bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic evaluation of trifluridine/tipiracil (TT) versus nivolumab (N) in patients with advanced/metastatic gastric cancer (GC) or gastro-esophageal junction cancer (GEJC) in Canada.
Authors: Virik Kiran , Wilson Robert B. 
Published: February 2020

376 Background: Systemic treatment options in pre-treated patients with advanced/metastatic GC and GEJC have historically been limited especially in the third line or more. Recent potential advances in the therapeutic landscape of this patient population include TT (TAGS study) and immune checkpoint inhibitors (ICI) such as N (ATTRACTION-2 study). There is an anticipated budgetary impact on healthcare systems within the context of these potentially funded options. An economic evaluation can be instrumental in choosing a regimen if survival and quality of life are felt to be comparable. Methods: A cost minimization analysis was performed in Canadian dollars ($) comparing TT and N respectively in advanced de novo and relapsed GC/GEJC cases diagnosed in 2017 and subsequently treated in the third line in Canada. Direct costs including drug acquisition costs, supportive medications, transfusions, laboratory tests, physician visits, pharmacy and nursing time (health resource utilization-HRU) costs were calculated utilizing Ontario data. Direct costs for treatable adverse events G3/4 > 5% were incorporated. The analysis assumed complete drug delivery and the number of target patients was derived from constructed schema. Results: Compared to TT, the use of N was associated with a higher direct cost by a difference of $2.63 million (M) in the third line for GC and GEJC in Canada, principally reflecting a greater drug acquisition cost.The direct costs ranged (IQR) from 3.65M - 10.62M for TT to 3.3M – 15.69 M for N. N also had a greater HRU cost at 2.7 times that of TT and this was 64% of the direct costs for N excluding drug cost versus 42% of the direct non drug costs for TT. Supportive care (GCSF and transfusions) were 34% of the direct cost for TT excluding drug cost. A sensitivity analysis was performed. Conclusions: N generated a higher direct cost both for drug acquisition cost and other direct costs especially in HRU. Despite the increased cost of supportive care for adverse events related to TT, the direct non drug costs were less for this option. The use of biomarkers predictive of response may reduce the potential cost burden of the use of ICIs.
Comparing five-weekly S-1 plus cisplatin with tri-weekly capecitabine plus cisplatin in patients with HER2-negative recurrent gastric cancer after S-1 adjuvant therapy or chemotherapy naïve advanced gastric cancer: A pooled analysis of HERBIS-2 (OGSG 1103) and HERBIS-4A (OGSG 1105) trials.
Authors: Matsuyama Jin , Kawakami Hisato , Fujitani Kazumasa , Akamaru Yusuke , Tamura Shigeyuki , Endo Shunji , Kimura Yutaka , Makari Youichi , Tamura Takao , Sugimoto Naotoshi , Sakai Daisuke , Tsujinaka Toshimasa , Goto Masahiro , Kurokawa Yukinori , Shimokawa Toshio , Satoh Taroh 
Published: February 2020

379 Background: HERBIS-2 trial was a phase II trial where S-1 plus cisplatin (SP) and capecitabine plus cisplatin (XP) were compared in recurrent HER2 negative gastric cancer (GC) patients with recurrence free interval (RFI) by S-1containing adjuvant of ≥ 6 months. We performed pooled analyses of HERBIS-2 and HERBIS-4A trial where SP and XP were compared in chemotherapy-naive HER2 negative gastric cancer (GC) patients as these trials being identical. Methods: Both HERBIS-2 and 4A trials, patients were randomly assigned to receive either SP (S-1 at 40–60 mg twice daily for 21 days plus cisplatin at 60 mg/ m2on day 8, every 5 weeks) or XP (capecitabine 1,000 mg/m2twice daily for 14 days plus cisplatin 80 mg/m2on day 1, every 3 weeks). Results: In HERBIS-2 which was s closed early due to poor accrual, SP ( N= 10) tended to confer a better overall survival (OS) compared with XP ( N= 9)[18.7 (95%CI, 2.8 – NR) months vs.13.4 (95% CI, 5.2 – 31.3) months; hazard ratio (HR), 0.443 (95% CI, 0.156 – 1.258); P= .117]. In pooled analyses with HERBIS-2 and 4A, SP ( N= 50) vs. XP ( N = 51) showed longer progression free survival (6.4 vs.5.1 months; HR, 0.666; P= .62), OS (14.8 vs. 10.6 months; HR, 0.695; P= .099), time to treatment failure (4.6 vs. 3.6 months; HR, 0.668; P= .045), and higher disease control rate (86.4% vs. 68.1%, P= .149). Subgroup analysis revealed that OS benefit in SP arm compared to XP arm was significantly larger if the patient having PS of 0 [HR, 0.554 (95% CI, 0.309 to 0.959; interaction P= .035], or the tumor arising from upper area of stomach [HR, 0.266 (95% CI, 0.070 to 0.731); interaction P= .013] or harboring differentiated type cancer [HR, 0.433 (95% CI, 0.228 to 0.822); interaction P= .011], respectively. Conclusions: Our data suggest the use of SP in the 1stline setting in HER2 negative advanced or recurrent GC with RFI by S-1 adjuvant of ≥ 6 months. Pooled analyses further suggest SP as the standard 1st line chemotherapy for HER2 negative AGC irrespective of S-1 adjuvant in Japan. Clinical trial information: UMIN000006755/UMIN000006105.
Cost-effectiveness analysis of pressurized intraperitoneal aerosol chemotherapy (PIPAC C/D) in patients with gastric cancer and peritoneal metastasis.
Authors: Javanbakht Mehdi , Yaghoubi Mohsen , Mashayekhi Atefeh , Horvath Philipp , Koenigsrainer Alfred , Reymond Marc A. 
Published: February 2020

