bluuebunny/crossref_metadata_2025_split huggingface dataset:
Total neoadjuvant therapy compared with standard therapy in locally advanced rectal cancer: A systematic review and meta-analysis.
Authors: Manthravadi Sashidhar , Sun Weijing , Saeed Anwaar , Baranda Joaquina Celebre , Kasi Anup 
Published: January 2019

709 Background: Standard therapy of locally advanced rectal cancer (LARC) includes concurrent chemoradiotherapy (CRT) followed by surgery and adjuvant chemotherapy (CT). An alternative strategy known as Total Neoadjuvant Therapy (TNT) involves administration of CRT and CT prior to surgery with the goal of delivering uninterrupted systemic therapy to eradicate micrometastases. A comparison of these two approaches has not been reviewed previously. Methods: Following PRISMA guidelines, a systematic review of PubMed and Web of Science was performed from inception through September 2018 to identify studies which compared TNT with CRT in LARC. The outcomes of interest were pathologic complete response rates (PCR), sphincter-preserving surgery rates, ileostomy rates, disease-free survival (DFS) and overall survival (OS). Summary hazard ratios (HR) with 95% confidence intervals (CI) were estimated using a random effects model and heterogeneity was estimated using the inconsistency index (I2). Results: After reviewing 2,163 reports, 5 studies which compared CRT and TNT were selected for inclusion. These were reported from Europe and the United States and included a total of 1,134 patients of whom 552 received TNT. The pooled prevalence of PCR was 32.4% (range 17-28%) in the TNT group and 22.3% (range 4-21%) in the CRT group. In a meta-analysis of five studies, TNT was associated with a higher chance of achieving a pathologic complete response (OR 1.92; 95% CI 1.44- 2.57, I2= 22%). Recipients of TNT also had higher odds of receiving sphincter-sparing surgery (5 studies, OR 1.92; 95% CI 1.44- 2.57, I2= 0%) and lower odds of requiring an ileostomy (2 studies, OR 0.72; 95% CI 0.54- 0.96, I2= 0%). Only one study presented data on DFS and noted improved DFS in patients who received TNT (OR 0.72; 95% CI 0.54- 0.96). The impact of TNT relative to standard therapy on overall survival was not reported. Conclusions: Total Neoadjuvant Therapy is a promising strategy in locally advanced rectal cancer, with superior PCR rates compared to standard therapy. However, the long term impact on disease recurrence and overall survival remain unclear. These are best be studied in a prospective randomized clinical trial.
Elucidating the pathogenesis of esophageal adenocarcinoma through meta-analysis of public data.
Authors: Khorfan Kamal , Aljabban Jihad , Syed Saad , Salhi Hussam , Adejare Aderinola , Suara Habeeb , Allarakhia Zahir , Panahiazar Maryam , Hadley Dexter 
Published: January 2019

71 Background: Esophageal adenocarcinoma (EAC) is the sixth most common cause of cancer-related deaths worldwide. It commonly arises in the setting of reflux disease and Barett’s esophagus. It remains incurable and holds a poor prognosis. Dissecting the genetic signature of EAC can pave new therapeutic avenues. Methods: We employed our Search Tag Analyze Resource (STARGEO) platform to conduct meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO). We tagged 151 tumor samples from EAC patients and 62 normal esophageal samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p < 0.05) and an absolute experimental log ratio greater than 0.15 between tumor and control. Results: Our analysis revealed granulocyte adhesion and diapedesis and FXR/RXR signaling as top canonical pathways. TGFB1, TNF, and beta-estradiol were top upstream regulators with predicted activation. TGFB1 and TNF expression have been correlated with poor prognosis in EAC. Also, beta-estradiol has tumorigenic activity in several cancers but has not been investigated in EAC. Among the top upregulated genes were oncogenic genes such as tetraspanin 8, the antiapoptotic factor OLFM4, and the protease cathepsin E (CTSE). SPINK1, a trypsin inhibitor with recently suggested role in cancer, and the choline transporter SLC44A4, a drug target for pancreatic cancer, were also upregulated. The most downregulated genes included alcohol dehydrogenase 7, associated with EAC in alcohol-drinkers, and the pro-apoptotic gene CRCT1. We also found downregulation of the serine peptidase inhibitor SPINK7. SPINK7 is involved in maintaining epithelial-barrier integrity and is implicated in eosinophilic esophagitis pathogenesis. Lastly, there was downregulation of the candidate tumor suppressor gene transglutaminase 3. Conclusions: Despite screening efforts, EAC incidence and mortality continues to increase as does the need for better treatment. This meta-analysis defines the significant gene expression changes within causal disease processes to provide markers for detection, prognostic insight, and therapeutic value for EAC.
Nodal retrieval and short-term outcomes of robotic and laparoscopic colectomies for colon cancer.
Authors: Nguyen Trang , Stern Stacey , Dehal Ahmed , Vuong Brooke , Bilchik Anton J. 
Published: January 2019

