bluuebunny/crossref_metadata_2025_split huggingface dataset:
Actigraphy as an objective measure of performance status in patients with advanced cancer.
Authors: Pirl William F. , Fujisawa Daisuke , Stagl Jamie , Eusebio Justin , Traeger Lara , El-Jawahri Areej , Greer Joseph A. , Temel Jennifer S. 
Published: February 2017

62 Background: Treatment decisions are often based on performance status (PS), a subjective rating of patient functioning derived from observation and patient-report. Devices that monitor physical activity, such as wrist actigraphs, can accurately measure the percent of time a person is immobile while awake (awake immobile). Thus, actigraphy may have potential to better estimate true PS. We compared actigraphy to both Eastern Cooperative Oncology Group PS (ECOG PS) and patient-reported physical activity as predictors of survival in patients with stage IV non-small cell lung cancer (NSCLC). Methods: Participants (n = 41) were ambulatory patients with stage IV NSCLC receiving care at MGH. Participants wore a watch-sized accelerometer device (ACTIWATCH 2) for three consecutive 24-hour periods (72 hours) and completed a self-report questionnaire about physical activity, scored as METS (metabolic equivalents) per week. Patients’ oncologists rated their ECOG PS (0-5) at the end of the 72-hour actigraphy period. Relationships among ECOG PS, awake immobile, and METs per week were tested with Pearson correlations. A ROC curve for 6-month survival was used to determine a meaningful cut-off for awake immobile. Unadjusted Cox regression models tested associations with survival from assessment times. Results: Participants’ ECOG PS ratings were: 0 (22%), 1 (63%), 2 (12%), and 3 (2%). ECOG PS and awake immobile were correlated (r = .42, p < .01). METS per week was correlated only with ECOG PS (r = -.35, p = .03). At time of analysis, 15 patients had died with a minimum follow up of 9 months. Among all patients, survival was predicted by ECOG PS, HR = 3.77 (95% CI 1.70-8.35), p < .01; awake immobile as both as a continuous (percentage points) and categorical ( > 23%) variable, HR = 1.04 (95% CI 1.00-1.09), p = .05 and HR = 4.12 (95% CI 1.37-12.39), p = .01, respectively; but not METS per week. Among patients with good EGOC PS (0-1), only awake immobile ( > 23%) predicted survival, HR = 5.80 (95% CI 1.39-24.12), p = .02. Moreover, within the largest ECOG group (PS1), awake immobile ( > 23%) still predicted survival, HR = 5.53 (95% CI 1.18-25.94), p = .03. Conclusions: Actigraphy, an objective measure of patient activity, may have utility in determining patient PS.
Effect of conversations about values and goals on anxiety in patients.
Authors: Paladino Joanna , Bernacki Rachelle , Hutchings Mathilde , Lipsitz Stuart R. , Neville Bridget A. , Gawande Atul , Block Susan 
Published: February 2017

9 Background: Patients with serious illness routinely receive treatments that do not align with their goals. Earlier clinical conversations about patients’ values and priorities lead to more goal-concordant care and improved quality of life, but clinician concerns about harming patients and taking away hope are barriers to appropriately timed discussions. Methods: A cluster-randomized controlled trial with oncology patients at high risk of death, identified by the surprise question. The intervention included a structured, patient-centered discussion about values and priorities conducted by trained oncology clinicians using the Serious Illness Conversation Guide. Patient anxiety (GAD-7) was measured by survey at baseline and every 2 months; anxiety, patient acceptability, and patient-reported behavior change were measured by survey 1 week after the intervention and at a matching time point for controls. Results: 342 patients enrolled (median age 62y): 176 intervention; 166 control. 102 conversations were completed in the intervention group. The mean anxiety (GAD-7) score prior to the intervention in the intervention group was 3.75 and in the control group was 3.80 (p = 0.72). However, a week after the intervention conversation (on average, the conversation was 10.4 weeks from baseline, IQR 3-13 weeks), there were significant differences. At 11.4 weeks, the intervention anxiety mean was 2.87, and the control mean was 4.26 (p = 0.011). Reductions persisted for 2 months after the conversation. Among patients who had the serious illness conversation and completed the acceptability survey: 86% reported that the conversation was worthwhile; 66% reported positive behavior changes as a result of the discussion; more than 80% reported that their hopefulness, peacefulness, and sense of control over medical decisions increased or did not change. Conclusions: The Serious Illness conversation lowered patient anxiety; this reduction was sustained for at least 2 months after the conversation. Patients viewed the serious illness conversation as worthwhile and reported enacting concrete positive behavior changes as a result of the discussion. Clinical trial information: NCT01786811.
