bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II, prospective, single-arm, single-institutional, open-label clinical trial on laparoscopic sentinel node navigation surgery in early gastric cancer.
Authors: Park Do Joong , Park Young Suk , Lee Hye Seung , Park Young Soo , Lee Kyoung Ho , Kim Young Hoon , Park Kyoung Un , Ahn Sang-Hoon , Kim Hyung-Ho 
Published: March 2017

90 Background: The aim of this study was to evaluate the feasibility and safety of laparoscopic limited gastrectomy with sentinel basin (SB) dissection for gastric cancer using simultaneous indocyanine green and 99mTc-antimony sulfur colloid injections. Methods: The primary end point was the 3-year relapse-free survival rate of the patients who underwent laparoscopic sentinel node navigation surgery (SNNS). Secondary end points included sentinel node (SN) detection rate, false negative rate of intraoperative pathologic examinations for metastatic SN detection, postoperative morbidity and mortality, quality of life (QOL), and overall survival. Results: From July 2010 to April 2013, 100 patients were enrolled to this study. The SBs were identified in all patients (100%) by dual method. The mean number of SN and non-SN was 6.07 ± 3.84 [range 0-17] and 4.60 ± 4.76 [range 0-25]. Eleven patients had SN metastasis and they were converted to conventional laparoscopic gastrectomy with radical lymphadenectomy. Among 89 patients with negative SNs, 3 patients were considered as false negative of intraoperative pathological examination (3.37%). There was no significant difference between SN negative (n = 89) and positive (n = 11) groups in estimated blood loss, postoperative hospital stays and complication rate. Overall, QOL scores are more likely to be better in SNNS group than in conventional laparoscopic distal gastrectomy group. After median follow-up periods of 47.5 months in all patients, 4 patients who underwent SNNS died, and 2 patients who underwent SNNS had recurrences of cancer. The 3-year relapse-free survival rate for all patients (n = 100) was 97.0 %. In the subgroup analysis, the 3-year relapse-free for the SN negative group was 96.6%, and 100% for the SN positive group (P = 0.374). The 3-year overall survival rate was 98.0% for all patients; 97.7% for the SN negative group and 100% for the SN positive group (P = 0.418). Conclusions: Laparoscopic SNNS was feasible and safe in early gastric cancer. Phase III randomized controlled trial on comparing laparoscopic SNNS and conventional laparoscopic gastrectomy will be needed based on the present study. Clinical trial information: NCT01441310.
Trastuzumab beyond first progression in cases of HER2-positive advanced gastric or gastro-esophageal junction cancer: Initial results from KSCC1105, a trastuzumab observational cohort study.
Authors: Makiyama Akitaka , Shimokawa Mototsugu , Kashiwada Tomomi , Takahashi Ikuo , Emi Yasunori , Kusumoto Tetsuya , Yamamoto Kazuharu , Ishikawa Hiroshi , Negoro Yuji , Oki Eiji , Saeki Hiroshi , Kakeji Yoshihiro , Baba Hideo , Maehara Yoshihiko 
Published: March 2017

93 Background: The concept of using trastuzumab (Tmab) beyond progression (TBP) is currently accepted in HER2-positive metastatic breast cancer. However, TBP has never been investigated in cases of HER2-positive advanced gastric or gastro-esophageal junction (G/GEJ) cancer. KSCC1105 is an observational cohort study designed to investigate the clinical outcomes associated with Tmab combined with chemotherapy including TBP strategy in part, as used in clinical practice, for the treatment of advanced G/GEJ cancer. Methods: Patients (pts) with advanced HER2-positive G/GEJ cancer receiving Tmab between March 2011 and January 2014 were enrolled. Data regarding the baseline characteristics before Tmab plus chemotherapy, pre-specified Tmab-related adverse events, and effectiveness were collected retrospectively. Treatment outcomes were estimated using Kaplan-Meier method and compared using log-rank test. Results: Of 181 enrolled pts, 179 were eligible for analysis and 123 received Tmab as first-line chemotherapy. Among the 123 pts, 85 were able to undergo second-line therapy with or without Tmab. We divided these 85 pts into those treated with Tmab (TBP group, n = 59; 69%) and those treated without Tmab (non-TBP group, n = 26; 31%) in the second-line chemotherapy. The baseline characteristics were similar between the two groups. The median OS was significantly longer in the TBP group (12.8 months; 95% CI 9.0–16.5 months) than in the non-TBP group (7.9 months; 95% CI 5.1–10.7 months) (hazard ratio = 0.50; 95% CI 0.29–0.84; p = 0.010). Infusion-related events were more frequent in the TBP group (20.3%) than in the non-TBP group (11.5%); however, no significant difference was observed. No cardiac event-related death was observed in either group. Conclusions: TBP may be associated with a better prognosis, without severe toxicity. A randomized controlled trial to assess TBP (T-ACT trial; WJOG7112G) is currently being undertaken by the West Japan Oncology Group.
Trastuzumab beyond progression in patients with HER2-positive advanced gastric adenocarcinoma: A multicenter AGEO study.
Authors: Palle Juliette , Tougeron David , Pozet Astrid , Soularue Emilie , Artru Pascal , Le Roy Florence , Dubreuil Olivier , Sarabi Matthieu , Williet Nicolas , Manfredi Sylvain , Martin-Babau Jerome , Rebischung Christine , Ben Abdelghani Meher , Evesque Ludovic , Dreanic Johann , Hautefeuille Vincent , Louvet Christophe , Lecomte Thierry , Taïeb Julien , Zaanan Aziz 
Published: March 2017