387 Background: The efficacy of systemic chemotherapy is still highly unsatisfactory for patients with gastric cancer and peritoneal metastases (PM). The aim of this study was to assess the costs effectiveness of pressurized intraperitoneal aerosol chemotherapy with low-dose cisplatin and doxorubicin (PIPAC C/D) for advanced gastric cancer. Methods: We developed a state transition Markov Model to estimate the costs and effectiveness of the use of PIPAC C/D versus palliative chemotherapy. Intervention was assessed in two different levels including upfront therapy (PIPAC C/D plus XELOX chemotherapy versus first-line chemotherapy alone) and second line therapy (PIPAC C/D only versus second-line chemotherapy (ramucirumab monotherapy)). Data from multiple sources such as published literature and UK-based databases were used to inform the economic model. Deterministic and probabilistic sensitivity analyses were conducted to explore the impact of key parameter variation on the results. Results: For the upfront therapy the estimated total costs in the intervention and comparator arms were £33,587(SD: £2,394) and £17,477 (£927) respectively. PIPAC C/D plus XELOX led to an increase of 0.56 in QALYs. Estimated incremental cost per quality adjusted life years (QALYs) was £28,879. Result from probabilistic sensitivity analysis showed that PIPAC C/D plus XELOX is cost effective in more than 50% of Monte Carlo simulations at £30,000 threshold. For the second-line therapy, the total costs for PIPAC C/D was £15,985 (£1,391) and for the second-line palliative chemotherapy was £36,319 (£3,673). PIPAC C/D led to an increase of 0.21 in QALYs and £20,222 reduction in costs, meaning the intervention is dominant strategy in the second line therapy as it is less costly and more effective. Conclusions: The cost effectiveness results for the upfront therapy indicate that PIPAC C/D plus chemotherapy intervention is more costly and more effective and a cost effective intervention. PIPAC C/D only intervention has the potential to reduce costs and improve clinical outcomes for patients with advanced gastric cancer with peritoneal metastasis and therefore a dominant strategy.
Long-term survival in patients with peritoneal metastasized gastric cancer treated with cytoreductive surgery and HIPEC: A multi-institutional cohort from PSOGI.
Authors: Brandl Andreas , Yonemura Yutaka , Glehen Olivier , Sugarbaker Paul H. , Rau Beate 
Published: February 2020

