bluuebunny/crossref_metadata_2025 huggingface dataset:
Disparities in place of death for patients with hematological malignancies, 1999 to 2015
Authors: Chino Fumiko , Kamal Arif H. , Chino Junzo , LeBlanc Thomas W.
Published: February 2019

Patients with hematologic malignancies (HMs) often receive aggressive end-of-life care and less frequently use hospice. Comprehensive longitudinal reporting on place of death, a key quality indicator, is lacking. Deidentified death certificate data were obtained via the National Center for Health Statistics for all HM deaths from 1999 to 2015. Multivariate regression analysis (MVA) was used to test for disparities in place of death associated with sociodemographic variables. During the study period, there were 951 435 HM deaths. Hospital deaths decreased from 54.6% in 1999 to 38.2% in 2015, whereas home (25.9% to 32.7%) and hospice facility deaths (0% to 12.1%) increased (all P < .001). On MVA of all cancers, HM patients had the lowest odds of home or hospice facility death (odds ratio [OR], 0.55; 95% confidence interval, 0.54-0.55). Older age (40-64 years: OR, 1.34; ≥65 years: OR, 1.89), being married (OR, 1.62), and having myeloma (OR, 1.34) were associated with home or hospice facility death, whereas being black or African American (OR, 0.68), Asian (OR, 0.58), or Hispanic (OR, 0.84) or having chronic leukemia (OR, 0.83) had decreased odds of dying at home or hospice (all P < .001). In conclusion, despite hospital deaths decreasing over time, patients with HMs remained more likely to die in the hospital than at home.
RETRACTED ARTICLE: Research on English translation distortion detection based on image evolution
Authors: Cui Lianhe
Published: January 2019

At present, there are serious distortions in the translation of image English characters. In order to alleviate this problem, this study improves the traditional algorithm, uses the Canny edge detection method as the edge detection method through experimental comparison and analysis, and combines the image evolution to analyze the English character translation of multiple complex images. Simultaneously, in this study, the closed space is used to fill the small holes in the target area, and some intrinsic characteristics of the text area are used to form the heuristic knowledge to limit the connected area, and the English candidate area is constructed for the image recognition algorithm of the image. Then, this study uses the English candidate area as the recognition area for translation recognition. The research shows that the algorithm has certain practical effects and can provide a theoretical reference for subsequent related research.
Changing nurses’ views of the therapeutic environment: randomised controlled trial
Authors: Csipke Emese , Wykes Til , Nash Stephen , Williams Paul , Koeser Leo , McCrone Paul , Rose Diana , Craig Tom
Published: January 2019

Background

Although patients value evidence-based therapeutic activities, little is known about nurses' perceptions.

Aims

To investigate whether implementing an activities training programme would positively alter staff perceptions of the ward or be detrimental through the increased workload (trial registration: ISRCTN 06545047).

Method

We conducted a stepped wedge cluster randomised trial involving 16 wards with psychology-led nurse training as the intervention. The main outcome was a staff self-report measure of perceptions of the ward (VOTE) and secondary outcomes measuring potential deterioration were the Index of Work Satisfaction (IWS) and the Maslach Burnout Inventory (MBI). Data were analysed using mixed-effects regression models, with repeated assessments from staff over time.

Results

There were 1075 valid outcome measurements from 539 nursing staff. VOTE scores did not change over time (standardised effect size 0.04, 95% CI –0.09 to 0.18, P = 0.54), neither did IWS or MBI scores (IWS, standardised effect size 0.02, 95% CI –0.11 to 0.16, P = 0.74; MBI standardised effect size –0.09, 95% CI –0.24 to 0.06, P = 0.24). There was a mean increase of 1.5 activities per ward (95% CI –0.4 to 3.4, P = 0.12) and on average 6.3 more patients attended groups (95% CI –4.1 to 16.6, P = 0.23) following training. Staff feedback on training was positive.

Conclusions

Our training programme did not change nurses' perceptions of the ward, job satisfaction or burnout. During the study period many service changes occurred, most having a negative impact through increased pressure on staffing, patient mix and management so it is perhaps unsurprising that we found no benefits or reduction in staff skill.

Declaration of interest

None.
Predictors of psychotic symptoms among young people with special educational needs
Authors: Stanfield Andrew C. , McKechanie Andrew G. , Lawrie Stephen M. , Johnstone Eve C. , Owens David G.C.
Published: January 2019

Background

Psychotic symptoms and psychotic disorders occur at increased rates in adults with intellectual disability, including borderline intellectual functioning, compared with the general population. Little is known about the development of such symptoms in this population.

Aims

To examine whether clinical factors predictive of psychotic disorder in a familial study of schizophrenia also apply to those with intellectual disability.

Method

Adolescents with special educational needs (SEN) were assessed with the Structured Interview for Schizotypy (SIS) and Childhood Behavioural Checklist (CBCL). These scores were used to prospectively divide participants based on their anticipated risk for psychotic disorder. A subsample were reassessed three times over 6 years, using the Positive and Negative Syndrome Scale (PANSS).

Results

The SEN group were more symptomatic than controls throughout (Cohen's d range for PANSS subscale scores: 0.54–1.4, all P < 0.007). Over 6 years of follow-up, those above the SIS and CBCL cut-off values at baseline were more likely than those below to display morbid positive psychotic symptoms (odds ratio, 3.5; 95% CI 1.3–9.0) and develop psychotic disorder (odds ratio, 11.4; 95% CI 2.6–50.1). Baseline SIS and CBCL cut-off values predicted psychotic disorder with sensitivity of 0.67, specificity of 0.85, positive predictive value of 0.26 and negative predictive value of 0.97.

Conclusions

Adolescents with SEN have increased psychotic and non-psychotic symptoms. The personality and behavioural features associated with later psychotic disorder in this group are similar to those in people with familial loading. Relatively simple screening measures may help identify those in this vulnerable group who do and do not require monitoring for psychotic symptoms.