94 Background: Trastuzumab in combination with platinum-based chemotherapy is the standard first line regimen in HER2 positive advanced gastric cancer. However, there is no data concerning continuation of trastuzumab beyond first line progression. Methods: This retrospective multicenter study include all consecutive patients with HER2 + advanced gastric or gastro-esophageal junction (GEJ) adenocarcinoma who received after progression of trastuzumab plus platinum-based chemotherapy, a second line chemotherapy with irinotecan, taxane or platinum salt, with or without trastuzumab. The prognostic variables with P values ≤0.10 in univariate analysis were eligible for the Cox multivariable regression model. Results: From August 2007 to March 2015, 104 patients were included (median age, 60.8 years; male, 78.8%; PS 0-1, 71.2%) with advanced (metastatic : 99%) gastric (45.2%) or GEJ (54.8%) cancer. All patients had received first line treatment based on trastuzumab plus fluoropyrimidine and cisplatin (n=54; 51.9%) or oxaliplatin (n=50; 48.1%). As second line chemotherapy, 67 patients (64.4%) received FOLFIRI regimen, including 19 who have continued trastuzumab; 23 patients (22.1%) received a taxane regimen (paclitaxel or docetaxel), including 12 with trastuzumab; and 14 patients (13.5%) received a platinum-based chemotherapy (different from that used in first-line), including 8 with trastuzumab. When considering all regimens of second-line chemotherapy, continuation (n=39) versus discontinuation (n=65) of trastuzumab was significantly associated with an increase on PFS (4.4 vs 2.3 months; p=0.002) and OS (12.6 vs 6.1 months; p=0.001). In multivariate Cox model (including ECOG PS, tumor grade, number of metastatic site, and second-line treatment), continuation of trastuzumab was significantly associated with longer PFS (HR=0.56; 95%CI [0.35-0.89]; p=0.01) and OS (HR=0.47; 95%CI [0.28-0.79]; p=0.004). Conclusions: This study suggests that maintenance of trastuzumab plus second line chemotherapy beyond disease progression has clinical benefit in patients with HER2 positive advanced gastric cancer. These results deserve a prospective randomized validation.
Phase II study of intraperitoneal paclitaxel plus S-1/paclitaxel for gastric cancer with positive peritoneal cytology: CY-PHOENIX trial.
Authors: Aizawa Masaki , Ishigami Hironori , Yabusaki Hiroshi , Nashimoto Atsushi , Imamoto Haruhiko , Imano Motohiro , Yamashita Hiroharu , Kishi Kentaro , Kodera Yasuhiro , Uenosono Yoshikazu , Fujiwara Yoshiyuki , Hidemura Akio , Tamura Shigeyuki , Fukushima Ryoji , Yamaguchi Hironori , Kitayama Joji ,   Japan Intraperitoneal Chemotherapy Study Group (JIPG)
Published: March 2017