390 Background: Peritoneal metastasis of gastric cancer is relatively common (17%) and is associated with poor survival. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is still controversially discussed, as it has proven an increase in median survival in selected patients, but only a small subgroup reached long-term survival. The aim of this study was to collect and analyze a worldwide cohort of patients treated with CRS and HIPEC with long-term survival in order to explore relevant patient characteristics. Methods: We conducted a questionnaire, which was distributed to all collaborators of the Peritoneal Surface Oncology Group International (PSOGI). Inclusion criteria were: histopathologic proven peritoneal metastasis of gastric cancer, treated with CRS and HIPEC, and overall survival > 5 years. Patient, tumor, and therapeutic details were collected and analyzed. Results: A total of 29 patients with a mean age of 52.5 years and a mean PCI of 3.2 were included. The overall median survival was 11.0 years (min 5.0; max 27.9). The predictors completeness of cytoreduction (CC-0) and low PCI (PCI < 6) were present in 23/29 patients. 13/29 patients developed at a median of 82.2 months tumor recurrence. Tumor recurrence was associated with inferior median overall survival compared to patients without tumor recurrence (8.8 years vs. not reached; p = 0.002). Conclusions: Long-term survival and even cure are possible in patients with peritoneal metastasis of gastric cancer treated with CRS and HIPEC. Completeness of cytoreduction (CC-0) and low PCI seemed to be crucial. Further studies are needed in order to improve existing selection criteria.
Prognostic factor of nivolumab for advanced gastric cancer patients with poor performance status patients.
Authors: Matsumoto Toshihiko , Okazaki Ukyo , Kurioka Yusuke , Kimura Shogo , Tsuzuki Takao , Takagi Shinjiro , Takatani Masahiro , Morishita Hirofumi 
Published: February 2020

391 Background: Nivolumab has changed the treatment of advanced gastric cancer (AGC). Nivolumab shows better outcome compared to best supportive care in AGC patients who received at least two prior regimen. Although there is not reliable date of poor performance status(PS) AGC patients who received nivolumab. We investigated efficacy and safety of nivolumab for AGC patients with poor PS. Methods: We retrospectively collected clinicopathologic data from patients with AGC who received nivolumab monotherapy in Himeji Red Cross Hospital from October 2017 to June 2019. Results: 49 AGC patients who received nivolumab were analyzed. 27 patients were PS 0 or 1(Good Group), and 22 patients were PS 2 or 3(Poor Group). Median progression free survival and overall survival was 61 days and 180 days in Good Group and 36 days and 85 days in Poor Group. Overall survival (OS) was significantly shorter in Poor group(180 days vs 85 days, p = 0.0255). Disease control rate was 23% in Good group and 9% in Poor group. 33% patients were experienced immune related adverse event (iRAE) in Good Group, and 18% in Poor Group. We investigated prognostic factor of OS in Poor Group such as Royal Marsden Hospital Score(RMH score), modified Glasgow prognostic score(mGPS), and Japan Clinical Oncology Group (JCOG) prognostic index. RMH score and JCOG prognostic index good or moderate group was significantly longer overall survival than poor group (93 days vs 35 days (p = 0.0214)). JCOG prognostic index was most correlated with OS among these tools. Conclusions: This study suggested that nivolumab has a modest effect and is feasible as third line or later line for AGC patients. JCOG prognostic index was suggested to be effective in predicting prognosis in AGC patients who received nivolumab.
Efficacy and safety of nivolumab and irinotecan as third-line chemotherapy for advanced gastric cancer: A multi-institutional retrospective study.
Authors: Kumanishi Ryosuke , Mitani Seiichiro , Kadowaki Shigenori , MATSUSHIMA TOMOHIRO , Takahashi Naoki , Ogata Takatsugu , Yasui Hisateru , Ogata Misato , Satake Hironaga , Narita Yukiya , Masuishi Toshiki , Bando Hideaki , Hara Hiroki , Muro Kei 
Published: February 2020