Declaration of interest

None.
The potential drug cost impact of nivolumab (N) in patients with advanced/metastatic gastric cancer (GC) or gastroesophageal junction cancer (GEJC) in Canada.
Authors: Virik Kiran , Wilson Robert B
Published: January 2019

101

Background: Advanced/metastatic GC and GEJC is associated with poor survival outcomes. Systemic treatment options are limited in patients having had at least two lines of chemotherapy. Immune checkpoint inhibitors (ICIs) appear to be a promising therapeutic option in these patients. The role of predictive biomarkers to response to ICIs remains to be fully elucidated. This may ultimately inform the utility and thus potentially the drug cost incurred by ICIs. The ATTRACTION-2 phase III study using N in heavily pretreated advanced GC and GEJC patients improved outcomes. The use of ICIs has an anticipated budgetary impact on health care systems within the context of this potentially funded utilization of N. Methods: An estimation of the N drug cost alone for advanced de novo and relapsed cases diagnosed in 2017 and subsequently treated in the third line in Canada was undertaken. A cost estimate for N treatment in earlier lines was also evaluated. N cost per patient was calculated based on treatment indication, duration of treatment, standard dose/schedule. The analysis was performed in Canadian dollars ($) and assumed complete drug delivery and uncomplicated cycles. The cost of N was obtained from the pan Canadian Oncology Drug Review (PCODR) cost for N in lung cancer. The number of target patients and N utilization was derived from constructed schema to give a budget impact estimate. Results: Estimated N cost per treated patient is $15,770. The N drug cost in the third line setting is estimated at $5.9 million (M) for GC and $2.4M for GEJC, total $8.4M (IQR $3.9M-$18.7M). For first line and second line N in eligible pts respectively: potential drug cost is $23.7M, $11.8M for GC and $9.7M, $4.9M for GEJC. A sensitivity analysis was performed. Conclusions: ICIs potentially add a drug cost burden to the publically funded Canadian healthcare system. As biomarkers predictive of response evolve and patients are treated accordingly, the drug cost burden may lessen. Potential earlier line use and a longer duration of therapy will add to the estimated budgetary impact.
Survival impact of the response at twelve weeks in patients with advanced gastric cancer received first-line chemotherapy.
Authors: Arakaki Motoko , Aoki Masahiko , Imazeki Hiroshi , Shoji Hirokazu , Honma Yoshitaka , Iwasa Satoru , Okita Natsuko , Takashima Atsuo , Kato Ken , Boku Narikazu
Published: January 2019

103

Background: The continuation of first-line chemotherapy or the maintenance chemotherapy has been selected for advanced gastric cancer patients who have not progressed after 4 to 6 cycles of first-line chemotherapy. However, survival data about those patients remains unclear. We retrospectively assessed the impact of response at 12 weeks on survival for advanced gastric cancer who received first-line chemotherapy. Methods: Eligible patients had unresectable advanced gastric adenocarcinoma and treated for the combination chemotherapy with fluoropyrimidine and platinum from January 2010 to December 2017 in our hospital. Patients with HER2 positive were excluded. Patients were divided into three groups (PR, SD, or PD group) according to response at 12 weeks of first-line chemotherapy, and their overall survival and progression-free survival were assessed. Results: The total number of the subject was 249 whose median overall survival (mOS) and progression-free survival (mPFS) were 13.8 and 5.4 months. Among 152 patients with measurable lesions, 58, 42, and 52 patients achieved PR, SD, and PD at 12 weeks. mOS was 16.7 months in the PR group, 9.8 months in the SD group, and 5.7 months in the PD group. mPFS was 7.1 months in the PR group, 4.5 months in the SD group, and 1.7 months in the PD group. Among 97 patients without measurable lesions, 90 patients achieved nonCR/nonPD at 12 weeks of first-line chemotherapy whose mOS and mPFS were 17.9 months and 9.2 months while those were 9.6 months and 1.9 months in the remaining 7 patients with PD at 12 weeks. Conclusions: There were clear differences in survival among PR, SD, and PD at 12 weeks in patients with measurable lesions while patients without measurable lesions obtaining nonCR/nonPD at 12 weeks showed similar OS and PFS to those with measurable lesion obtaining PR in first-line chemotherapy for advanced gastric cancer. [Table: see text]
Anatomical topography of the tumor is related to prognostic survival in adenocarcinoma of esophagogastric junction?: Multivariable analysis.
Authors: Takeda Flavio Roberto , Sallum Rubens Antonio Aissar , Ribeiro Ulysses , de Castria Tiago Bianchi , Tustumi Francisco , Rocha Julio Rafael Mariano , Cecconello Ivan
Published: January 2019