96 Background: The presence of free cancer cells in the peritoneal cavity has been known as a poor prognostic factor in gastric cancer patients. Intraperitoneal (IP) paclitaxel (PTX) provides powerful local effects in the peritoneal cavity, and we previously reported the efficacy and safety of a regimen combining IP PTX with S-1/PTX in gastric cancer patients with peritoneal metastasis. This multicenter phase II study was conducted to evaluate the efficacy of IP PTX plus S-1/PTX for gastric cancer with positive peritoneal cytology. Methods: Eligibility criteria included pathologically confirmed gastric adenocarcinoma, intraperitoneal free cancer cells confirmed by peritoneal washing cytology, and no evidence of overt distant metastasis including macroscopic peritoneal metastasis. Patients were administered IP PTX 20 mg/m2, intravenous PTX 50 mg/m2 on days 1 and 8, and S-1 80 mg/m2/day on days 1-14, q3 weeks. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Thirty eight patients were enrolled and fully evaluated for OS and toxicity. The median number of courses was 12.5 (range 2-35). The 1-year OS rate was 84.2% (95 % confidence interval, 68.2-92.6%). Of 3 patients with target lesions, partial response and stable disease were obtained in 2 and 1 patient(s), respectively. The peritoneal cytology findings converted from positive to negative in 36 (94.7 %) patients. The incidences of grade 3/4 hematological and non-hematological toxicities were 45 % and 26 %, respectively. The frequent grade 3/4 toxicities included neutropenia (23%), leukopenia (7%) and anemia (8%). Regarding adverse events related to IP port, 2 patients developed swelling around the port site. Conclusions: IP PTX with S-1/PTX was suggested to be a promising option for gastric cancer with positive peritoneal cytology through the clearance of cancer cells in the peritoneal cavity. Clinical trial information: UMIN000002850.
Adjuvant chemotherapy and overall survival in patients with node positive esophageal adenocarcinoma treated with neoadjuvant therapy and esophagectomy: A retrospective analysis using the National Cancer Database.
Authors: Ajmani Gaurav , Hensing Thomas A. , Kim Ki-Wan , Krantz Seth B. , Prinz Richard A , Talamonti Mark S. , Baker Marshall , Bentrem David J. , Roggin Kevin K. , Marsh Robert de Wilton 
Published: March 2017

97 Background: Node positive disease (N+) is frequent (~40%) following neoadjuvant therapy (NAT) and esophagectomy, yet limited data exist regarding the efficacy of adjuvant chemotherapy (AC) in this setting. There are no randomized studies addressing this question and single-institution, retrospective studies have reported mixed findings. Methods: A retrospective analysis was conducted using the National Cancer Database. 2,258 N+ patients were identified who had received NAT (83.3% chemoradiation and 17.7% chemotherapy alone) followed by esophagectomy. Patients with either incomplete staging or treatment data were excluded, as were those who died within 90 days following esophagectomy. Multivariate logistic regression was used to test for differences in patient characteristics between those who did (AC+) or did not (AC-) receive AC. Overall survival (OS) after surgery, by AC status, was analyzed using Cox regression in a sample propensity matched on relevant demographic and clinical factors. Results: 433/2258 patients received AC (19.2%). Patients who received AC tended to be younger (OR 0.98 per 1-year increase, P = .03) and had a higher socioeconomic status (SES) (OR 1.47 for high vs. low SES, P = .01). Although there were no significant differences in comorbidity (P = .32), AC+ patients had significantly shorter hospital stays after surgery (OR 0.98 per 1-day increase, P = .03). Pathologic T classification was unrelated to the likelihood of receiving AC (P = .39), however patients with a higher pathologic N stage were more likely receive AC (OR 2.12 for pN3 vs. pN1, P < .001). Those receiving AC had demonstrably longer OS from the time of surgery than those who did not (HR 0.78, P = .004). Median OS for the entire cohort was 22.6 months, whereas the administration of AC was associated with an improvement in median OS of 6.2 months (26.3 vs. 20.1 months). Conclusions: This retrospective analysis indicates that AC is associated with a significant improvement in OS (median 6.2 months) in N+ patients following NAT and esophagectomy. Further studies are needed to clarify the optimal role of AC in this setting.
A phase II study to examine the effectiveness of nutritional support with elemental diet for stage II/III gastric cancer patients receiving adjuvant chemotherapy with S-1 (OGSG 1108).
Authors: Kawada Junji , Imamura Hiroshi , Matsuyama Jin , Fukui Junichi , Nishikawa Kazuhiro , Kawase Tomono , Shimokawa Toshio , Kurokawa Yukinori , Satoh Taroh , Furukawa Hiroshi 
Published: March 2017