The prevalence of lymph node metastases in clinical T1N0 thoracic esophageal cancer from the results of JCOG0502.
Authors: Akutsu Yasunori , Kato Ken , Igaki Hiroyasu , Ito Yoshinori , Nozaki Isao , Daiko Hiroyuki , Yano Masahiko , Udagawa Harushi , Nakagawa Satoru , Takagi Masakazu , Okabe Hiroshi , Abe Tetsuya , Nakamura Tetsu , Hihara Jun , Toh Yasushi , Shibuya Yuichi , Mizusawa Junki , Katayama Hiroshi , Nakamura Kenichi , Kitagawa Yuko ,   Japan Esophageal Oncology Group of Japan Clinical Oncology Group (JCOG)
Published: February 2017

10 Background: Recently, a limited operation to avoid needless lymph node (LN) dissection in clinical T1bN0 esophageal cancer (EC) is considered. However, how LN dissection or radiation field should be decided for such cases has not yet been clarified. The information about prevalence of LN metastases (LNMs) would be valuable when the radiation field and extent of LN dissection are considered in the treatment of T1bN0 EC. Methods: JCOG0502 is a randomized controlled trial including a patient preference arm comparing surgery alone to definitive chemoradiotherapy in clinical T1bN0 EC. By using baseline clinical and pathological data of JCOG0502, diagnosis accuracy of LNM was evaluated by comparing clinical and pathologic findings. Then, the sites of pathologic LNMs were determined and the initial sites and the prevalence of LNM were estimated. Results: Between Dec 2006 and Feb 2013, 213 patients (pts) enrolled to the surgery arm in JCOG0502. Pts with multiple lesions or without esophagectomy were excluded and remaining 186 pts were analyzed. Of the 186 pts of clinical T1bN0, 137 pts were diagnosed as LNM negative (73.7%: accuracy of diagnosis), however, 49 pts (26.3%) had pathologic LNMs. Pathologic LNMs were seen at 106recR, 106recL (all in mediastinal region) in upper thoracic (Ut) EC, 101R, 101L, 104R, 104L (in the neck region), 106recR, 106recL, 106tbL, 105, 107, 108, 109L, 110 (in the mediastinal region), 1,2,3,7, 11 (in the abdominal region) in middle thoracic (Mt) EC, and 105, 106recL, 110 (in the mediastinal region), 1, 2, 3, 7 (in the abdominal region) in lower thoracic (Lt) EC, respectively. Of the 49 pts who had pathologic LNMs, 32 pts (65%) were of pathologically N2 or more. Furthermore, 18 pts (37%) had skip LNM (LNM of N2, N3 or N4 without N1). The solitary pathologic LNM was observed in 25 pts: N1 (106recR, 106recL) in Ut, N1 (106recR, 106recL, 108), N2 (101R, 105, 110, 1, 3, 7), in Mt, N1(110, 1), N2 (106recL, 3, 7) in Lt, respectively. Conclusions: In the current status of clinical diagnosis, limited LN dissection or limited field of radiation are not recommended. In surgery, D2 LN dissection is necessary and three-field LN dissection is recommended especially in middle thoracic EC even for clinical T1bN0. Clinical trial information: UMIN000000551.