108

Background: The adenocarcinoma of the esophagogastric junction (AJEG) is divided according to its anatomopathological classification (Siewert classification) for the choice of surgical treatment. However, both the Siewert classification and the location of the AJEG are related to different prognoses reported in the literature. Objectives: To compare the survival of patients with AJEG submitted to surgical treatment according to different topographies in the esophagogastric junction. Methods: 147 patients were selected between 2000 and 2016. One hundred and thirty (88%) males, mean age 64 years. Analyzing the retrieved lymph nodes, affected and the relation of resected and affected. AEGG (E: esophagus, E/TEG: gastric esophagus, TEG: gastric esophagus transition, TEG/G: esophageal gastric and stomach transition, and E/TEG/G: esophagus, transition and stomach) were analyzed for global survival, free of disease, and after relapse. Results: In relation to epidemiological data, the mean age was 63.1 years. Of the 147 patients 90 (61.2%) were submitted to neoadjuvant treatment. There was no statistical difference between the groups regarding histological grade, pT, pN, stage, tumor extension, lymphatic, venous and perineural invasion. The mean extension of the tumor was 5.4 cm. The mean number of retrieved lymphnodes were 32. Overall survival was E: 90%, E/TEG: 60%, TEG: 52%, TEG/G: 50% and E/TEG/G: 21%. (p <0.0001). Disease free of survival was E: 78%, E/TEG: 48%, TEG: 43%, TEG/G: 38% and E/TEG/G: 15%. (p <0.001). Conclusions: The survival of the AJEG varies according to the topography of the lesion, the tumors located closer to the stomach present worse survival than those located in the esophagus, except when the tumor is very extensive, from the esophagus to the stomach.
Subgroup analysis of JCOG0501 phase III study to confirm superiority of additional neoadjuvant chemotherapy with S-1 plus cisplatin to D2 gastrectomy with S-1 adjuvant chemotherapy for resectable type IV or large type III gastric cancer.
Authors: Katai Hitoshi , Iwasaki Yoshiaki , Terashima Masanori , Mizusawa Junki , Katayama Hiroshi , Nakamura Kenichi , Yoshikawa Takaki , Boku Narikazu , Yamada Takanobu , Fujiya Tsuneaki , Kawashima Yoshiyuki , Kinoshita Takahiro , Ohashi Manabu , Yamaue Hiroki , Sano Takeshi , Sasako Mitsuru ,   The Stomach Cancer Study Group of Japan Clinical Oncology Group
Published: January 2019

110

Background: We previously reported that the superiority of neoadjuvant chemotherapy (NAC) with S-1 plus cisplatin was not demonstrated for schirrhous or similar macroscopic type (type 4 or large type 3) gastric cancer. However, overall survival (OS) in both arms was better than previous reports (3-year OS: 62.4% in gastrectomy plus adjuvant S-1 [arm A] and 60.9% in NAC followed by gastrectomy plus adjuvant S-1 [arm B]). Therefore, we explored whether histology and peritoneal cytology are associated with treatment effect. Methods: After staging laparoscopy, a total of 300 eligible patients with clinically resectable disease were randomized to arm A, or arm B. In this report, treatment effect was explored in key subgroups such as histology and peritoneal cytology using the data from JCOG0501. Cox regression model was used to investigate the interaction between arms and subgroups. Results: Hazard ratio (HR) classified by histology (excluding one missing) was 0.686 (95% CI: 0.414-1.138) for non-signet type (n = 123) and 1.158 (95% CI: 0.805-1.666) for signet type (n = 176) (p = 0.098 for interaction). HR by peritoneal cytology was 0.870 (95%CI: 0.616-1.228) for the negative (n = 240) and 1.051 (95% CI: 0.598-1.845) for the positive (n = 60) (p = 0.513 for interaction). 3 year-OS of signet ring cell histology was 63.2% (95% CI: 52.2-72.4) in arm A and 51.7% (95% CI: 40.9-61.5) in arm B, that of non-signet ring cell histology was 62.3% (95% CI: 48.9-73.1) in arm A and 74.2% (95% CI: 61.4-83.3) in arm B, and that of peritoneal cytology positive was 35.7% (95% CI: 18.9-53.0) in arm A and 25.0% in arm B (95% CI: 11.8-40.7), and that of peritoneal cytology negative was 68.6% (95% CI: 59.5-76.1) in arm A and 70.6% (95% CI: 61.5-77.9) in arm B. Conclusions: NAC might be beneficial for non-signet ring cell histology. Considering the survival results, primary surgery followed by S-1 could be recommended for this disease even though histology was signet ring cell type or peritoneal cytology was positive. Clinical trial information: UMIN000000279.
Evaluation of intratumoral T cells in biopsies from advanced gastric cancer patients treated with andecaliximab and nivolumab.
Authors: Brachmann Carrie , Zhang Yafeng , Elboudwarej Emon , Turner Scott , Thai Dung , Bhargava Pankaj , Metges Jean-Philippe , Cunningham David , Catenacci Daniel V.T. , Van Cutsem Eric , Wainberg Zev A. , Shah Manish A.
Published: January 2019

118

Background: Preclinical studies suggest that MMP9 inhibition relieves immune suppression and promotes T cell infiltration to potentiate checkpoint blockade. To test this hypothesis, patient tumor samples obtained in a phase 2, open-label, randomized study (NCT02864381) of previously treated advanced gastric cancer comparing the MMP9-specific inhibitor andecaliximab (ADX) plus nivolumab (N) vs N alone were evaluated for T cell biomarkers. Methods: CD8 and PD-L1 (28-8 DAKO) were assessed by immunohistochemistry. IFNg, Teffector (Teff), and activated CD8+ T cell (ActT) gene signatures (GS) were assessed by RNASeq in archival baseline (BL) and biopsies obtained between weeks 5 and 9 (on-treatment; OT). Results: For both N and ADX/N, intratumoral CD8+ cells were significantly increased in OT biopsies relative to BL. The CD8+ OT increase was significantly greater for the ADX/N treatment relative to N in the PD-L1+ subgroup. In the ADX/N group only, IFNg, Teff, and ActT GS were significantly higher in OT biopsies relative to BL. OT change from BL of ≥ 300% vs <300% in CD8+ cells was associated with longer PFS (HR = 0.50, p = 0.032). The percentage of patients with increased CD8+ cells in OT biopsies was higher in the ADX/N arm. Conclusions: In the PD-L1+ ADX/N group, there was a significantly greater magnitude of CD8+ cell density increase, which was associated with gene signatures of T cell activation. More ADX/N-treated patients had an increase in tumor-associated CD8+ cells. Longer PFS was observed for patients in which CD8+ cells increased by ≥ 300%. These results are consistent with the hypothesis that ADX potentiates checkpoint inhibition by favorably altering the tumor immune microenvironment. Clinical trial information: NCT02864381. [Table: see text]
Comparison between S-1 monotherapy and S-1 plus cisplatin as postoperative chemotherapy after R0 resection for stage IV gastric cancer patients with oligometastasis: A multicenter retrospective study.
Authors: Kumagai Koshi , Yamaguchi Toshifumi , Takashima Atsuo , Nagashima Kengo , Kano Yosuke , Terashima Masanori , Yabusaki Hiroshi , Nishikawa Kazuhiro , Tanabe Kazuaki , Yunome Gen , Kawachi Yasuyuki , Yamada Takanobu , Fukunaga Hiroki , Kinoshita Takahiro , Watanabe Masaya , Taniguchi Hiroki , Sakamoto Takeshi , Ishiyama Koshiro , Boku Narikazu
Published: January 2019

