bluuebunny/crossref_metadata_2025_split huggingface dataset:
Should signet-ring cell histology alter the treatment approach for clinical stage I gastric cancer?
Authors: Turgeon Michael K. , Gamboa Adriana C. , Rupji Manali , Lee Rachel M. , Switchenko Jeffrey M. , Russell Maria C. , Cardona Kenneth , Kooby David A. , Staley Charles A. , Maithel Shishir K. , Shah Mihir M. 
Published: February 2020

321 Background: Upfront surgery is standard of care for stage I gastric cancer. Despite this, many clinicians administer preoperative therapy for clinical stage I disease with signet ring cell histology, given its aggressive biology. We aimed to assess the validity of this practice. Methods: The National Cancer Database (2004-2015) was reviewed for pts with non-metastatic signet ring cell gastric cancer who underwent treatment with surgery alone, perioperative chemotherapy, neoadjuvant therapy, or adjuvant therapy. Analysis was stratified by preoperative clinical stage and pathologic stage. Primary outcome was overall survival (OS). Results: Of 3000 pts, median age was 61 (IQR: 51-70). 34% were clinical stage I (n = 1018) of which 53% received surgery alone (n = 542), 5% perioperative chemotherapy (n = 47), 12% neoadjuvant therapy (n = 125), and 30% adjuvant therapy (n = 304). Median follow-up was 26 mos. For clinical stage I disease, surgery alone was associated with improved median OS (108 mos) when compared to perioperative chemotherapy (80 mos), neoadjuvant therapy (41 mos), or adjuvant therapy (73 mos, all p < 0.001). For pathologic stage I, surgery alone had equivalent survival to perioperative and adjuvant therapy (5-yr OS: 81 vs 82 vs 79%, p = 0.22). Concordance between clinical and pathologic stage I was 56%, specifically, 41% of clinical stage I pts were upstaged to pathologic stage II (44%) and stage III (56%). Adjuvant therapy for these pts was associated with improved median OS compared to pretreatment (perioperative chemotherapy / neoadjuvant therapy) for those upstaged to pathologic stage II (122 vs 37mos, p < 0.001) or stage III (40 vs 18mos, p < 0.001) disease. Conclusions: Our stage-stratified study demonstrates improved survival with upfront surgery for clinical stage I signet ring cell gastric cancer. Despite 41% of clinical stage I pts being upstaged to stage II or III on final pathology, adjuvant therapy offers a favorable rescue strategy, with improved outcomes compared to those treated preoperatively. Surgery alone also affords similar survival for pathologic stage I disease compared to multimodal therapy. This study challenges the intrinsic bias to over-treat stage I signet ring cell gastric cancer.
Efficacy and safety of nab-paclitaxel plus ramucirumab versus paclitaxel plus ramucirumab as second-line treatment for patients with advanced gastric cancer: A single institutional experience.
Authors: Okunaka Mashiro , Kotani Daisuke , Demachi Ken , Kawazoe Akihito , Yoshino Takayuki , Shitara Kohei 
Published: February 2020

322 Background: Nanoparticle albumin-bound (nab)- paclitaxel (PTX) was non-inferiority to solvent-based paclitaxel as second-line for advanced gastric cancer (AGC) with fewer infusion-related reactions and a trend toward improved overall survival (OS) in patients (pts) with peritoneal metastasis (PM) or ascites in ABSOLUTE trial (Shitara K et al. Lancet Gastroenterol Hepatol. 2017). Furthermore, safety and efficacies of nab-PTX plus ramucirumab (RAM) was reported in a phase II trial (Bando H, et al. EJC 2018), although no randomised trial with PTX plus RAM is reported so far. Methods: We retrospectively reviewed consecutive pts with AGC receiving nab-PTX plus RAM or PTX plus RAM as second-line chemotherapy from June 2015 to January 2019 at the National Cancer Center Hospital East. Adverse events were evaluated using Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Progression-free survival (PFS) was calculated using the Kaplan-Meier method, and the differences were evaluated using the log-rank test. Results: A total of 257 pts were included for analysis with 118 pts treated with nab-PTX plus RAM and 139 pts with PTX plus RAM. 151 pts (59%) had peritoneal metastasis and 76 pts (30%) were associated with moderate or massive amounts of ascites. Objective response rates were similar between two groups (nab-PTX plus RAM 34.1% vs. PTX plus RAM 28.0%, p = 0.36). There were no significant differences in PFS (median 3.9 vs. 3.9 months, log-rank p = 0.34; hazard ratio [HR] = 1.14). HR of PFS was 0.96 in pts with PM and 0.79 in pts with moderate or massive ascites. The major grade 3 or higher adverse events were neutropenia (nab-PTX plus RAM 55.1% vs. PTX plus RAM 55.4%), leucopenia (28.8 vs. 35.3%), thrombocytopenia (5.1 vs. 2.9%), and febrile neutropenia (5.1 vs 9.4%). Conclusions: Efficacy and safety of nab-PTX plus RAM were comparable to those of PTX plus RAM in pts with AGC in clinical practice. nab-PTX plus RAM is a treatment option as second-line treatment in pts with AGC.