713 Background: It is debatable whether robotic colectomies is advantageous over laparoscopic colectomies for colon cancer (CC). We aim to evaluate oncologic and perioperative outcomes between robotic and laparoscopic colectomies in a national database. Methods: The National Cancer Database was queried from 2010-2014 for patients with resectable (stage I-III) CC. Lymph node (LN) retrieval, length of stay (LOS), perioperative outcomes and OS were analyzed based on type of surgery: right colectomy vs. left colectomy and robotic (ROBO) vs. laparoscopic (LAP). Results: 61,903 patients met inclusion criteria. There was no difference in inadequate LN retrieval (< 12 LN), or short-term mortality between ROBO and LAP groups. There was a significant decrease in conversion to an open operation and LOS for ROBO vs. LAP groups as well as increased 5 year OS (Table). ROBO colectomies increased four-fold over 5 years. About half were done at community hospitals (56%) and at low ROBO volume hospitals (47.2%). Inadequate LN retrieval in the ROBO group was greater at low volume centers (9.2%) compared to high volume centers (12.3%) (p < 0.0001) as well as at community hospitals (12.2%) compared to academic hospitals (8.5%) (p=0.0003). Conclusions: This population analysis showed that robotic colectomies was associated with equivalent short-term outcomes and LN retrieval as laparoscopic colectomies. However, half of robotic colectomies were done at community hospitals or low volume hospitals, where the rate of inadequate LN retrieval was higher than at academic hospitals or high volume centers. As robotic colectomies increases, it is important that technology is implemented judiciously so that oncologic outcomes are not compromised. [Table: see text]
Pelvic radiotherapy in combination with radical resection of the primary tumor improves survival in patients with metastatic rectal adenocarcinoma: A national cancer database analysis (NCDB).
Authors: Renz Paul B. , Hasan Shaakir , Wegner Rodney E , Finley Gene Grant , Monga Dulabh K. , Raj Moses S. , McCormick James , Kirichenko Alexander V. 
Published: January 2019

714 Background: With recent advances in systemic therapies and increased survival of patients with metastatic rectal cancer, the role of primary tumor resection may be of increased importance and is often debated. However, the role of combining radiotherapy to surgical resection in the metastatic setting is unknown. Accordingly, we utilized the NCDB to quantify survival in metastatic rectal adenocarcinoma patients with primary tumor resection with and without pelvic radiotherapy. Methods: Of the 15,643 Stage IV rectal adenocarcinoma patients receiving chemotherapy from 2004 to 2014, 4051 patients had primary tumor resection with sufficient follow up for analysis. Patients were stratified by receipt of pelvic radiotherapy (n = 1882) or no pelvic radiotherapy (n = 2169). Univariable/multivariable analyses and propensity-adjusted Cox proportional hazard ratios for survival were performed. Results: Median age was 63 years (18-90) with median follow up of 32.3 months (3.02-151.29). There were more patients with T3/T4 disease (69.6% vs 46.5%) or N1 disease (41.5% vs 27.3%) in the surgery plus radiotherapy arm. Metastatic burden was confined to one organ in 40.5% of patients and was equally distributed between radiotherapy and non-radiotherapy groups (OR 0.92; 95%CI 0.81-1.04). Median survival was 46.3 months vs. 35.3 months in favor of adding radiotherapy (p < 0.001). The 2, 5 and 10-year overall survival were 68.4%, 24.8%, and 9.5% for surgical resection alone compared to 77.2%, 39.6%, and 22.3% for surgery + radiotherapy. On multivariable analysis radiotherapy was associated with a statistically significant reduction in the risk of death (HR 0.718; 95% CI 0.661-0.780). This benefit was upheld on propensity matched analysis (HR 0.722; 95% CI 0.0665-0.784). Conclusions: Our study indicates that adding radiotherapy to surgical management of the primary tumor in patients receiving systemic chemotherapy for metastatic rectal adenocarcinoma improves survival. Prospective investigation of the management of the rectal primary tumor with chemotherapy, pelvic radiotherapy, and surgical resection is warranted.
Patterns of care and outcomes of low-lying adenocarcinoma and squamous cell carcinoma of the rectum.
Authors: Adedoyin Paul , Lee Anna , Malakhov Nikita , Kavi Ami , Sheth Niki , Garay Elizabeth , Schreiber David 
Published: January 2019