123

Background: Gastric cancer (GC) with liver metastasis (M1: HEP) and para-aortic lymph node metastasis (M1: LYM) is categorized as stage IV. Based on the retrospective reports, surgical resection is weakly recommended for oligo-metastasis (O-Meta), if resectable, in the Japanese GC Treatment Guidelines 2018. Whereas S-1 monotherapy as adjuvant chemotherapy after surgery for stage II/III GC and S-1 plus cisplatin (SP) as palliative chemotherapy for unresectable stage IV GC are standard treatments, there is no consensus about post-operative chemotherapy (Post-Cx) after R0 resection of stage IV GC with O-Meta. Methods: The criteria for this retrospective study were: 1) no prior treatment for GC, 2) R0 resection including O-Meta (HEP or LYM) at 20 institutions in the Stomach Cancer Group of the Japan Clinical Oncology Group between 2007 and 2012, 3) histological confirmation of adenocarcinoma for primary tumor and O-Meta (M1: HEP or LYM), 4) no other distant metastasis such as peritoneal metastasis. Results: A total of 110 patients were collected. Of the 94 eligible patients, 84 patients underwent gastrectomy followed by Post-Cx with S-1 (S-1 group: n = 55), SP (SP group: n = 22) or others (Others group: n = 7), and 10 patients did not receive post-Cx (non-Cx group). Median age for the S-1, SP, Others and non-Cx groups were 66, 60, 61, and 79 years old. Sites of oligo-metastasis (HEP/LYM) was 21/34, 9/13, 2/5, and 7/3 in the S-1, SP, Others and non-Cx groups. The 3- / 5-year overall and relapse free survival (OS and PFS) rates of all the patients were 45.6/31.4% and 24.5/21.3%, respectively. Median OS was 28.5 and 36.5 months in the S-1 and SP groups (HR 0.99; 95% CI 0.54-1.82, p = 0.986). In multivariate analysis, no Post-Cx, over 70 years old were identified as the independent poor prognostic factor for OS (p < 0.05). Conclusions: R0 resection followed by Post-Cx for GC patients with O-Meta showed favorable survival, while there seems no additional benefit of cisplatin to S-1 alone.
Neoadjuvant treatment in patients with locally advanced gastric cancer.
Authors: Gumus Mahmut , Kaya Serap , Eris S , Alan Ozkan , Telli Tuba Akin , Okten Ilker Nihat , Gunaydin Ulug Mutlu , Tuylu Tuba Basoglu , Ay Seval , Ozturk Turkan , Ercelep Ozlem , Aktas Bilge , Akgun Babacan Nalan , Dane Faysal , Yumuk Fulden Perran
Published: January 2019

127

Background: Although neoadjuvant treatment has been standart approach in gastric cancer with the positive results of randomized controlled studies in recent years, neoadjuvant treatment approach rates are far below the expectations in our country. We aimed to evaluate neoadjuvant treatment approaches and results of gastric cancer patients in this retrospective study. Methods: We evaluated characteristics and survival outcomes of 54 patients that were operated after neoadjuvant systemic treatment out of 1,143 gastric cancer patients recorded in our database. Results: The median follow-up was 12 months in this study. 38% of the patients was female and the median age was 61 (24-78). While 46 % of the tumors were located in gastro-esophagial junction and cardia, others were located distally. All of the patients treated with neoadjuvant treatment had positive lymph nodes. While lymphatic and perineural invasion were detected in 67% of the patients, vascular invasion was detected in 39 % of the patients after the operation. While 43 % of the patients had grade 3 tumors, others had grade 1-2 tumors. R0 resection was achieved in 91% of the patients and D2 dissection was done in 82% of the patients. FOLFOX/XELOX, DCF/DCX, EOX/ECF and FLOT were applied as neoadjuvant treatment regimes in 19%, 50%, 21% and 11% of the patients respectively. The median chemotherapy cycle number was 3 applied pre and postoperatively. The disease control rate (response or stable disease) was achieved in 75,9 % of the patients after the neoadjuvant chemotherapy. In 13 patients progressive disease was detected and these patients were not operated. We found the median disease free survival was 25 months and overall survival was 41 months in survival analysis. Three year DFS was 29 % and 3 year OS was 52 %. Conclusions: Neoadjuvant treatment approach is important both to facilitate operation procedure and to evaluate efficacy of systemic treatment. As the survival advantage was shown in a study last year, FLOT regime is expected to be used more commonly. The patients have to be evaluated and the treatment decisions should be made in a multidisiplinary tumor board including surgeon, radiologist, medical oncologist to provide optimal treatment benefit.
Endoscopic intratumoral injection of OBP-301 (telomelysin) with radiotherapy in esophageal cancer patients unfit for standard treatments.
Authors: Tanabe Shunsuke , Tazawa Hiroshi , Kanaya Nobuhiko , Noma Kazuhiro , Kagawa Shunsuke , Kuroda Shinji , Urata Yasuo , Shirakawa Yasuhiro , Fujiwara Toshiyoshi
Published: January 2019

