bluuebunny/crossref_metadata_2025_split huggingface dataset:
How do social determinants of health impact timeliness of chemotherapy and survival in patients with metastatic colon cancer? A 12-year study.
Authors: Jayakrishnan Thejus Thayyil , Bakalov Veli , Chahine Zena , Finley Gene Grant , Monga Dulabh K. , Wegner Rodney E. 
Published: February 2020

36 Background: Studies have demonstrated disparities in health care driven by socioeconomic factors. Patients with metastatic cancer represent the most vulnerable group of cancer patients. We hypothesized that these factors impact timeliness to chemotherapy in patients with metastatic colon cancer and their treatment outcomes. Methods: We queried the National Cancer Database (NCDB) for patients with metastatic colon cancer (AJCC pathologic stage4) diagnosed from 2004-2016. We selected patients treated with chemotherapy as first line treatment within 90 days of diagnosis. Time to initiation (TTI) was defined as time in days (d) from diagnosis of cancer to initiation of systemic chemotherapy and survival was measured in terms of months (m) from the day of diagnosis. Stepwise negative binomial regression and Cox proportional hazard models were used for analysis. Results: We identified 11,764 patients meeting the eligibility criteria. Median age was 62 (range 18-90) years and included 51% males. Median TTI was 9d (range 1-89) and median overall survival was 24.3m. TTI was significantly associated with race - Caucasian 26.4d (95% CI 25.6-27.1) vs. African American 28.9d (26.9-31.0) p-value=0.021, Median income - ≥ $63,000 23.5d (95% CI 22.4 – 24.5) vs.< $38,000 29.2d (27.3 – 31.0) p-value < 0.0001, Facility type – Community cancer center 23.6d (95% CI 21.6-25.6) vs. Academic/research program 26.5d (95% CI 25.5 – 27.4) p-value=0.014. Factors impacting survival in a multivariate model included time to chemotherapy initiation – 24.7m with TTI ≤ 9d vs. 23.8m with TTI > 9d (p-value <0.0001), type of facility – Academic/research program 26.4m vs. community cancer center 21.3 (p-value <0.0001), age (p-value <0.001), comorbidities (p-value <0.0001) and site of primary. Conclusions: Patients with metastatic cancer are not free from disparities driven by social determinants of health that impact their outcomes. The findings suggest that further studies to identify barriers to healthcare access and continued efforts to improve them are warranted.
A phase I/II multisite study of nivolumab and carboplatin/paclitaxel with radiation therapy (RT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC).
Authors: Wu Jennifer J. , Atkinson Emily Catherine , Leichman Lawrence P. , Patel Hitendra , Iqbal Syma , Du Kevin Lee , Bizekis Costas , Goldberg Judith D. , Thomas Charles R. , Cohen Deirdre Jill , Becker Daniel Jacob , Siolas Despina , Beri Nina , Oberstein Paul Eliezer , Ku Geoffrey Yuyat 
Published: February 2020

372 Background: Preoperative chemoRT is a standard-of-care as shown in the CROSS trial ( N Engl J Med 2012;366:2074-2084), Surgery is sometimes deferred in pts with clinical CR (cCR) based on lack of overall survival benefit ( J Clin Oncol 2005;23:2310-2317, J Clin Oncol 2007;25:1160-1168). Nivolumab has activity in advanced ESCC ( Lancet Oncol 2017;18:631-639), and adding it to chemoRT may improve outcomes. Methods: This phase I/II study was designed to assess the safety and tolerability and efficacy of nivolumab added to chemoRT (6 weekly carboplatin AUC 2, paclitaxel 50mg/m2, RT 50.4 Gy in 1.8 Gy fractions 5/7 days) for pts with TanyN1-3 or T3-4N0M0 ESCC. The phase I primary endpoint is “unacceptable toxicity” at 28 days after the last dose of chemotherapy. The phase II primary endpoints are cCR (endoscopy + PET/CT) and pCR rates for pts undergoing surgery. Nivolumab is given q2W ×2, then concurrent chemoRT with nivolumab q2W x3. If no cCR, pt proceeds to esophagectomy, then adjuvant nivolumab q2W ×3; if cCR, pt has an option of no surgery but receives nivolumab q2W ×3. Results: From 7/20/17 to 12/27/18, 6 pts were enrolled. No unacceptable or grade 5 toxicities were observed. The most common grade 1/2 AEs in >1 pt were anorexia, myelosuppression, elevated AST and nausea. Grade 3/4 AEs in >1 pt were lymphopenia and leukocytopenia. 2 pts required hospitalizations (dyspnea 1, colitis 1). All pts completed therapy; 1 pt had dose delay due to grade 2 esophagitis; 2 pts progressed, 4 achieved cCR. Of 4 pts with cCR, 2 pts chose surgery and both achieved pCR. None of the 4 pts recurred. Conclusions: ChemoRT with nivolumab is tolerable with manageable toxicities in locally advanced ESCC. Enrollment to the phase II portion ended because of slow accrual. Adverse Events. Grade 1 &2 in > 1 pt: 4/6: Anorexia & Anemia 3/6: Leukocytopenia Neutropenia Thrombocytopenia Nausea & Elevated AST 2/6: Hypomagnesemia Hypokalemia Grade 3 & 4 in > 1 pt: 5/6: Lymphopenia, 2/6: Leukocytopenia
Laparoscopic versus open total gastrectomy for clinical stage I gastric cancer: Morbidity and mortality results from a prospective randomized multicenter controlled trial (CLASS02).
Authors: Liu Fenglin , Huang Changming , Xu Zekuan , Su Xiangqian , Zhao Gang , Ye Jianxin , Du Xiaohui , Huang Hua , Hu Jiankun , Li Guoxin , Yu Peiwu , Li Yong , Suo Jian , Zhao Naiqing , Zhang Wei , Li Haojie , He Hongyong , Sun Yihong ,   Chinese Laparoscopic Gastrointestinal Surgery Study Group
Published: February 2020