715 Background: To analyze the patterns of care and survival for stage I-III squamous cell (SCC) and adenocarcinoma (AC) of the rectum from 2004-2015 based on receipt of surgery alone (S), neoadjuvant chemoradiation followed by surgery (CRT+S), surgery followed by adjuvant chemoradiation (S+CRT) and definitive chemoradiation (CRT). Methods: The NCDB was explored to identify patients diagnosed with low-lying stage I-III AC and SCC of the rectum from 2004-2015 who received S, CRT+S, S+CRT or CRT. Frequency distributions between the categorical variables were compared using the Chi-square test. Overall survival data and Kaplan-Meier curves were compared via the log-rank test stratifying the groups (AC vs. SCC) by stage and treatment. Cox proportional hazards regression models were performed to assess for covariates that had an impact on survival. Results: There were 22,227 patients included in this study, from which 21,587 (97.1%) were AC and 640 (2.9%) were SCC. Median follow-up for the entire cohort was 54 months. The median RT dose for AC was 5040 cGy and for SCC 5400 cGy. 5-year OS of AC vs. SCC in the entire cohort was 61.6% vs. 56.1%, respectively (p<0.001). The OS for AC was 51.5% for S alone, 71.1% for CRT+S, 65.6% for S+CRT, and 36.2% for CRT (p<0.001). The OS for SCC was 49.2% for surgery alone, 54.2% for CRT+S, 67.1% for S+CRT, and 65.7% for CRT (p=0.227). On multivariable Cox regression for AC, patients who received CRT+S (HR 0.61, p<0.001) or S+CRT (HR 0.67, p<0.001) had improved survival compared to S alone while those who had definitive CRT (HR 1.55, p<0.001) had worse survival. Conclusions: This is the largest case series of rectal SCC in the literature to date. Analysis suggests that SCCs of the rectum are more often treated with definitive CRT but are associated with slightly worse survival than adenocarcinoma, suggesting that perhaps surgery may need an increased utilization in this disease. [Table: see text]
FGFR2-altered gastroesophageal adenocarcinomas (GEA) are a rare clinicopathologic entity with a distinct genomic landscape.
Authors: Klempner Samuel Jacob , Madison Russell , Ross Jeffrey S. , Miller Vincent A. , Ali Siraj Mahamed , Schrock Alexa Betzig , Lee Jeeyun , Kim Seung Tae , Chao Joseph 
Published: January 2019

72 Background: Therapies directed at receptor tyrosine kinases (RTKs) in GEA have met with limited success. The small molecule FGFR2 inhibitor AZD4547 failed in a phase II biomarker-selected trial, though activity has been seen with FGFR2-directed strategies, including monoclonal antibodies. Despite observed activity, very little is known about the genomic landscape of FGFR2-altered GEA. Using a large genomic database, we sought to examine the classes of FGFR2 alterations and frequency of co-occurring alterations in GEA. Methods: 6,667 tissue specimens from unique patients with advanced GEA were assayed using hybrid capture-based comprehensive genomic profiling (CGP). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 95 or 114 loci. Descriptive statistics were used to compare among subgroups. Results: We identified a total of 269 (4.0%) FGFR2-altered cases consisting of FGFR2 amplified (amp; 209, 78% of FGFR2-altered), FGFR2 mutated (mut; 40, 15%) and FGFR2 rearranged (re, 37, 14%). There was a female predominance in FGFR2-altered cases (M:F = 1.6:1) vs FGFR wild-type (WT) (2.8:1). Cases with FGFR2amp and FGFR2re were exclusively MS-stable. The most common fusion partner was TACC2 (22%). FGFR2amp GEA had higher rates of TP53 mutation versus either FGFR2re of FGFR2mut cases (p = 4.4E-6). Co-occurring alterations in the other GEA RTK targets including ERBB2 (10%) , EGFR (8%) and MET (3%) were observed in all types of FGFR2-altered GEA. Co-occurring downstream alterations in MYC (17%), KRAS (10%) and PIK3CA (5.6%) were observed frequently in each class of FGFR2-altered GEA. The median TMB for FGFR2-altered GEA was 3.6 mut/mb, which was not significantly different from a median of 4.3 mut/mb seen in FGFR2 WT samples (p = 0.53). Conclusions: FGFR2-altered GEA is a heterogenous subgroup with approximately 20% of FGFR2-altered samples harboring concurrent RTK alterations. Putative co-occurring modifiers of FGFR2 directed therapy including oncogenic MYC, KRAS, PIK3CA alterations were also frequent, suggesting that pre-treatment CGP and combination approaches may be needed to optimize patient selection.
Long-term outcome of laparoscopic versus open total gastrectomy for advanced gastric cancer: A propensity score-matched analysis.
Authors: Lee Hayemin , Lee Junhyun 
Published: January 2019