Randomized controlled trial to evaluate splenectomy in total gastrectomy for proximal gastric carcinoma (JCOG0110): Final survival analysis.
Authors: Sano Takeshi , Sasako Mitsuru , Mizusawa Junki , Katayama Hiroshi , Katai Hitoshi , Yoshikawa Takaki , Yabusaki Hiroshi , Ito Seiji , Kaji Masahide , Imamura Hiroshi , Fukushima Norimasa , Fujitani Kazumasa , Iwasaki Yoshiaki , Kinoshita Taira 
Published: February 2017

103 Background: We conducted a RCT to compare splenectomy and spleen preservation in total gastrectomy and reported higher morbidity and larger blood loss in splenectomy at 2010 ASCO Annual Meeting. Survival analysis after 5-year follow-up is now complete. Methods: Proximal gastric adenocarcinoma of T2-4/N0-2/M0 not invading the greater curvature was eligible. During operation surgeons confirmed that R0 resection was possible with negative lavage cytology, and the patient was randomized into splenectomy or spleen-preserving arm. The primary endpoint was OS. The trial was designed to confirm non-inferiority of spleen preservation to splenectomy in OS with a non-inferiority margin of the hazard ratio (HR) as 1.21. The planned sample size was 500 pts with a power of 70% and a one-sided alpha of 5%. Results: Between June 2002 and March 2009, 505 patients (splenectomy 254, spleen-preservation 251) were enrolled from 36 institutions. The first 319 patients were treated without adjuvant therapy by protocol, but after the S-1 adjuvant effect was established in 2006, patients with pathological stage II and III tumors received adjuvant S-1 by amended protocol. The 5-year survivals were 75.1% and 76.4% in the splenectomy and spleen-preserving arms, respectively. The HR was 0.88 [90.7% CI 0.67-1.16] (<1.21); thus the non-inferiority of spleen preservation was confirmed (p=0.025). The 5-year RFS was 68.4% in splenectomy arm and 70.5% in spleen-preserving arm. The HR was 0.87 [95% CI 0.65-1.17]. Subset analyses showed slightly better survival of spleen preservation in patients having deeper tumors (T3/T4), lymph node metastases, tumors located mainly in the middle stomach, and in those enrolled in the first study period of no-adjuvant protocol. Conclusions: This is the largest RCT of splenectomy in gastric cancer, and demonstrated significant non-inferiority of spleen preservation for the first time. In total gastrectomy for proximal gastric cancer which does not invade the greater curvature, prophylactic splenectomy should be avoided not only for operative safety but also for survival benefit. Clinical trial information: NCT00112099.
A randomized phase II trial of capecitabine plus cisplatin (XP) versus S-1 plus cisplatin (SP) as a first-line treatment for advanced gastric cancer: XP ascertainment versus SP randomized PII trial (XParTS II).