378 Background: The safety of laparoscopic total gastrectomy (LTG) for the treatment of gastric cancer remains lack of clinical evidence. The aim of this study was to compare the safety of LTG for clinical stage I gastric cancer with the conventional open total gastrectomy (OTG). Methods: From January 2017 to September 2018, a total of 227 patients with clinical stage T1N0-1M0/T2N0M0 gastric cancer were enrolled in this clinical trial and randomly assigned to Laparoscopic Gastrectomy group (LG, n=113) or Open Gastrectomy group (OG, n=114). The morbidity and mortality within 30 days following surgery, the recovery course, and the postoperative hospital stay between LG group (n=105) and OG group (n=109) were compared. Clavien-Dindo classification system was used to stratify surgical complications. Results: The overall morbidity rate was not significantly different in each group (LG group: 19.05%; OG group: 20.18%; Rate difference [RD]: -1.14%, 95%CI, -11.75%-9.58%). Intraoperative complications occurred in 3 (2.86%) patients in LG group and 4 (3.67%) patients in OG group (RD: -0.81%, 95%CI, -6.52%-4.85%). In addition, there was no significant difference in the overall postoperative complication rate of 18.10% in LG group and 17.43% in OG group (RD: 0.66%, 95%CI, -9.61%-11.01%). Each subtypes of postoperative complication were not significantly different between groups. One patient in LG group died of intra-abdominal bleeding from splenic artery, and there was no significant difference in mortality between LG group and OG group (RD: 0.95%, 95%CI, -2.54%-5.20%). The distribution of severity was similar between the two groups. Conclusions: Experienced surgeons can safely perform LTG with lymphadenectomy for clinical stage I gastric cancer. Clinical trial information: NCT03007550.
Immune-related adverse events and neutrophil-to-lymphocyte ratio are possible predictive factors for gastric cancer treated with nivolumab.
Authors: Eda Hirotugu , Tozawa Katsuyuki , Nakamura Kumiko , Kondo Takashi , Tomita Toshihiko , Oshima Tadayuki , Fukui Hirokazu , Miwa Hiroto 
Published: February 2020