77 Background: Laparoscopic total gastrectomy (LTG) for advanced gastric cancer (AGC) is technically and oncologically challenging procedure for surgeons. The aim of this study is to compare technical safety and long-term oncologic feasibility of LTG for AGC patients compared to open total gastrectomy (OTG) using propensity score (PS)-matched analysis. Methods: Between 2004 and 2014, 185 patients (OTG: 127, LTG: 58) underwent total gastrectomy due to advanced gastric cancer. PS-matching was done using patients’ age, sex, American Society of Anesthesiologist (ASA) physical status, extent of lymph node dissection, presence of combined resection and pathological stage of gastric cancer. Comparisons were made based on surgical outcomes and long-term survival rates. Results: After PS-matching, 102 patients, respectively 51 patients for each group, were enrolled. LTG had longer tumor-free proximal resection margin (OTG 2.5 cm vs. LTG 3.0 cm, p = 0.008). Total number of retrieved lymph node and metastasized lymph node was similar in both groups. The retrieved number of lymph nodes around splenic hilum (#10 and #11d) was similar in both groups (p = 0.105). Longer operation time was required in LTG (OTG 240 min. vs. LTG 320 min, p = 0.002) but less intraoperative bleeding was observed in LTG (OTG 390 cc vs. LTG 276 cc, p < 0.001). Patients of LTG were discharged earlier than OTG (OTG 12 days vs. LTG 10 days, p = 0.043). Overall morbidity and mortality of both group was similar. Between two groups, there was not a difference in 5-year overall survival rate (OTG 56.3% vs. LTG 56.5%, p = 0.597) or disease free survival rate (OTG 59.0% vs. LTG 67.6%, p = 0.455). Conclusions: For treating proximal AGC, LTG may be a technically and oncologically safe and feasible method.
The impact of neoadjuvant chemoradiation versus chemotherapy on short and long-term outcomes among gastric carcinoma patients.
Authors: Azab Basem , Macedo Francisco Igor , Picado Omar , Franceschi Dido , Livingstone Alan S , Yakoub Danny 
Published: January 2019

78 Background: There is little consensus on the use of neoadjuvant chemoradiation (NCRT) versus neoadjuvant chemotherapy (NCT) in gastric carcinoma (GC) patients. We sought to compare the outcomes of these two approaches in a large national data base. Methods: National Cancer Data Base PUF (2004-2014) of GC patients who underwent NCRT/NCT followed by resection were included. Primary outcome was overall survival (OS), secondary outcomes were pathological complete response (pCR), R0 resection and postoperative mortality. Results: A total of 4204 GC patients with NCT were included, 62% of them had additional neoadjuvant radiotherapy (NRT). NCRT had higher pCR and R0 rates [551/2613 (21%), 2314/2561 (90%)] than NCT group [148/1573 (9%), 1242/1543 (80%)], p < 0.0001. Multivariate logistic regression showed similar higher odds of pCR (OR 2.8, 95% CI 1.65-4.60, p < 0.0001) and R0 (OR 1.5, 95% CI 1.14-1.99, p = 0.004) among NCRT versus NCT. There was no significant difference in length of hospital stay, 30-day readmission rate, 30- and 90-day postoperative mortality. Median, 3- and 5-year OS for NCRT versus NCT were: (20.4 months, 24% and 11%) versus (18.3 months, 19% and 6%), p < 0.001. Univariate cox regression analysis showed superior OS with NRT (HR 0.9, 95% CI 0.80-0.91, p < 0.001). After adjusting for confounding variables, pCR (HR 0.2, 95% CI 0.18-0.24, p < 0.001) and R0 (HR 0.7, 95% CI 0.61-0.75, p < 0.001) had better OS, while NRT was not. Conclusions: NRT improved pCR and R0 rates in GC without increase in surgical morbidity/mortality. The long-term OS benefit of NRT is likely secondary to higher pCR and R0 resection.
The value of lymphadenectomy in esophageal cancer after neoadjuvant chemoradiation.
Authors: Azab Basem , Macedo Francisco Igor , Picado Omar , Ripat Caroline , Franceschi Dido , Livingstone Alan S , Yakoub Danny 
Published: January 2019