130

Background: OBP-301 (telomelysin) is an attenuated type-5 adenovirus with oncolytic potency that contains the human telomerase reverse transcriptase (hTERT) promoter to regulate viral replication. OBP-301 causes selective replication and lysis of a variety of cancer cells, and also inhibits the repair of radiation-induced DNA double-strand breaks, leading to radiosensitization. We aimed to assess intratumoral injection of OBP-301 with radiotherapy in esophageal cancer patients unfit for standard treatments. Methods: An open-label, phase I dose-escalation study of OBP-301 with radiotherapy was conducted in 13 histologically confirmed esophageal cancer patients who deemed unfit to receive surgery or chemotherapy. Study treatment consisted of intratumoral OBP-301 injections on days 1, 18, and 32 of treatment. Radiation therapy was administered concurrently over 6 weeks, beginning on day 4, to a total of 60 Gy. Virus administration was performed by intratumoral needle injection of the primary tumor through a flexible endoscope. The primary and secondary end points were incidence of dose-limiting toxicities and objective response rate. Results: Of 13 patients, seven, three, and three patients were treated in the cohorts with 1010, 1011, and 1012 virus particles of OBP-301, respectively. The patients comprised 10 males and 3 females, with median age of 79.7 years (range, 53 to 92 years). Common grade 1 and 2 toxicities included fever, esophagitis, pneumonitis, anorexia, constipation, and gastroesophageal reflux. All patients developed a transient, self-limited lymphopenia. Eight patients had local complete response (CR); all of them exhibited pathologically no viable malignant cells in biopsy specimens, and three had partial response. The objective response rate was 84.6%. The clinical CR rate was 80.0% in stage I and 66.7% in stage II/III, respectively. Histopathologic examination in post-treatment specimens showed massive infiltration of CD8+ cells in three partially responded tumors. Conclusions: Multiple courses of endoscopic OBP-301 injection with radiotherapy were feasible and provided definite clinical benefits in patients with esophageal cancer. Clinical trial information: 000010158.
Prognostic value of nutritional status for esophageal cancer patients undergoing neoadjuvant therapy and resection.
Authors: Saeed Sabrina D , Fontaine Jacques , Pena Luis , Hoffe Sarah E. , Frakes Jessica , Metha Rutika , Gurd Erin , Pimiento Jose Mario
Published: January 2019

133

Background: Malnutrition, linked to decreased patient tolerance to chemotherapy and increased rates of therapy-related toxicity, negatively affects cancer prognosis. Esophageal carcinomas (EC) frequently present with dysphagia and significant weight loss which may be exacerbated by neoadjuvant chemoradiation, placing EC patients at an increased risk of malnutrition. We therefore aim to assess the prognostic value of pre-operative malnutrition for esophageal cancer patients undergoing neoadjuvant therapy (NAT). Methods: Query of our institution’s IRB approved database of 1113 EC patients (pts) identified 725 individuals who underwent NAT followed by resection from 1994-2018. Seventy-six pts were considered to be at higher nutritional risk during NAT, as indicated by significant weight loss and enteral feeding tube requirement (ETF+), while 644 did not receive pre-operative feeding tube placement (ETF–). Clinicopathologic characteristics, post-operative outcomes, and survival were compared between ETF+ and ETF– using various statistical methods. Results: Of the included pts, 83% were male with a median age of 64.5 (28-86) years. Between ETF+ (n = 76) and ETF– (n = 644), pt characteristics were balanced in terms of initial stage, age, histology and tumor location. A higher percentage of ETF+ pts had > 5% weight loss before NAT (32 vs. 6%; p < .01). ETF+ was associated with a significantly worse median survival (27 vs. 77 m; p < .01), but not with increased post-operative length of hospital stay (p = .69), complications (p = .20) or tumor recurrence (p = .89). Although completion of chemotherapy (p = .46) and radiation (p = .49) were comparable between ETF+ and ETF–, tumor response was worse in the ETF+ group (71 vs. 60% non-complete response; p = .02). Conclusions: Our results suggest that baseline malnutrition is a risk factor for poor survival and negatively impacts the efficacy of neoadjuvant therapy in EC patients. Poor response to NAT in malnourished patients may stem from impaired immune function. Future prospective studies should evaluate other parameters for nutritional assessment to further assess the impact of malnutrition on tumor regression and survival after NAT.
Phase 1b study of andecaliximab (GS-5745, ADX) as monotherapy and in combination with nivolumab (nivo) in Japanese subjects with gastric or GEJ adenocarcinoma.
Authors: Yamaguchi Kensei , Satoh Taroh , Muro Kei , Takashima Atsuo , Ichimura Takashi , Sakai Daisuke , Kadowaki Shigenori , Chin Keisho , Kudo Toshihiro , Mitani Seiichiro , Kitano Shigehisa , Bhargava Pankaj , Zavodovskaya Marianna , Liu JieJane , Fukui Masato , Boku Narikazu
Published: January 2019