385 Background: The Immune-related adverse events (irAEs) and neutrophil-to-lymphocyte ratio (NLR) are effective as a predictive factor for lung cancer treated with nivolumab The objective of this study was to determine the effectiveness of irAEs and NLR for patients with advanced gastric cancer (AGC) treated with nivolumab. Methods: This was a retrospective study of patients with AGC treated with nivolumab from October 2017 to August 2019. The NLRs were calculated before the first cycle. Results: Forty patients were enrolled (males 29, females 11) with a median age of 65 years. The overall response rate was 12.5%. The median PFS was 4.2 months (range, 0.5 - 21). Stratified with high NLR (≥5) and low NLR ( < 5), the median PFS was shorter in the high NLR arm (1.1 vs. 5.1 months; p = 0.0003). irAEs were observed in 5 of the 40 study patients (12.5%), including 1 patients (20%) with such events of grade 3 or 4, and 1 patient requiring systemic corticosteroid therapy. Median PFS was 6.5 months (95% CI, 4.4 to not reached [NR]) and 3.9 months (95% CI, 3.0 to 7.5) (P = .09) for patients with or without irAEs, respectively. Conclusions: NLR may be an effective prognostic factor in patients with AGC treated with nivolumab. Development of irAEs was associated with survival outcome of nivolumab treatment in patients with AGC. Further studies are needed to confirm our findings.
Concurrent versus sequential neoadjuvant chemoradiation therapy for esophageal and gastroesophageal junction adenocarcinoma.
Authors: Torphy Robert J. , Ho Felix , Friedman Chloe , Leong Stephen , Wani Sachin , Scott Christopher D. , Weyant Michael J. , Meguid Robert A. , Gleisner Ana , Goodman Karyn A. , McCarter Martin D. 
Published: February 2020

395 Background: Neoadjuvant therapy is the standard of care for locally advanced esophageal and gastroesophageal junction (GEJ) adenocarcinoma, with most patients receiving neoadjuvant chemoradiation (CRT). CRT can be delivered concurrently or sequentially after induction chemotherapy. The purpose of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) among patients who received concurrent versus sequential CRT in the National Cancer Database (NCDB). Methods: Patients who received neoadjuvant CRT and underwent curative intent esophagectomy for esophageal or GEJ adenocarcinoma from 2006-2015 were included. Patients with clinical T4 or metastatic disease were excluded. Concurrent CRT was defined as radiation treatment starting within 6 weeks of chemotherapy start. Sequential CRT was defined as radiation treatment starting greater than 6 weeks after chemotherapy start. Propensity weighting was conducted to balance patient, disease, and facility covariates between groups. Results: 12,460 patients met inclusion criteria. 11,880 (95%) patients received concurrent CRT and 580 (5%) patients received sequential CRT. Patients who received sequential CRT were significantly younger (mean age: 60.7 vs 62.2 years), had higher clinical nodal stage (N2-3: 14.7% vs 10.1%), and were more often treated at academic/research hospitals (67.1 vs 55.5) (all p≤0.001). pCR was achieved in 16.2% of patients who received sequential CRT and in 14.0% of patients who received concurrent CRT (p = 0.131). Following propensity weighting, OS was significantly improved among patients who received sequential versus concurrent CRT (HR 0.82; 95% CI 0.74-0.92; p < 0.001) with a median OS for the sequential cohort of 41.4 months versus 29.4 months for those who received concurrent CRT. Conclusions: In this retrospective study from a large national database of patients who received neoadjuvant CRT for esophageal and GEJ adenocarcinoma, sequential CRT is associated with a significant OS benefit. These results merit consideration of a well powered prospective multi-institutional randomized clinical trial to further evaluate this observed difference.
Safety of perioperative atezolizumab in combination with FLOT versus FLOT alone in patients with resectable esophagogastric adenocarcinoma: An interim safety analysis of the DANTE, a randomized, open-label phase II trial of the German Gastric Group at the AIO and the SAKK.
Authors: Al-Batran Salah-Eddin , Lorenzen Sylvie , Schenk Michael , Thuss-Patience Peter C. , Goekkurt Eray , Hofheinz Ralf , Kretzschmar Albrecht , Bolling Claus , Angermeier Stefan , Wicki Andreas , Siebenhuener Alexander Rheinhard , Eigendorff Ekkehard , Pink Christin , Ettrich Thomas Jens , Schmalenberg Harald , Waberer Lisa , Talbot Jonathan , Pauligk Claudia , Goetze Thorsten Oliver , Homann Nils 
Published: February 2020