79 Background: There are conflicting reports on the value of the extent of post neoadjuvant chemoradiation (NCRT) lymphadenectomy (LND) in locally advanced esophageal adenocarcinoma (E-ADC) and squamous cell carcinoma (E-SCC). We sought to study the impact of LND variables [positive and total lymph node (LN) number and LN ratio (LNR)] on oncological outcomes in these patients. Methods: The National Cancer Data Base 2004-2014 was queried for patients with NCRT followed by esophagectomy. The median examined LN number was used to divide the patients into a higher (> 12) and lower (≤ 12) LND groups. The primary outcome was overall survival (OS) and secondary outcomes were 30- and 90-day postoperative mortality. Results: A total 4708 patients were included. The median of positive, negative LN, and LNR were and (0, 11, 0%). The median and 5-year OS for higher LND group were higher than the lower LND group (39 vs. 32 months, 38% vs. 34%), p < 0.0001. OS was not significantly different among E-SCC subset or among those who achieved pathological complete response (pCR). The higher LND group had better 30- and 90-day postoperative mortality rates (61/2335 = 2.6%, 141/2308 = 6.1%) than lower LND group (86/2262 = 3.8%, 184/2251 = 8.2%), p = 0.01 and 0.001, respectively . In multivariate Cox regression analysis, higher LND group (HR 0.88, 95% CI 0.81-0.96, p = 0.004) and LNR (per 10% increase: 1.11, 95% CI 1.09-1.13, p < 0.0001) were significant predictor of OS. Conclusions: The LND (> 12 examined LN) remains as a crucial treatment goal after NCRT with potential survival benefit, especially among E-ADC and those did not achieve pCR.
Prognostic factor analysis in third-line chemotherapy for elderly patients with metastatic gastric cancer.
Authors: Hasegawa Hiroko , Iwasaki Tetsuya , Ishihara Akio , Sakakibara Yuko , Akasaka Tomohumi , Nakazuru Shoichi , Ishida Hisashi , Hirao Motohiro , Mita Eiji 
Published: January 2019

82 Background: Recently, the proportion of elderly patients (pts) with metastatic gastric cancer (mGC) has increased in Japan. Survival benefits of salvage treatment after second-line chemotherapy (CTX) for mGC were shown in several prospective studies. However, the role of salvage treatment in elderly pts remains controversial. Methods: We reviewed 185 pts with mGC who received palliative CTX aged ≥ 70 years at our institution between April 2007 and March 2018. Eligibility criteria were as follows: PS 0-2, refractory to first-line and second-line CTX. The purpose of this study was to evaluate the clinicopathologic factors that affected overall survival for elderly pts with mGC, univariate and multivariate analyses were performed on the baseline factors at the beginning of third-line CTX. Results: Of all, 71 pts were eligible. Median age was 75 years (71-85). Median progression-free survival (PFS) and overall survival (OS) for third-line CTX were 3.2 and 7.5 months, respectively and an overall response rate and disease control rate were 4.2% and 43.7%, respectively. In univariate analysis, the following four factors were identified to have prognostic significance: performance status (PS) (ECOG 0–1 or 2), serum albumin level (< 3.5 or ≥ 3.5 g/dl), serum LDH level (≤ 240 or > 240 IU/l), PFS under second-line CTX (< 3 or ≥ 3 months). Multivariate analysis found three prognostic factors affecting poor survival following third-line CTX: PS of 2 (hazard ratio (HR) 8.89, 95% confidence interval (CI) 3.99–20.2; P = 0.001), serum LDH level > 240 IU/l (HR 2.75, 95% CI 1.48–5.05; P = 0.002) and median PFS under second-line CTX of < 3 months (HR 1.89, 95% CI 1.01–3.43; P = 0.045). A prognostic index was constructed, dividing pts into low- (0 factor), intermediate- (1-2 risk factors), or high- (3 risk factors) risk groups. Median OS for each group were 12.6, 6.0 and 3.0 months, respectively ( P < 0.001). Conclusions: This analysis suggests that some clinicopathologic factors might be helpful in identifying the subgroup of elderly pts most likely to benefit from third-line CTX for metastatic gastric cancer.