Authors: Kobayashi Michiya , Tsuburaya Akira , Nishikawa Kazuhiro , Kawada Junji , Namikawa Tsutomu , Fukushima Ryoji , Kojima Hiroshi , Tanabe Kazuaki , Yamaguchi Kazuya , Yoshino Shigefumi , Takahashi Masazumi , Hirabayashi Naoki , Sato Seiji , Nemoto Hiroshi , Rino Yasushi , Yoshikawa Takaki , Nakajima Junta , Morita Satoshi , Sakamoto Junichi 
Published: February 2017

105 Background: Capecitabine plus cisplatin (XP) is a standard global regimen for first-line treatment of advanced gastric cancer, however its efficacy compared to S-1 plus cisplatin (SP), a standard treatment in Japan has not been reported. To evaluate the efficacy of XP treatment, we conducted a multicenter randomized phase II trial comparing XP with SP for patients with advanced gastric cancer (ClinicalTrials.gov Identifier NCT0140624). Methods: Patients with unresectable metastatic or recurrent gastric cancer, 20–74 years of age and HER2-negative, were assigned to receive either S-1 40 mg/m2 bid for 21 days plus cisplatin 60 mg/m2 (day 8) every 5-week cycle or capecitabine 1000 mg/m2 bid for 14 days plus cisplatin 80 mg/m2 (day 1) every 3-week cycle. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), time to treatment failure, overall response rate (ORR) and safety. Planned sample size was 100 (50 in each arm) according to PFS at 24-weeks. Immunohistochemical evaluation of biomarkers was also implemented. Results: From November 2011 to June 2013, 116 patients were randomized: median age, 65 years; 79 (68%) male; 63 intestinal and 53 diffuse cancer subtypes. In 109 eligible patients, 24-week %PFS was higher in both groups than the protocol-specified threshold of 40%. Median PFS for SP vs. XP was 25 weeks vs. 23 weeks (HR, 0.76; 95%CI, 0.5-1.16; p=0.203); OS was 58 weeks vs. 56 weeks (HR, 0.90; 95%CI, 0.52-1.57; p=0.712); and ORR was 27.5% vs. 32.7% (p=0.562), respectively. Sub-group analysis by histological classification showed that SP gave better PFS than XP in the diffuse type (HR, 0.42; 95%CI, 0.20-0.86; p=0.015) with no other statistical difference. Most common grade ≥3 adverse events with SP and XP were anemia (16%/ 19%), neutropenia (9%/17%), anorexia (18%/13%), diarrhea (11%/0%), nausea or vomiting (11%/15%), fatigue (5%/6%) and hyponatremia (7%/13%), respectively. Conclusions: XP and SP are comparable and can be recommended as 1st line treatments for advanced gastric cancer. Further analysis for biomarkers related to histology is warranted. Clinical trial information: NCT0140624.
Lapatinib versus lapatinib plus capecitabine as second-line treatment in HER-2-overexpressing metastatic gastro-esophageal cancer (GC): A randomized phase II trial of the Arbeitsgemeinschaft Internistische Onkologie (AIO).
Authors: Lorenzen Sylvie , Riera-Knorrenschild Jorge , Haag Georg Martin , Pohl Michael , Thuss-Patience Peter C. , Bassermann Florian , Helbig Ulrike , Weissinger Florian , Schnoy Elisabeth , Becker Klaus , Stocker Gertraud , Ruschoff Josef , Eisenmenger Andreas , Karapanagiotou-Schenkel Irini , Lordick Florian 
Published: February 2017

112 Background: HER2 amplification is present in a subgroup of gastroesophageal cancers (GCs). HER2 inhibition with trastuzumab has shown to improve outcomes in advanced disease. Lapatinib ditosylate (LAP), a dual anti-EGFR and anti-HER2 tyrosine kinase inhibitor with preclinical activity against GC, has been approved in HER2-positive breast cancer. We aimed to study the activity of LAP in HER2-amplified GC. Methods: Patients (pts) with HER2-positive (gene amplification or increased copy numbers based on predefined criteria) advanced GC were randomly allocated 1:1 to receive LAP 1250 mg per day 1-21 plus capecitabine (CAP) 2000mg/m² on days 1-14 of a 21-day cycle or LAP 1500 mg monotherapy day 1-21 after having failed on a platinum-based first-line therapy. HER2 status was assessed centrally. The primary endpoint was the objective response rate (ORR) as assessed by the investigator using RECIST 1.1 criteria. We aimed to include 38 pts per arm to show a response rate of >20% in either of the two arms. Results: 37 pts were enrolled (18 to LAP+CAP, 19 to LAP). Pts had received a median of three prior treatment lines, however, the treatment was intended to be tested as a second-line treatment. 12 pts in the LAP+CAP group (67%) and 12 pts in the LAP group (63%) had received prior trastuzumab. Only two pts (11.1%; 95% CI: 1.37 – 34.7), both in the LAP+CAP arm, achieved an objective response. The study was closed prematurely for futility. Median time to progression was 42 (95% CI: 38 to 61) days in the LAP group and 83 (95% CI: 42 to 86) days in the LAP+CAP group. Other secondary efficacy endpoints (progression-free and overall survival) were comparable in the two treatment groups. Rates of diarrhea were higher with LAP+CAP (61%; 95% CI: 35 to 83) compared to 26% (95%CI 9 to 51) with LAP mono, whereas other adverse events were mostly similar between the groups (18 [100%] vs. 17 [90%]). Conclusions: Lapatinib showed insufficient activity in HER2-amplified pretreated advanced GC. The safety profile of LAP or LAP+CAP was as expected with some more toxicity in the combination arm. Clinical trial information: NCT01145404.