398 Background: The DANTE study evaluates atezolizumab in the perioperative treatment of locally advanced, potentially resectable gastric or GEJ adenocarcinoma in combination with perioperative FLOT. Here, we report the protocol-defined interim safety analysis. Methods: DANTE is a large, multinational, prospective, multicenter, randomized, investigator-initiated, open label phase II trial. Patients (pts) with locally advanced, potentially resectable adenocarcinoma of the stomach and GEJ (≥cT2 and/or N-positive) without distant metastases are enrolled. Pts are randomized 1:1 to 4 pre-operative 2-week cycles (8 weeks) of FLOT followed by surgery and 4 additional cycles of FLOT plus atezolizumab at 840 mg every 2 weeks, followed by a total of 8 additional cycles of atezolizumab at 1200 mg every 3 weeks as monotherapy (arm A) or FLOT alone (arm B). Primary endpoint is time to disease progression or relapse after surgery (PFS/DFS). Results: Recruitment started in Sept 2018; by September 2019, a total of 122 pts have been randomized. This analysis is based on the first 40 pts (20 pts in each arm). The pts had a median age of 62 y and 75% of pts had an ECOG PS of 0 in both arms. The cohort was well balanced in terms of tumor location and clinical stage. 90% of pts enrolled completed all pre-operative cycles in each arm. Total number of adverse events with relation to study treatment was 154 in arm A and 148 in arm B. Total number of serious adverse events (SAE; related or not) was 16 in Arm A and 14 in arm B. 20% of pts in each arm had an SAE due to perioperative morbidity. No surgical mortality was observed. 18 and 19 pts proceeded to operation in arms A and B, respectively. Premature treatment discontinuation occurred in 2 pts in each arm: disease progression (1) and deterioration of general health condition (1) in arm A; and pts’ wish (1) and death (1) in arm B. Median hospitalization time was 15 days in arm A and 16 days in arm B. Conclusions: perioperative atezolizumab plus FLOT is feasible and safe. The study continued recruitment. Clinical trial information: NCT03421288.
Implications of postoperative complications on survival after cytoreductive surgery and HIPEC: A multi-institutional analysis of the United States HIPEC Collaborative.
Authors: Gamboa Adriana C. , Lee Rachel M. , Turgeon Michael K. , Ahmed Ahmed , Grotz Travis Edward , Fournier Keith F. , Dineen Sean Patrick , Veerapong Jula , Clarke Callisia , Mogal Harveshp , Patel Sameer H. , Lambert Laura A. , Abbott Daniel Erik , Raoof Mustafa , Johnston Fabian McCartney , Cloyd Jordan , Maithel Shishir K. , Staley Charles A. 
Published: February 2020

40 Background: Postoperative complications (POCs) are associated with worse oncologic outcomes in various cancer histologies. The impact of POCs on the survival of patients with appendiceal or colorectal cancer after cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC) is unknown. Methods: US HIPEC Collaborative (2000-17) was reviewed for patients who underwent CCR0/1 CRS/HIPEC for appendiceal/colorectal cancer. Analysis was stratified by non-invasive appendiceal neoplasm vs invasive appendiceal/colorectal adenocarcinoma. POCs were grouped into infectious, cardiopulmonary, thromboembolic and intestinal dysmotility. Primary outcomes were 3-yr overall survival (OS) and recurrence-free survival (RFS). Results: Of 1304 pts, median age was 55 yrs, 41% were male (n = 537), 33% had non-invasive appendiceal (n = 426) and 67% had invasive appendiceal/colorectal adenocarcinoma (n = 878). In the non-invasive appendiceal cohort, POCs were identified in 55% (n = 233) and OS and RFS did not differ between patients who experienced a complication and those who did not (OS 94 vs 94% p = 0.26; RFS 68 vs 60% p = 0.15). In the invasive appendiceal/colorectal adenocarcinoma cohort, however, POCs (63%; n = 555) were associated with decreased OS (59 vs 74% p < 0.001) and RFS (32 vs 42% p < 0.001). Infectious POCs were most common (35%; n = 196). On MV analysis accounting for gender, PCI and incomplete resection (CCR1), infectious POCs in particular were associated with decreased OS compared to no complication (HR 2.08 95%CI 1.48-2.93 p < 0.01) or other types of complications (HR 1.7 95%CI 1.28-2.25 p < 0.01). This association persisted for infectious POCs and reduced RFS (HR 1.61 95%CI 1.23-2.10 p < 0.01). Conclusions: Postoperative complications are associated with decreased OS and RFS after CRS/HIPEC for invasive histology, but not for an indolent disease like non-invasive appendiceal neoplasm. Of all complication types, infectious complications are the main driver for this association. The exact mechanism is not known, but may be immunologic. Efforts must target best practices and standardized prevention strategies to minimize infectious POCs.
Cytoreductive surgery in selected patients with metastatic gastric cancer treated with systemic chemotherapy.
Authors: Berger Yaniv , Schuitevoerder Darryl , Vining Charles Christian , Giurcanu Mihai , Posner Mitchell C. , Roggin Kevin K. , Polite Blase N. , Liao Chih-Yi , Eng Oliver , Catenacci Daniel V.T. , Turaga Kiran 
Published: February 2020