98 Background: Postoperative weight loss after gastrectomy causes deterioration in patient’s quality of life and tolerance for adjuvant chemotherapy in gastric cancer patients. Nutritional support may prevent postoperative weight loss and chemotherapy related adverse effects to improve compliance of adjuvant chemotherapy. Methods: Clinical stage II/III gastric cancer patients received R0 resection were registered in the first stage of the present study. Those patients were qualified and enrolled in the second stage who could intake more than 60% of elemental diet (Elental, 300 kcal/day for 14 days) in the postoperative period and were proven pathological stage II/III. Enrolled patients were planned to receive a total of 300 kcal/day of Elental for 24 weeks and additional courses was permitted up to 365 days. The primary endpoint was compliance of S-1: percent of patients who accomplish S-1 adjuvant for one year with more than 70% relative performance (RP). The secondary endpoints were nutritional parameters (body weight, BMI, s-albumin, s-protein, s-cholesterol), RP of 8 courses of S-1, adverse effects of S-1, RP of Elental and ratio of patients who were enrolled to the second stage. Results: From January 2012 to September 2014, 149 patients were registered in the first stage and 82 patients were enrolled in the second stage: including 50 men; 32 women; median age of 70 years (range, 42-85 years); and performance status were zero in 45 and one in 37 patients. Compliances of S-1 were 60.5% (95%CI: 49.0, 71.2) in 81 eligible patients and 69% (95%CI: 56.9, 79.5) in eligible patients without recurrence. In 81 eligible patients, RP of 8 courses of S-1 was 87.3 % (95%CI: 88.3, 85.9), and the body weight loss was 1.80kg (95%CI: -0.38, 4.48). Grade 3-4 toxicities were neutropenia 12%, anemia 4%, anorexia 4% and diarrhea 4%. Conclusions: Nutritional support for gastric cancer patients receiving adjuvant chemotherapy contributes to increase compliance of S-1 and potential effect on survival may be expected. Clinical trial information: UMIN000006872.
Checkmate 649: A randomized, multicenter, open-label, phase 3 study of nivolumab (Nivo) plus ipilimumab (Ipi) versus oxaliplatin plus fluoropyrimidine in patients (Pts) with previously untreated advanced or metastatic gastric (G) or gastroesophageal junction (GEJ) cancer.
Authors: Janjigian Yelena Yuriy , Adenis Antoine , Aucoin Jean-Sebastien , Barone Carlo , Boku Narikazu , Chau Ian , Cleary James M. , Feeney Kynan , Franke Fabio Andre , Moehler Markus , Roca Enrique Luis , Schenker Michael , Li Mingshun , Ajani Jaffer A. 
Published: March 2017

TPS213 Background: The combination ofoxaliplatin and fluoropyrimidine is a standard-of-care (SOC) first-line treatment of pts with metastatic G/GEJ cancer, resulting in a median overall survival (OS) of 8–11 months and objective response rate (ORR) of 30%–50%. This is accompanied by up to 77% grade 3/4 toxicities. Therefore, new treatment options are needed to improve survival and decrease toxicity in G/GEJ cancer. Nivo, a fully human IgG4 monoclonal antibody (mAb) that targets programmed death 1 (PD-1) and ipi, a fully human IgG1 mAb that targets cytotoxic T-lymphocyte–associated protein 4, have demonstrated manageable safety profiles and efficacy in multiple tumor types and may have a synergistic effect. In a phase 1/2 study in chemotherapy-refractory pts with G/GEJ/esophageal cancer with or without PD-1 ligand 1 (PD-L1) expression, second-line nivo 1 mg/kg + ipi 3 mg/kg demonstrated a manageable safety profile and resulted in 26% ORR (44% ORR in pts with PD-L1+ tumors), median OS of 6.9 months, and a 34% OS rate at 12 months (Janjigian Y, et al. J Clin Oncol. 2016;34[suppl][abstract 4010]). This open-label, phase 3 trial will evaluate nivo + ipi as first-line therapy for pts with G/GEJ cancer (CheckMate 649; NCT02872116). Methods: In this study, 870 pts aged ≥ 18 years with untreated advanced or metastatic G/GEJ cancer with or without PD-L1 expression will be randomized to receive nivo + ipi (4 doses; followed by nivo monotherapy) or investigator’s choice of capecitabine/oxaliplatin (XELOX) or fluorouracil/leucovorin/oxaliplatin (FOLFOX). Tumor tissue for determination of PD-L1 status must be provided from ≤ 6 months before study treatment. Pts receiving chemotherapy or radiotherapy for G/GEJ cancer within the last 6 months or pts with suspected autoimmune disease, uncontrolled medical disorder, or active infection are excluded. Primary endpoint is OS in pts with PD-L1+ tumors. Secondary endpoints include OS in all pts and progression-free survival and time to symptom deterioration in all pts and pts with PD-L1+ tumors. Clinical trial information: NCT02872116.
Use of circulating tumor DNA levels to gauge necessity of surgery for patients undergoing trimodality therapy for esophageal cancer.
Authors: Nabavizadeh Nima , McLaren Patrick James , Melendez Daira , Halsey Carol , Lopez Charles D. , D'Souza Sharlene , Enestvedt Brintha , Dolan James P. , Thomas Charles R. , Spellman Paul 
Published: March 2017