Clinicopathological features and treatment outcomes of young patients with gastric and esophageal cancers.
Authors: Beck Lauren Amanda , Ma Lucy Xiaolu , Espin-Garcia Osvaldo , Suzuki Chihiro , Jiang Di Maria , Liu Geoffrey , Chen Eric Xueyu , Knox Jennifer J. , Wong Rebecca , Brar Savtaj Singh , Swallow Carol Jane , Yeung Jonathan , Darling Gail Elizabeth , Conner James , Elimova Elena , Jang Raymond Woo-Jun 
Published: February 2020

325 Background: Gastric and esophageal (GE) cancers most commonly occur in older adults in their 60’s. There are inconsistent reports about prognosis in adolescent and young adult (AYA) pts, and treatment patterns and outcomes in this population have not been well characterized. Methods: A retrospective analysis was performed for AYA (age < 40) pts with GE cancers who presented to Princess Margaret Cancer Centre from 2008 to 2016. The Kaplan-Meier method was used to analyze progression free (PFS) and overall survival (OS). Results: We identified 57 AYA GE cancer pts (30 gastric, 27 esophageal). Features at diagnosis included: median age 35, 51% female (70% in gastric, 30% in esophageal), 82% with performance status 0-1, 83% Charlson Comorbidity Index 0, 54% stage IV. For gastric pts, 53% had diffuse histology and 47% had signet ring adenocarcinoma. There was a negative family history of gastric or esophageal cancer in 77% of pts. Curative intent treatment was used in 23 pts, palliative in 34. In curative pts, 48% had neoadjuvant therapy, 52% had upfront surgery. Of pts who underwent surgery, 57% had T3 or T4a disease and 38% had N2 or N3 disease. Median OS in curative pts was 39.9 months (95% CI 19.7-69.9), with a 5-year OS rate of 37% (95% CI 20-67). Of the palliative pts, 91% had chemotherapy. First line chemotherapy was a triplet regimen in 80%, doublet in 13%. The median number of treatment cycles on first line chemotherapy was 6, with a median PFS of 7.4 months (95% CI 5.4-10.5). At progression, 14 pts had second line treatment, 3 pts had third line and only 1 pt was treated beyond third line. Median OS in palliative pts was 12.1 months (95% CI 8-21.3). Conclusions: Consistent with the literature, our gastric AYA pts had increased female predominance and diffuse histology. Many AYA pts had advanced disease at diagnosis, with over half of pts presenting with metastatic disease. In both the curative and palliative setting, AYA pts did not have better survival outcomes despite being young with few comorbidities, suggesting they may have more aggressive biology.
Senior resident versus fellow participation during complex cancer operations.
Authors: de Geus Susanna W. L. , Kasumova Gyulnara G , Eskander Mariam F. , Ng Sing Chau , McAneny David B. , Tseng Jennifer F. , Sachs Teviah E. 