Laparoscopic D2 subtotal gastrectomy versus conventional open surgery for advanced gastric cancer: The safety analysis from a multicenter prospective randomized controlled trial in China (CLASS-01 trial).
Authors: Hu Yanfeng , Huang Changming , Sun Yihong , Su Xiangqian , Li Ziyu , Xue Yingwei , Hu Jiankun , He Xianli , Tao Kaixiong , Zhao Gang , Suo Jian , Wei Hong-Bo , Hu Weiguo , Ying Mingang , Du Xiaohui , Li Guoxin ,   The Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) Group
Published: February 2017

122 Background: The efficacy of laparoscopic D2 gastrectomy for the treatment of advanced gastric cancer (AGC) with curative intent is still controversial. Thus, the Chinese Laparoscopic Gastrointestinal Surgery Study (CLASS) group conducted a multicenter prospective randomized controlled trial, aiming to evaluate the surgical safety and long-term outcomes of laparoscopic D2 gastrectomy compared with conventional open surgery for AGC. (NCT01609309) Methods: The patients with tumor located at distal stomach at clinical T2-4a, N0-3, M0 stage were eligible for enrollment, treated by either laparoscopic D2 distal subtotal gastrectomy (LG) or open D2 gastrectomy (OG) after randomization. Seventeen institutions currently participated in the study. The morbidity and mortality within postoperative 30 days were compared between the two groups. Results: A total of 607 consecutive eligible patients were randomly assigned to either LG group (n=308) or OG group (n=299) between September 2012 and January 2014. The compliance rates of D2 lymphadenectomy in the LG group and OG group were similar (97.4% vs. 98.3%; P=0.591). Open conversion rate was 4.5%. There was no significant differences between the LG group and OG group in the incidence of intraoperative complication (5.8% vs. 4.3%; P=0.402), postoperative morbidity (18.8% vs. 14.7%; P=0.175), and mortality (0.6% vs. 0; P=0.499). The severity grade pattern was also similar according to the Clavien-Dindo classification (P=0.372). Conclusions: Laparoscopic D2 distal subtotal gastrectomy for AGC could be safely performed by experienced surgeons. Thus, our multicenter prospective study on long-term outcomes can be ongoing. Clinical trial information: NCT01609309.
Novel chemotherapy combinations for metastatic gastric adenocarcinoma (mAGC): An updated meta-analysis.