137

Background: Matrix metalloproteinase 9 (MMP9) is a poor prognostic factor in gastric cancer. Preclinical studies suggest that MMP9 inhibition can relieve immune suppression, promote T cell infiltration, and potentiate benefits of checkpoint blockade. ADX is a monoclonal antibody that inhibits the enzymatic activity of MMP9. In this study, safety, PK, exploratory biomarkers, and preliminary efficacy of ADX alone and in combination with nivo were assessed. Methods: Up to 6 Japanese subjects were to be enrolled in Cohort 1 (monotherapy ADX 800 mg IV Q2W), followed by 10 subjects in Cohort 4 (nivo plus ADX). Treatment was continued until PD or unacceptable toxicity. Tumor biopsies were collected before treatment and at week 6. Results: As of August 2018, 8 and 10 subjects were dosed in Cohort 1 & 4, respectively. All subjects received prior chemotherapy (median: 2, range: 1-4). In Cohort 1, Grade 3 AEs included anemia (25%), fatigue, general physical health deterioration, anorexia, and hydronephrosis (each 13%). All were not related to ADX. No DLTs nor responses were observed in Cohort 1. PK of ADX in Japanese subjects was similar to PK previously obtained in a non-Japanese population. The median t1/2 was ~8.1 days after 800 mg dose. All circulating MMP9 was bound to ADX at 2 weeks after dosing in Cohort 1. In Cohort 4, ≥Grade 3 AEs were anemia (20%), DIC, fatigue, anorexia, hypoglycemia, cholangitis, AST increased, neutropenia, and cancer pain (each 10%). ORR was 40% (4/10) and median PFS & OS have not been reached. Cohort 4 biomarker data will be presented. Conclusions: Preliminary safety data demonstrate a manageable safety profile for ADX alone and in combination with nivo. The combination appears to be promising. Clinical trial information: NCT02862535.
Safety of laparoscopic total gastrectomy with splenectomy for upper third advanced gastric cancer.
Authors: Akimoto Eigo , Tokunaga Masanori , Sato Reo , Kaito Akio , Kinoshita Takahiro
Published: January 2019

139

Background: In patients with locally advanced gastric cancer, total gastrectomy with splenectomy (TGS) is sometimes indicated when a tumor directly infiltrates the spleen or obvious splenic hilar lymph node metastasis exists. However, this procedure is technically demanding and can cause potentially fatal postoperative pancreas-related complications. TGS has increasingly been performed laparoscopically, particularly in East Asia. However, the number of reports regarding laparoscopic TGS (LTGS) is limited, and thus the feasibility of LTGS remains unclear. Methods: The present study included 68 patients with upper-third advanced gastric cancer who underwent LTGS or conventional open TGS (OTGS) between 2012 and 2018. Clinicopathological characteristics and surgical outcomes were retrospectively reviewed and compared between the groups. Results: There were no significant differences in sex, age, tumor size, cN factor, or cStage. cT4 was less frequently included in the LTGS group (21.4 vs 79.6 %, P < 0.01). In the LTGS group, operating time was longer (332 vs 247 min, P < 0.01) and blood loss was less (38 vs 598 ml, P < 0.01). Incidence of Clavien-Dindo grade 3 or higher complication (0 vs 24.1 %, P = 0.05) and median postoperative hospital stay (9 vs 11 days, P = 0.03) were significantly difference between the groups. The median number of harvested No. 10 and No.11d lymph nodes was equivalent between the groups. Conclusions: LTGS can be a safe procedure provided an experienced surgical team performs the surgery. Oncological safety remains unclear, and needs to be confirmed in future trials.
Long-term outcome of preoperative docetaxel with cisplatin plus S-1 therapy for advanced gastric cancer with extensive nodal metastasis (JCOG1002).
Authors: Morita Shinji , Ito Seiji , Sano Takeshi , Takahari Daisuke , Katayama Hiroshi , Mizusawa Junki , Sasako Mitsuru , Tanaka Yoichi , Kinoshita Takahiro , Terashima Masanori , Nashimoto Atsushi , Yamaue Hiroki , Fukushima Norimasa , Yamada Makoto , Fujiwara Yoshiyuki , Kimura Yutaka , Ikeda Atsuki , Yoshimura Tsunehiro
Published: January 2019

141

Background: Neoadjuvant chemotherapy (NAC) with cisplatin plus S-1 (CS) followed by gastrectomy with D2 plus para-aortic lymph node (PAN) dissection is regarded as a standard treatment in Japan for advanced gastric cancer with bulky lymph node (BN) and/or PAN metastasis based on the results of JCOG0405. In JCOG1002, we added docetaxel to CS (DCS) to further improve the long-term outcome. However the primary endpoint, clinical response rate (RR), did not meet the expected level (Ito S, Gastric Cancer. 2017). Herein we report the long-term survival. Methods: Patients with BN and/or PAN metastasis received two or three cycles of DCS therapy (docetaxel at 40 mg/m2 and cisplatin at 60 mg/m2 on day 1, S-1 at 40 mg/m2 twice daily for 2 weeks, were administered every four weeks) followed by gastrectomy with D2 plus PAN dissection and postoperative S-1 for 1 year. Results: Between July 2011 and May 2013, 53 patients were enrolled. Clinically, 17.0% of patients had both PAN and BN metastasis, and remaining patients had either PAN (26.4%) or BN (56.6%) metastasis. The clinical response rate (RR) was 57.7 % as assessed by RECIST v1.0, and the R0 resection rate was 84.6%, which did not exceed those in JCOG0405 (64.7% and 82.3%, respectively). The pathological RR defined as residual tumor corresponding to less than one-third the size of the original tumor was 34.6% in 52 eligible patients, which was slightly higher than in JCOG0405 (28.6%). Among all eligible patients, 5-year overall survival was 54.9% (95% confidence interval 40.3–67.3%) at the date cut-off of May 2018. Among 44 eligible patients with R0 resection, 5-year progression-free survival was 47.7% (95% confidence interval 32.5–61.5%). These were similar to the results of JCOG0405 (52.8% and 50.0%). Twenty patients developed cancer recurrence. The most frequent site of recurrence was lymph nodes (50.0% of all recurrences). Conclusions: Adding docetaxel to CS in NAC for extensive lymph node metastasis did not improve not only short-term outcomes but also long-term survival. NAC with CS followed by D2 + PAN dissection and postoperative S-1 remains standard for patients with extensive nodal metastasis. Clinical trial information: UMIN000006069.
Prognostic and predictive factors after failure of two drug lines for metastatic gastric adenocarcinomas: A French retrospective study.
Authors: Boussac Benjamin , Evesque Ludovic , Gal Jocelyn , Schiappa Renaud , Doyen Jerome , Benizri Emmanuel , Saint Angelique , Cavaglione Gerard , Francois Eric
Published: January 2019