409 Background: Cytoreductive surgery (CRS – gastrectomy combined with metastasectomy) for non-palliative indications is controversial for patients with metastatic gastric adenocarcinoma (MGA). We hypothesized that CRS in addition to systemic chemotherapy is associated with an improved survival when compared to patients with MGA receiving chemotherapy alone. Methods: Patients with MGA who received systemic chemotherapy between 2004-2016 were identified using the National Cancer Database (NCDB). Nearest neighbor 1:1 propensity score matching of demographic, tumor-related and treatment-related factors was used to create comparable groups. Overall survival (OS) was compared between subgroups using Kaplan-Meier analyses. Immortal bias analysis was performed among those that survived at least 90 days. Results: We identified 29,728 chemotherapy-treated patients who were divided into 4 subgroups: No surgery (NS, n = 25,690), metastasectomy alone (n = 1170), gastrectomy alone (n = 2248) and CRS (n = 620) with a median OS of 8.6, 10.9, 14.8 and 16.3 months, respectively (p < 0.001). Compared to patients who underwent no surgery, patients who underwent CRS were younger (58.9±13.4 vs. 62.0±13.1 years), had lower proportion of disease involving multiple sites (5.0% vs. 26.2%), and were more likely to have clinically occult disease (cM0 58.9% vs. 7.3%) - all p < 0.001. OS for propensity matched patients who underwent CRS (n = 490) was longer than NS (16.3 vs. 8.8 months, p < 0.001), including those with clinical M1 stage (n = 203) in both unmatched and propensity matched (median OS 19.7 vs. 8.6 months, p < 0.001) cohorts. On Cox regression model using the matched data, the hazard ratio for CRS vs. NS was 0.80 (95%CI 0.76-0.84). In the immortal matched cohort, the corresponding median OS was 16.7 vs. 9.7 months, p < 0.001. Conclusions: CRS in addition to systemic chemotherapy may be associated with an OS benefit in a selected group of patients with metastatic gastric adenocarcinoma. Suboptimal matching for tumor burden is our major limitation. In contrast to studies that focus on gastrectomy alone in the setting of MGA, this study highlights the role of CRS among patients receiving systemic chemotherapy.
Molecular characterization of a gastric cancer transmitted from an organ donor to four transplant recipients.
Authors: Atreya Chloe Evelyn , Park Meyeon , Grenert James P. , Behr Spencer , Gonzalez Amalia , Chou Jonathan , Maisel Samantha , Friedlander Terence W. , Freise Chris E. , Shoji Jun , Semrad Thomas John , Chin-Hong Peter , Collisson Eric A. , Van Ziffle Jessica 
Published: February 2020

414 Background: Donor-derived malignancy may occur even when not suspected based on donor or recipient factors, including age and time to cancer diagnosis. Early recognition of donor-derived malignancy has treatment implications. We describe the molecular characterization of a gastric cancer transmitted from an organ donor to heart, liver (LR), left kidney (LKR), and right kidney-pancreas (KPR) recipients. Methods: IRB approval for chart review was obtained; LR, LKR, and KPR also provided research consent for molecular profiling. Short Tandem Repeat (STR) genotyping was performed by polymerase chain reaction and gel electrophoresis. Tumor and germline DNA from patients and the organ donor were subjected to next generation sequencing (NGS) of 479 genes. Fluorescence in situ hybridization (FISH) was used to confirm MET amplification. Results: Donor origin was established by STR analysis, with the tumors showing high levels of donor alleles. Pathology revealed a poorly differentiated adenocarcinoma with signet ring features. Immunohistochemical staining and CA-19-9 elevation were most consistent with gastric or pancreas origin. Tumor sequencing was notable for somatic mutation of CDH1, MET amplification and wild-type KRAS genes. Tumors from LR and KPR were nearly identical based on pathogenic variants, allele frequency, and copy number variation. Insufficient tumor cellularity in all LKR specimens precluded NGS profiling, but clinical testing found that the cancer was mismatch repair proficient; ERBB2 equivocal; and PDL-1 positive. A circulating tumor DNA test did not uncover any genomic alterations; however, MET amplification was confirmed in this tumor using FISH probes. Conclusions: STR analysis and reporting should be standard immediately following diagnosis of cancer in an organ transplant recipient to ascertain donor derivation. Further molecular characterization, including NGS, may aid in defining primary tumor origin. Here, diagnosis with PDL1-positive gastric cancer enabled use of pembrolizumab. One patient remains alive and without evidence of cancer following prompt organ explant after cancer was reported in other recipients.