Published: February 2020

330 Background: Teaching hospitals that train both general surgery residents and fellows in complex general surgical oncology have become more common. Despite ACGME dictums, attending surgeons may favor either residents or fellows assisting on operations of greater complexity, depending upon a variety of factors, including local surgical culture. This study investigates whether participation of a senior resident versus a fellow impacts outcomes of complex cancer surgery. Methods: Patients who underwent esophagectomy, or gastrectomy with assistance from either a senior resident (PGY-4 or 5) or a fellow (PGY-6 to 8) were identified from the American College of Surgeon’s National Surgical Quality Improvement Program (2007-2012). Analyses were performed separately for each operation. Propensity-scores were created for the odds of undergoing the operation assisted by a fellow. Patients were matched based on propensity score, and outcomes were compared after matching. Results: In total, 1,160 esophagectomies and 2,432 gastrectomies were identified. Senior resident participation was reported in 60.2% and 86.6%, respectively. Resident involvement was associated with non-white race (17.0% vs. 13.8%; p < 0.001), and lower rates of neoadjuvant chemotherapy (6.4% vs. 11.7%; p < 0.001). After matching, rates major complication rates were slightly higher for patients who underwent esophagectomies involving a resident compared to fellow (38.1% vs. 31.8%; p = 0.0447). However, major complications rates were similar for gastrectomy (21.2% vs. 22.1%; p = 0.775). In addition, operative time was shorter for gastrectomy (212 vs. 232 min; p = 0.009) involving a resident compared to a fellow, but comparable for patients who underwent esophagectomy (327 vs. 337 min; p = 0.310). Conclusions: The results of this study suggest that senior resident participation in complex cancer operations does not negatively impact operative time or outcomes, compared to involvement of a surgical oncology fellow. Although confounding by operative autonomy may exist, these findings indicate that senior residents should be given the same opportunities as fellows to participate in these potentially more challenging operations.
First-line chemotherapy versus chemoradiation for resectable distal esophageal adenocarcinoma.
Authors: de Geus Susanna W. L. , Hirji Sameer , Ng Sing Chau , Sachs Teviah E. , Tseng Jennifer F. 
Published: February 2020

331 Background: Multiple randomized controlled trials have shown that both neoadjuvant chemotherapy (CT) and chemoradiation (CRT) convey survival benefit as compared to upfront surgery in patients with esophageal adenocarcinoma. However, international practice remains variable. Therefore, the present study compares the outcomes of first-line CT to CRT for patients with adenocarcinoma arising from the distal esophagus. Methods: Patients with clinical stage T2-T3, N0-N+ esophageal adenocarcinoma originating from the distal esophagus who received first-line CT or CRT were identified from the National Cancer Data Base (2006-2014). Propensity-score were created for the odds of receiving CRT. Patients were matched 1:1 based on propensity score. Subset analysis was performed in patients who underwent esophagectomy. Pathological complete response was defined as ypT0N0M0. Results: In total, 709 and 8,877 patients who received first-line CT and CRT were identified, respectively. CT was associated with stage cT2 (27.2% vs. 23.3%; p = 0.017), and treatment at a high-volume center (27.2% vs. 20.2%; p < 0.001). After matching, resection rates were comparable for patients who received first-line CT and CRT (62.2% vs. 63.7%; p = 0.545). However, median overall survival was slightly lower for patients who receive CT compared to CRT (23.7 vs. 28.4 months; p = 0.044). Among patients who underwent esophagectomy, time to surgery (135 vs. 134 days; p = 0.689) and median overall survival (37.0 vs. 40.5 months; p = 0.630) was similar between matched cohorts. However, complete response (15.8% vs. 25.8%; p < 0.001) and negative margin (94.3% vs. 88.9%; p = 0.004) rates were significantly lower after CT compared to CRT. Conclusions: In patients with esophageal adenocarcinoma, first-line CRT results in significantly higher pathological complete response rates, negative resection margins rates, and improved survival. These findings suggest that first-line CRT is preferable over CT when tolerated in patients with esophageal adenocarcinoma.