Authors: Wagner Anna Dorothea , Moehler Markus , Grothe Wilfried , Haerting Johannes , Unverzagt Susanne 
Published: February 2017

125 Background: Despite the successful integration of targeted therapies, chemotherapy remains the mainstay of treatment for mAGC. Uncertainty remains regarding the choice of the regimen. Methods: We searched: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE until February 2014; proceedings from ECCO, ESMO, ASCO until June 2014 with Selection criteria: Randomised controlled trials on chemotherapy in mAGC. Objectives: To assess and compare the effects on overall survival of regimens containing: 1) irinotecan (I) vs non-I, 2) docetaxel (D) vs non-D, 3) capecitabine (C) vs 5-FU, 4) S-1 vs 5-FU, 5) oxaliplatin (O) vs the same regimen containing cisplatin. For 1) and 2), substitutive (other chemotherapy substituted by I or D) and additive comparisons (I or D added) were analyzed separately. Results: The meta-analyses of overall survival included: Comparison 1) a. Substitutive: 5 trials, 724 patients (pts), with a HR of 0.85 (95% CI 0.73-0.99), b. Additive: 3 trials, 500 pts, with a HR of 0.88 (95% CI 0.76-1.03), both in favor of the I-containing regimens. Comparison 2) In total, 6 trials, 1702 pts, with a HR of 0.89 (95% CI 0.80-0.99) in favor of patients treated with D. a. Substitutive: 3 trials, 479 pts, with a HR of 1.05 (95% CI 0.87-1.27) in favor of patients treated without D. b. Additive: 3 trials, 1223 pts, with a HR of 0.82 (95% CI 0.87-0.93), in favor of D-containing regimens. If only studies (2 trials, 588 pts) are considered, in which D is added to a platinum/5-FU doublet, the HR is 0.79 (95% CI 0.64-0.98) in favor of the D-containing regimen. Comparison 3) 2 trials, 401 pts, with a HR of 0.85 (95% CI 0.68-1.06) in favor of the C-containing-regimen. Comparison 4) 2 trials, 1497 pts, with a HR of 0.89 (95% CI 0.80-1.0) in favor of the S-1-containing regimen. Comparison 5) 1 trial, 220 pts, with a HR of 0.82 (0.47-1.45) in favor of the O-containing regimen. Conclusions: All different chemotherapy combinations including I, D, O or oral 5-FU prodrugs are valid treatment options for mAGC. Among the comparisons analyzed above, only D-containing combinations, in which D was added to a single-agent or two-drug (platinum/5-FU) combination show a significant advantage in overall survival as compared to regimens without D.
Association of extensive delayed overmethylation influenced by advanced atrophy with risk for gastric cancer.
Authors: Oh Jung Hwan , Jung Sung Hoon , Cheung DaeYoung , Rhyu Mun Gan , Hong Seung Jin 
Published: February 2017

13 Background: Helicobacter pylori (HP) infection facilitates overmethylation of CpG-island genes, which can be delayed by advanced mucosal atrophy. Delayed overmethylation results in unstable cell phenotypes responsible for gastric cancer. To delineate cancer risk period, the overmethylation period from HP infection to severe atrophy was traced in the gastric cancer and dysplasia. Methods: A pair of normal-appearing mucosal specimens was obtained from the antrum and body of 110 HP-positive and 95 HP-negative controls, 99 cancer patients, and 118 dysplasia patients. Gastric mucosal atrophy was assessed using the endoscopic atrophic border score. Eight CpG-island genes adjacent to Alu (CDH1, ARRDC4, PPARG, TRAPPC2L) and LTR retroelements (MMP2, CDKN2A, RUNX2, RUNX3) and the TFF3 gene lacking CpG island were chosen. The methylation-variable sites in gene-control regions were analyzed using radioisotope-labeling methylation-specific PCR. Results: The antrum-specific TFF3 gene on the antrum tended to be overmethylated earlier than Alu-type CpG-island genes on the body in the HP-positive controls with mild mucosal atrophy (mean age; 50 years vs. 52 years). In moderate atrophic cases, the antrum-site TFF3 overmethylation was delayed four years compared with the whole cases (58 years vs. 54 years) and the Alu-type overmethylation on the body was early detected (49 years). Gastric cancer patients with moderate atrophy induced a late overmethylation on both the antrum and body site (56 and 58 years) and increased LTR-type slow overmethylation (OD, 5.3; 95% CI, 2.0-14.1). Dysplasia patients (65 years) older than gastric cancer sustained an early Alu-type overmethylation on the body site. Conclusions: Moderate atrophy of the gastric mucosa can delay overmethylation of CpG-island genes, which leads to unstable cancer period and subsequent stable dysplasia period.