149

Background: There is no therapeutic consensus after failure of two drug lines for metastatic gastric adenocarcinoma. The theoretical benefit of a third-line chemotherapy has to be weighed with the potential toxicity it could generate. It is essential to have prognostic and predictive factors to better select the candidate patients for a 3rd line chemotherapy. Methods: The medical records of patients (pts) treated in our institute from 2008 to 2018 who received at least two chemotherapy lines have been retrospectively analyzed. The main objective was to look for prognostic factors after failure of two chemotherapy lines. The secondary objectives were to look for predictive factors of progression-free survival, global survival, and RECIST response in 3rd line. Results: Out of a total of 153 pts identified, 68 received at least 2 chemotherapy lines and were eligible for analysis (44%). A third line was initiated for 41 pts (27%). Overall survival from the date of failure of a 2nd line treatment was 4.4 months (95% CI: 3.2-6.2). The median of progression-free survival in 3rd line was 1.68 months (CI 95%: 1.5-3.5 months), 5% of the patients responded to the treatment. In multivariate analysis, a period of less than 12 months between the administration of the 1st line of chemotherapy and the failure of a 2nd line was associated with a Hazard Ratio (HR) for death of 2.7 (p < 0.001; 95% CI 1.44 – 5.1). Pts who did not receive a 3rd line and female patients had a HR for death of 3.7 (p < 0.001; CI 95%: 1,9–7.3), and 2.8 (p < 0.001; 95% CI: 1,3–5.8) respectively. For patients who started a 3rd line: a PS ≥ 2 increased the risk of progression by 4.05 (p < 0.001; 95% CI: 1.1–15.7). Conclusions: Nearly one-third of pts were able to receive a third line chemotherapy. However, the benefit of this chemotherapy is low given the RECIST response rate, and the short overall and progression-free survival medians. Our results suggest that the administration of a third-line chemotherapy should only be considered for pts with 12 months or older ongoing metastatic lesions and whose general health condition is unaltered.
The effect of IMRT on acute toxicity in patients with gastric cancer treated with preoperative chemoradiation.
Authors: Moningi Shalini , Ajani Jaffer A. , Badgwell Brian D. , Mansfield Paul F. , Blum Murphy Mariela A. , Ikoma Naruhiko , Ho Jennifer , Suh Yelin , Holliday Emma Brey , Herman Joseph M. , Minsky Bruce D. , Koay Eugene Jon , Koong Albert , Krishnan Sunil , Smith Grace L. , Taniguchi Cullen M. , Das Prajnan
Published: January 2019

153

Background: Two trials are currently investigating preoperative chemoradiation (CRT) for localized gastric adenocarcinoma. However, radiation therapy (RT) can be associated with relatively high rates of acute toxicity. Newer techniques, such as intensity modulated RT (IMRT), could reduce toxicity by reducing radiation dose to normal structures. Our goal was to compare rates of toxicity and toxicity-related events in patients treated with IMRT compared to 3D conformal RT (3DCRT). Methods: The records of 202 gastric cancer patients treated with preoperative intent RT at our institution from 1998-2018 were retrospectively reviewed. Demographic data, treatment details, acute and late toxicities (CTCAE 4.0 criteria), progression and survival data were recorded. Patients who had stage IV disease were excluded. Statistical analysis included descriptive statistics, Cox regression analysis, and Kaplan-Meier survival. Results: 54% were male and the median age was 63. 82 patients received 3DCRT and 120 patients received IMRT (median 45Gy, IQR, 45-45Gy in each group). 78% of patients in the 3DCRT group and 91% of patients in the IMRT group received neoadjuvant chemotherapy prior to RT. 99% of patients received concurrent chemotherapy. The rate of grade 3-4 acute toxicity was significantly lower in patients treated with IMRT compared to 3DCRT (53% vs. 73%, p = 0.004). The composite rate of toxicity-related events (hospitalization, feeding tube, IV rehydration, or RT break) was also significantly lower in patients treated with IMRT compared to 3DCRT (80% vs. 91%, p = 0.031). 72% of patients who received 3DCRT and 68% of patients who received IMRT underwent subsequent surgical resection. The 3-year OS rate was 58.1% for patients receiving IMRT and 60.2% for patients receiving 3DCRT (p = 0.649). The 3-year PFS rate was 47.5% for patients receiving IMRT and 52.7% for patients receiving 3DCRT (p = 0.486). Conclusions: Our study indicates a marked reduction in the rates of grade 3-4 acute toxicity and toxicity-associated events in patients treated with IMRT compared to 3DCRT. These findings suggest that IMRT should be considered as the radiation modality in patients treated with preoperative CRT for gastric cancer.
Characteristics of long-term survivors in stage III gastric cancer patients.
Authors: Jang Youjin , Mok Youngjae
Published: January 2019