Cryotherapy in addition to chemotherapy for palliation of inoperable esophageal cancer: A multicenter prospective study.
Authors: Kachaamy Toufic , Sharma Neil R. , Pannala Rahul , Weber Jeffrey , Gorsuch Kimberly , Young Yashika , Salas Christina , Zelt Christina M. , Werling Heather , Gupta Digant , Vashi Pankaj G. 
Published: February 2020

342 Background: Palliation of dysphagia (Dys) in patients with inoperable esophageal cancer (EC) can be challenging. The major goal of palliation therapy is to improve patient’s quality of life (QoL) and Dys and allow adequate caloric intake. The most commonly used palliative modalities for Dys are radiation therapy (RT) and esophageal stenting. However, RT is limited by total dose and adverse events (AE) in patients receiving systemic therapy (ST), and stenting suffers from a high rate of AE including reflux and chest pain. A relatively new modality of liquid nitrogen endoscopic spray cryotherapy (cryo) has been reported in retrospective studies to improve Dys in patients receiving systemic therapy. We prospectively evaluated Dys and QoL of patients with inoperable EC undergoing cryo in addition to ST for palliation. Methods: A prospective multicenter study of 24 adult inoperable EC patients undergoing cryo and ST for palliation at 4 specialized cancer centers from Sep 2017 to Aug 2019. QoL was assessed using a modified EORTC QLQ-OES18 questionnaire (score 18 to 72, with higher scores indicating worse QoL). Dys was measured using a 4-point Likert scale: 0, no Dys; 1, Dys to solids; 2, Dys to semi-solids; 3, Dys to liquids; 4, Dys to saliva. Paired t-test was used to evaluate change in QoL and Dys between pre- and post-cryo. Results: There were 19 males and 5 females (17 stage IV, 5 stage III, and 2 stage II at diagnosis). Among 24 patients, a total of 71 cryo were performed, with a mean of 2.9 treatments per patient. After a median follow-up of 2 months, the mean EORTC score improved significantly from 35.4 at baseline to 25.5 at last follow-up ( p < 0.001). Similarly, the Dys score improved significantly from 2.0 at baseline to 0.87 at last follow-up ( p < 0.001). Grade 3 or higher AE were seen in only one patient (4%) who had GI bleeding 2 weeks after cryo and was diagnosed with bleeding from severe reflux esophagitis related to gastric outlet obstruction. Conclusions: The analysis of this multicenter prospective study shows that cryo in addition to ST for palliation of EC is well tolerated with significant improvement in Dys and QoL.
Correlation of heart dose with lymphopenia in esophageal cancer patients treated with chemoradiation.
Authors: Post Amber , Bowen Stephen R. , Nguyen Bao-Ngoc , Logan William , Zeng Jing , Apisarnthanarax Smith 
Published: February 2020

346 Background: Lymphopenia has been associated with survival and disease progression in esophageal cancer patients treated with chemoradiation (cRT). We previously published on our posterior-only proton therapy approach that maximally spares the heart and lungs, but at the cost of increased dose to the bone marrow in the vertebral bodies (VBs). We assessed hematologic toxicity in proton (PT) and IMRT treated patients and studied dosimetric parameters associated with hematologic toxicity. Methods: 35 patients treated with PT and 46 patients treated with IMRT for esophageal cancer between 2011-2018 were analyzed. Most patients were treated concurrently with carboplatin/paclitaxel to a median dose of 50.4 Gy. Lymphocyte, neutrophil and total leukocyte values while under treatment were recorded and graded per the CTCAE v4.03 toxicity scale, and the neutrophil-to-lymphocyte ratio (NLR) was computed. Mean dose and volumes (cc) receiving 5-50 Gy were calculated for the heart and VBs. A receiver-operator characteristic analysis was performed for univariate correlation between incidence of grade ≥3 hematotoxicity and dose-volume parameters. Results: Median follow-up was 36.1 months for all patients and the overall survival at 3 years was 57.5%. The rates of grade 3 or 4 hematologic toxicity in the PT group were 37.1% (leukopenia), 22.9% (neutropenia), and 80.0% (lymphopenia) versus 41.3%, 15.2% and 87.2%, respectively, for IMRT patients. There was a significant correlation between grade 4 lymphopenia and the heart V5, V10 and V20, but no significant correlation between VB doses with any hematotoxicity. Median NLR values and heart dose were higher in the IMRT group (9.17 vs 3.86 with PT, p = 0.0048; 10.5 vs 23.5Gy, p< 0.0001, respectively). There was a correlation between survival and NLR with a hazard ratio of 1.025 (CI 1.006 - 1.044). Conclusions: Low doses to the heart mediate severe lymphopenia in esophageal cancer patients treated with cRT. These data confirm the safety of the posterior-only proton approach without concern for increased hematologic toxicity despite higher vertebral body doses compared to IMRT. They also suggest that the blood pool is more important as a source of severe lymphopenia.
