Group (ECOG) score, a significantly higher rate of open and total gastrectomy, and a higher rate of postoperative complications and severe postoperative complications (C-D grade≥3a). Multivariable analysis demonstrated that the occurrence of severe postoperative complications (odds ratio (OR) 9.306, p < 0.001) and the presence of home-health-care support (OR 1.725, p = 0.009) were independently associated with readmission. However, age, sex, ECOG, preoperative body mass index, preoperative comorbidity including cardiovascular comorbidity, surgery-related factors, and the disease severity had no significant effect on readmission. Among the significant factors, home-health-care support showed the effect of reducing the time span between the index discharge and readmission (p = 0.049) and the length of the second hospitalization (p = 0.029). Conclusions: Readmission after radical gastrectomy is affected by various factors. Among them, home-health-care support has the merits of reducing the length of hospital stay for readmission by identifying patients in need of hospitalization at an early stage through direct face-to-face contact with the patient. It is necessary to establish an appropriate strategy to improve the quality of postoperative courses for high-risk patients of readmission.
Comparative outcomes of minimally invasive and open gastrectomy.
Authors: Glasser Jamie , Schuster Cassandra , Huston Jamie , Shridhar Ravi , Meredith Kenneth Lee 
Published: January 2022

271 Background: Gastric cancer(GC) is associated with significant mortality worldwide. Radical gastrectomy with lymphadenectomy is considered the only curative option for GC. Laparoscopic(LG) and more recently robotic(RG) techniques have been developed as a way to potentially decrease the peri-operative morbidity associated with gastrectomy. We sought to compare oncologic outcomes with minimally invasive and open techniques for gastrectomy. Methods: Utilizing the National Cancer Database we identified patients with gastric cancer who underwent gastrectomy. We then stratified technique, RG, LG, or OG. Mann-Whitney U and Kruskal were used to compare continuous variables and Pearson’s Chi-square test was used to compare categorical variables. Unadjusted survival analyses were performed using the Kaplan-Meier method. Multivariate analysis (MVA) was performed to identify predictors of survival. A p < 0.05 was considered significant. Results: We identified 2,530 patients RG, 10,790 in the LG and 25,810 in the OG group with median ages of 66, 66 and 67 years respectively, p < 0.001. There were higher numbers of poorly differentiated tumors in the OG 60% compared to RG (49.7% and LG 49.1%, p < 0.001. Additionally, there were increased numbers of signet ring GC in the OG 16.7%, compared to 13.8% in the RG and 13.8% in the LG, p < 0.001. There were higher numbers of early stage GC’s in the RG and LG compared to more advanced stages (stage II and III in the OG), p < 0.001. RG and LG did demonstrate higher numbers of R0 resections 92.8% and 89.9% compared to OG at 85.2%, p < 0.001. Length of stay was shorter in the RG and LG at 7 (4-10) days compared to 8 days (6-12) in the OG cohort, p < 0.001. Thirty and 90-day mortality rates were higher in the OG (4.3% and 8.3%) compared to 2.1% and 4% in the RG and 2.7% and 5.4% in the LG patients. Median and 5-year survival was higher in the RG (84.7mo and 61%) and LG (90.3mo and 58%) compared to the OG at 48.3mo and 46%, p = 0.001. When adjusted by stage this survival benefit persisted across all stage cohorts (stage 0-1, p = 0.001, stage 2, p = 0.001, and stage 3, p = 0.001). Multivariate analysis revealed that age, sex, Charlson/Deyo score, tumor location, histology, grade, stage, facility volume, and neoadjuvant therapy were all predictors of survival. Conclusions: Robotic and laparoscopic approaches to gastrectomy demonstrate improved median and overall survival compared to conventional open approaches. This benefit was demonstrated across all stages.
Trends in long-term survival after liver resection for gastric cancer liver metastasis: Analysis of a single-center experience over 28 years.
Authors: Ito Hiromichi , Takemura Nobuyuki , Oba Atsushi , Ono Yoshihiro , Sato Takafumi , Inoue Yosuke , Saiura Akio , Takahashi Yu 
Published: January 2022

290 Background: While systemic chemotherapy for gastric cancer has evolved significantly in the last decade, the role of surgery for liver metastasis remained controversial. The aims of this study were to examine the trend in outcomes of patients with gastric cancer liver metastasis (GCLM) undergoing resection at our center, and to define the optimal selection criteria for resection. Methods: One hundred and twenty-two consecutive patients who underwent liver resection for GCLMs with curative intent at our institution from 1993 through 2021 were included. The patients were grouped into 2 eras: era I, 1993 to 2010; era II, 2011 to 2021. Our criteria for liver resection included absence of extrahepatic disease, and the limited number of liver metastasis (often 3 or less). Median follow-up was 34 months for all and 71 months for the survivors. Results: There were 63 patients in era I and 59 in era II. The patients in era II received chemotherapy prior to liver resection more often (68% vs 41%, p = 0.004), and their primary tumor was less advanced (T3/4; 66% vs 85%, p = 0.021) with less regional lymph node metastasis (median No. of positive nodes; 4 vs 1, p = 0.034) compared to those in ear I. Median and 5-year disease-specific survival (DSS) were better in era II (not reached, 55%) than in era I (35 months, 35%, p = 0.025). In the multivariate analysis for the entire cohort, elevated CEA (> 50 ng/ml), primary T4, and primary at the proximal stomach emerged as independent factors associated with shorter DSS. Number of these risk factors are highly predictive for long-term survival; among the patients without or with a single factor alone, 5-year DSS was 50%, whereas none of those with multiple risk factors survived beyond 5 years ( p< 0.0001). Conclusions: Long-term outcomes for patients with oligo-GCLM has improved in the modern chemotherapy era. Liver resection should be considered unless they carry multiple risk factors.