TPS214 Background: Up to 40% of patients receiving neoadjuvant esophageal chemoradiotherapy (CRT) are found to have no evidence of malignancy post-operatively. Given this, a sensitive and specific biomarker is needed, as reliable identification of complete responders may spare patients the morbidity and mortality of esophagectomies. Recent work with circulating tumor DNA (ctDNA) collected from the plasma of cancer patients indicates tumors routinely shed large amounts of DNA into the blood. This ctDNA can be systematically analyzed, quantification of which has been correlated with local and systemic disease burden. To further increase the specificity of analysis, the somatic mutations that arose in the tumor can be detected in ctDNA via targeted and whole genome sequencing. However, information on the feasibility of using ctDNA quantification as a biomarker for neoadjuvant response assessment is lacking. We hypothesize that quantification of ctDNA throughout trimodality therapy can be of practical use in the non-invasive monitoring of treatment response. The overall goal of this pilot project is to assess the feasibility and predictive utility of incorporating a sensitive, patient and tumor specific, plasma ctDNA quantification assay to more reliably identify complete responders following CRT. The long-term goal of this proposal is to apply these methods into prospective clinical trials for personalization of therapy by identifying neoadjuvant complete responders who may benefit from non-operative therapy. Methods: Pilot/feasibility study to evaluate the correlation between plasma ctDNA levels and pathologic treatment response. Plasma samples at different treatment time points (pre-CRT, during CRT, immediately pre-op and post-op) will be collected from 28 patients receiving pre-operative CRT followed by surgery for esophageal cancer. Patient-specific mutations will be identified through whole exome sequencing of paraffin-embedded pre-treatment biopsies. SafeSeqS PCR primers will be designed per patient for targeting of tumor mutations. Plasma-derived ctDNA will be assayed using the patient-specific SafeSeqS approach for each time point in triplicate.
Phase 1b dose-escalation and cohort-expansion study of the safety, tolerability, and efficacy of a novel transforming growth factor-β receptor I kinase inhibitor (galunisertib [G]) administered in combination with the anti-PD-L1 antibody (durvalumab [D]) in recurrent or refractory metastatic pancreatic cancer.
Authors: Melisi Davide , Guba Susan C. , Karasarides Maria , Andre Valerie 
Published: March 2017

TPS501 Background: Transforming growth factor-β (TGF-β) can suppress adaptive and innate anti-tumor immune responses. G (LY2157299) is an oral small molecule inhibitor of TGF-β receptor I kinase that down-regulates phosphorylation of SMAD2, abrogating activation of the canonical pathway. Programmed cell death-ligand 1 (PD-L1) is upregulated in a broad range of cancers including pancreatic; expression of PD-L1 helps tumors evade immune system detection through binding to PD-1 on cytotoxic T lymphocytes. D (MEDI4736) is an anti-PD-L1 monoclonal antibody that blocks PD-L1/PD-1 interactions. Blockade of both TGF-β and PD-L1 pathways could reverse immunosuppression associated with these molecules by activating adaptive and innate anti-tumor immune responses. Methods: This two part phase 1b open-label study will enroll patients (pts) with recurrent or refractory metastatic pancreatic cancer. Part 1 is a 3+3 dose-escalation assessment of the safety and tolerability of G (4 escalating doses) and D (constant dose). After dose-limiting toxicity evaluation, cohort expansion with approximately 25 pts at the dose determined in the dose escalation portion will occur. Eligible pts have recurrent or refractory metastatic pancreatic cancer ( ≤ 2 prior systemic regimens) regardless of PD-L1 status; ECOG PS 0-1. Pts who have received prior therapy targeting T-cell costimulation or checkpoint pathways, or have received a TGF-β R1 kinase inhibitor are not eligible. Pretreatment and on-treatment biopsies will be obtained. The primary objective is to assess safety and tolerability of G in combination with D by identifying dose-limiting toxicities and to assess safety of the combination at the dose-escalation-established dose. Secondary objectives are pharmacokinetics; immunogenicity; preliminary anti-tumor activity; overall survival. Exploratory objectives are to examine biomarkers relevant to G, D, and the disease state. Enrollment began on 15-June-2016; as of 13-Sep-2016, 1 pt entered treatment. Clinical trial information: NCT02734160.