Prognostic impact of immune-related adverse events with nivolumab in patients with advanced gastric cancer: A multicenter retrospective analysis.
Authors: Ohya Yuno , Ando Takayuki , Ueda Akira , Ogawa Kohei , Motoo Iori , Kajiura Shinya , Tsukada Kenichiro , Hara Takuo , Suzuki Nobuhiro , Nakada Naokatsu , Takatori Shunsuke , Horikawa Naoki , Fujii Tsutomu , Yasuda Ichiro 
Published: February 2020

347 Background: Nivolumab was established as one of the standard treatments for previously treated advanced gastric cancer (AGC). The aim of this study is to evaluate the frequency of immune-related adverse events (irAEs) with Nivolumab and its impact on treatment efficacy in clinical practice. Methods: We performed multicenter retrospective analysis, which included 90 patients with advanced gastric cancer who received Nivolumab treatment between October 2017 and September 2019. The frequency of irAEs and its treatment outcome were evaluated, and survival was compared during Nivolumab treatment. Results: The characteristics of 90 patients in this analysis were as follows: median age (range), 68 (36-85); male/female, 56/34; ECOG PS 0-1/≥2, 62/28; number of metastatic sites 1/≥2, 36/56; treatment line 3/≥4, 63/27. Median treatment cycle of nivolumab treatment was 3 (range 1-26). The overall response in 68 patients with target lesions was 6.3% (4/68), and the median PFS and OS was 1.5 and 4.3 months, respectively. IrAEs were observed in 8 patients (8.8%), including grade 4 pneumonitis, grade 2 or 3 adrenal insufficiency, and grade 2 hypothyroidism, encephalitis, and immune thrombocytopenia. Median time to onset of irAEs was 1.3 (range 0.6-10.5) months. Six were treated with systemic corticosteroid therapy, and all irAEs were relieved. The median PFS and OS were 4.7 months (95%CI, 1.2-9.3) and 12.2 months (95% CI, 3.2-not reached) in patient with irAEs, and 1.4 months (95%CI, 1.1-1.9) and 4.1 months (95%CI, 2.6-6.6) in those without, respectively. There was significant difference in the PFS (p=0.005) and OS (p=0.03). Conclusions: Nivolumab was effective and well tolerated even in clinical practice. Development of irAEs may be associated with better outcome of Nivolumab in patients with AGC.
Analysis of weight loss as a prognostic factor in patients (pts) with advanced gastric cancer from REGARD, RAINBOW and RAINFALL phase III studies.
Authors: Mansoor Wasat , Roeland Eric , Chaudhry Aafia , Wei Ran , Chatterjee Anindya , Knoderer Holly , Abada Paolo , Klempner Samuel J. 