163

Background: Stage III gastric cancer patients had poor prognosis. This study aims to evaluate prognostic factor of stage III gastric cancer. Methods: We retrospectively studied 126 patients who were treated for stage III gastric cancer from Jan. 2007 to Dec. 2010 at Korea University Hospital and performed complete follow up for five years. Long-term survivor was defined more than five years survivor after gastrectomy. Results: Long-term survivor was 70 patients (55.6%). Tumor size, lymph node involvement, lymphatic invasion, venous invasion and neural invasion had prognostic significance on univariate analysis. But location of tumor, gross type, depth of invasion, TNM stage, combine resection, complication, histologic differentiation, type of operation and adjuvant treatment had no prognostic significance. The most common recurrence pattern was peritoneal recurrence (57.4%) according to analysis of recurrence pattern. The disease free survival according recurrence pattern was peritoneal recurrence (21.3 months), hematogenous recurrence (32.1 months), distant lymph node recurrence (12.0 months) and locoregional (12 months). The disease specific survival according recurrence pattern was peritoneal recurrence (9.2 months), hematogenous recurrence (11.3 months), distant lymph node recurrence (16.2 months) and locoregional (26.9 months). Conclusions: Lymph node involvement were the most significant prognostic factors on stage III gastric cancer after curative resection. Therefore, postoperative surveillance and adjuvant therapy were very carefully selected in stage III gastric cancer patient with extensive lymph node metastasis.
Tumor regression grade in gastric cancer after preoperative therapy.
Authors: Ikoma Naruhiko , Estrella Jeannelyn , Das Prajnan , Minsky Bruce D. , Fournier Keith F. , Mansfield Paul F. , Blum Mariela A. , Ajani Jaffer A. , Badgwell Brian D.
Published: January 2019

168

Background: The AJCC 8th edition updated ypStage TNM grouping for patients with gastric cancer due to the increasing use of preoperative therapy. We previously reported that nodal status after preoperative therapy (ypN) was most predictive for overall survival (OS). We intended to investigate if tumor regression grade (TRG) of the primary tumor scored by pathologists is helpful to predict survival of gastric cancer patients treated with preoperative therapy. Methods: We reviewed an institutional database to identify patients with clinically non-metastatic gastric adenocarcinoma who underwent gastrectomy after preoperative chemo- or chemoradiation therapy. Pathology reports were reviewed, and TRG was classified into following categories: 0 (complete response), 1 (few clusters of viable tumor cells, £1-2%), 2 (significant response, viable cells £ 50%), 3 (minor or no treatment response, viable cells > 50%). Associations between TRG and clinicopathological factors were examined. Univariable and multivariable Cox regressions were performed to determine associations with OS. Results: We identified 356 patients who met study criteria, including 80 (23%) patients with GEJ tumors; 56% were white and 60% were male. Preoperative chemoradiation therapy was given to 268 (75%). Fifty-six (16%) had TRG 0, 57 (16%) had TRG 1, 128 (36%) had TRG 2, and 115 (32%) had TRG 3. There were no associations between TRG and pretreatment factors. TRG 2 or 3 was associated with advanced ypT and ypN categories (both p < 0.001), ypM1 (p = 0.004), and R1 resection (0.052). Of all patients, median OS was 6.6 y, and 5-year OS was 54.1%. TRG 3 was associated with worse OS than other groups ( p = 0.015), while there was no significant OS difference among TRG 0-2 groups ( p = 0.803) in univariate analyses. On multivariable analysis, TRG was not associated with OS after adjustment for ypN status. Conclusions: In patients with gastric cancer who underwent preoperative therapy, TRG 3 was associated with advanced ypStage and R1 resection. Patients with TRG 3 had worse OS, due to associated advanced ypStage, particularly ypN+ status. Further studies are warranted to identify better definitions of treatment response and to identify the optimal modality for obtaining ypN0 status.
Integrative molecular profiling and response to chemotherapy on the COMPASS trial.
Authors: O'Kane Grainne M. , Fischer Sandra , Denroche Rob , Jang Gun Ho , Zhang Amy , Dodd Anna , Grant Robert C , Grunwald Barbara , Masoomian Mehdi M , Moura Shari , Elimova Elena , Prince Rebecca M. , Zogopoulos George , Notta Faiyaz , Wilson Julie , Gallinger Steven , Knox Jennifer J.
Published: January 2019

188

Background: Predictive mutational and transcriptional features in advanced PDAC are needed for improved patient stratification and treatment selection. Methods: Patients (pts) on the COMPASS trial with advanced PDAC are prospectively recruited prior to first-line chemotherapy for WGS and RNAseq. Tumor tissue undergoes enrichment by laser capture microdissection with genomic analyses available within eight wks. Tumor responses and clinical outcomes in this maturing cohort were correlated with molecular characteristics. Results: 157 pts underwent a tumor biopsy between Dec 2015 and Jul 2018 with over 95% success in achieving results. 141 genomes have been reported in pts planned to receive chemotherapy; the median time from biopsy to report was 35.5 days. In the ITT population,118 pts are summarised for first-line response. The median age was 63 yrs (29-81), 55% were male, and 16% had locally advanced disease. 66 (56%) received modified FFX as first-line treatment. 25 (21%) tumors displayed the Moffitt basal-like RNA signature which associated with chemotherapy resistance, with tumor shrinkage mainly observed in the classical RNA subtype (p = 0.002). GATA6 expression (log10 scale) clearly separated Moffitt subgroups with classical tumors exhibiting high expression (p < 0.0001). GATA6 in situ hybridization strongly correlated with RNAseq, (r = 0.89, p < 0.001) with strong correlation also seen with GATA6 IHC. The median overall survival (OS) in the classical group was 8.5 mths vs. 6.6 mths in the basal-like group (HR 0.53, 95% CI 0.32-0.89 p = 0.015). In those treated with mFFX, median OS was 10.1mths in classical versus 6.6mths in the basal-like subtypes, (HR 0.32, 95% CI 0.16-0.63, p=0.001). 30% of pts had potentially actionable genetic alterations including BRAF variants (n = 4) and an NTRK3-EML4 fusion in KRAS WT tumors (8%). Signatures of homologous recombination deficiency (HRD) were found in seven pts; two additional pts with BRCA germline variants did not exhibit somatic HRD hallmarks. Conclusions: Subsets of pts with advanced PDAC have actionable variants including those with HRD signatures and patients with KRAS WT tumors. GATA6 is a putative predictive biomarker of transcriptomic subgroups which should be incorporated in clinical trials. Clinical trial information: NCT02750657.