Published: February 2020

348 Background: Maintaining weight (wt) and adequate nutrition during systemic treatment in advanced gastric cancer (G/GEJ) therapy remains a challenge. We investigated the impact of early wt-loss on survival in three phase 3 studies of ramucirumab (R); REGARD (RG), RAINBOW (RB), and RAINFALL (RF) in G/GEJ. Methods: ITT pts were categorized into 2 groups based on their body wt change from start to end of cycle 1 (C1; C = 28 days in RG, RB; C = 21 days in RF): wt-loss < 3% vs ≥3%. Univariate Cox PH models were performed in each individual study to evaluate the effects of body wt change from the start to end of C1 on OS. A pooled meta-analysis stratified by study and a sensitivity analysis of the subgroup of responders was also performed. Results: A total of 311 (RG: 212 in R+BSC; 99 in Placebo (PB)+BSC), 591 (RB: 306 in the R+Paclitaxel (P); 285 PB+P), and 562 (RF: 279 in R+Cape/Cis (CC); 283 in PB+CC) pts with body wt data during C1 were evaluated. The number of pts with wt-loss of ≥3% and < 3% are shown in Table. Pts with wt-loss < 3% during C1 experienced longer OS compared to those with wt-loss ≥3%, irrespective of treatment arms across studies (Table). In pooled treatment arms within each study, the HR for wt-loss group ( < 3% vs ≥3%) was 0.359 (95% CI = 0.254, 0.507), 0.632 (0.497, 0.804), 0.752 (0.608, 0.930) in RG, RB, RF, respectively. In the meta-analysis that combined the 3-studies, univariate Cox PH model stratified by study showed consistent effect of early wt-loss on OS regardless of treatment arm, HR ( < 3% vs ≥3%) = 0.632 (0.546, 0.732). Conclusions: Analysis from three phase 3 studies demonstrates early wt-loss ≥3% during C1 is an important negative prognostic factor for survival in gastric/GEJ cancer. Prospective studies of the relationship of weight preserving nutritional interventions on OS are warranted. Clinical trial information: NCT00917384, NCT01170663, NCT02314117. [Table: see text]
Predictors of outcome following local excision for T1 rectal adenocarcinoma: A contemporary analysis.
Authors: Jayakrishnan Thejus Thayyil , Abel Stephen , Reichstein Ari , Fortunato Richard , Nosik Stanislav , McCormick James , Finley Gene Grant , Monga Dulabh K. , Kirichenko Alexander V. , Wegner Rodney E. 
Published: February 2020

35 Background: Local excision (LE) alone is a standard treatment option for appropriately selected early stage rectal adenocarcinoma patients. Guidelines for this therapeutic approach are based upon retrospective single institution data, some of which dates back 30 years. We thus sought to use the National Cancer Database (NCDB) to examine outcomes in a large cohort of patients with early stage rectal adenocarcinoma treated with LE and to identify/confirm predictors of outcome. Methods: We queried the NCDB for patients with pT1N0M0 rectal adenocarcinoma treated with local excision alone. Baseline characteristics were tabulated and included lymphovascular invasion (LVI), perineural invasion (PNI), grade, and size all of which have been recorded in the NCDB since 2010. Multivariable Cox regression was used to identify predictors of overall survival. Kaplan Meier curves were generated to compare survival based upon significant factors found on multivariable analysis. Results: Using the above criteria, we identified 887 patients eligible for analysis across 2010-2014. The median age was 67 and 57% of patients were male. The median tumor size was 1.5 cm (IQ range: 0.9-2.5 cm). A minority of patients had grade 3 tumors (5%), LVI (8%), or PNI ( < 1%). Median follow up was 36 months (1-83). On multivariable Cox regression, predictors of worse survival included: size > 4 cm, age > 67, higher comorbidity score, and presence of LVI. On Kaplan Meier analysis, 5 year OS was 75% vs. 74% for patients without and with LVI, respectively (p = 0.0115). In terms of size, the 5 year OS was 74% vs. 51%for size < 4cm and size > 4cm (p = 0.0138). Conclusions: Our large contemporary series demonstrates excellent survival outcomes in patients with early stage rectal adenocarcinoma treated with LE alone. LVI remains a predictor of outcome, while grade and perineural invasion were not significant in this analysis. This finding is likely due to a small number of patients with those characteristics.