396 Background: Although nivolumab (NIVO) and irinotecan (IRI) are currently used as third- or later-line therapy for advanced gastric cancer (AGC), few direct comparisons between them have been available. The present study therefore aims to compare the efficacy and safety of NIVO with IRI and explore clinical factors that predict efficacy. Methods: Patients with AGC who underwent NIVO or IRI treatment between November 2016 and June 2018 at three institution were retrospectively examined, subsequently evaluating response rates (RR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). The main inclusion criteria were patients pretreated with fluoropyrimidines and taxanes, Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0–2, and no previous NIVO or IRI treatment. Results: A total of 71 and 61 patients received NIVO and IRI, respectively, with both groups having similar baseline characteristics, except for gender. Efficacies were as follows (NIVO/IRI): RR, 20%/6% (p = 0.17); median PFS, 1.6 months (m)/1.8 m (HR 0.93, p = 0.67); median OS, 6.4 m/6.4 m (HR 0.91, p = 0.61); 1-year survival rate, 24.9%/19.3% (p = 0.61), respectively. Interaction analysis found no significant interaction between drugs and various factors such as ECOG PS (p = 0.59) and neutrophile/lymphocyte ratio (p = 0.33) related to OS. Subsequent chemotherapy agents were administered to 32 patients (45%) in the NIVO group (17 patients out of them received IRI) and 36 patients (59%) in the IRI group (23 patients out of them received NIVO) (p = 0.12). NIVO tended to have lower grade 3 or more AEs than IRI, especially neutropenia (3% vs. 28%, respectively; p < 0.01) and febrile neutropenia (1% vs. 8%, respectively; p = 0.09), as well as neutropenia, nausea, diarrhea, constipation, fatigue, and anorexia of any grade. Five patients developed immune-related adverse events in the NIVO group: pneumonitis (n = 1) and rash (n = 4). Conclusions: Although no remarkable differences in efficacy were found between NIVO and IRI for AGC, NIVO had a better safety profile compared to IRI. This study found no clinical factors that predicted efficacy.
Efficacy of palliative liquid nitrogen spray cryotherapy in curbing progression of dysphagia in esophageal cancer.
Authors: Eluri Swathi , Kaul Vivek , Sharma Neil R. , Gordon Stuart R. , Kachaamy Toufic , Smallfield George , Samarasena Jason , Trindade Arvind , Kothari Shivangi , Weber Jeffrey , Chang Kenneth J. , Benias Petros , McKinley Matthew J. , Shaheen Nicholas 
Published: February 2020

400 Background: Progressive dysphagia in locally advanced esophageal cancer worsens quality of life (QOL). Endoscopic cryoablation may effectively palliate dysphagia. Aim: To study the effect of palliative cryoablation with trūFreeze Spray Cryotherapy (SCT) in patients with esophageal cancer. Methods: This is an interim analysis of a multi-center prospective study of esophageal cancer patients who are non-surgical candidates, not on active systemic therapy, without esophageal stents, or prior SCT. SCT is an endoscopic ablation modality using liquid nitrogen (LN2) delivered by catheter. SCT occurred at 6 week intervals or as indicated at a dose of 2x30 or 3x30 secs/treatment site. Dysphagia and esophageal symptoms were assessed at baseline and after treatment with a 5-point Dysphagia score and the EORTC-QLQ-OES18 (higher score = more symptoms). Results: 39 subjects (mean age 74.4 ±12.2; 87% men, Table) had 182 treatment sessions over a mean follow-up of 206.9 days, and received a median 3 SCT sessions with an average dose of 90 (3x30) secs/site. There was 1 procedure related SAE (2.6% of patients and 0.5% procedures). Mean follow-up dysphagia score was 1.6 ±0.8 and 90% had same or improved dysphagia score after SCT treatment, p<0.01. On average, treated patients maintained the same or improved levels of dysphagia for 117 days. Esophageal QOL was maintained with improvement in “eating problems” (24.4 before treatment to 18.2 after, p=0.01). Only 4 subjects needed an esophageal stent (n=2) or gastrostomy tube (n=2) for nutrition. Conclusions: SCT for palliation of esophageal cancer was effective in limiting progression of dysphagia, while maintaining esophageal QOL. Only 10% required either esophageal stenting or feeding tube at >6 month follow-up. Clinical trial information: NCT03243734. [Table: see text]
A hybrid of the prone and left lateral decubitus positions for thoracoscopic esophagectomy with extended LN dissection for esophageal squamous cell carcinoma.
Authors: Kawakubo Hirofumi , Mayanagi Shuhei , Matsuda Satoru , Kitagawa Yuko 
Published: February 2020

402 Background: We first performed thoracoscopic esophagectomy (TE) as a minimally invasive procedure with the left decubitus position in 1996. In 2009 we developed a hybrid of the prone and left lateral decubitus positions for TE with extended LN dissection (Extensive-TE). The patient is fixed with the semi-prone position and we can easily change patient positions from the left lateral decubitus position to the prone position using rotation system of the operation table. The upper mediastinal procedure including lymphadenectomy along the right and left recurrent laryngeal nerve (RLN) is performed with the patient in the left lateral decubitus position, while the middle and lower mediastinal procedures are performed with the patient in the prone position with artificial pneumothorax. Methods: ESCC patients who underwent Extensive-TE between January 2009 and December 2016, were retrospectively reviewed. The patients’ background, surgical outcomes, postoperative complications and recurrence-free survival (RFS) were studied. Results: Primary tumor was located in Cervical esophagus for 2 (1%), the upper-thoracic esophagus for 28 (15%), the mid-thoracic esophagus for 104 (54%) and the lower-thoracic esophagus for 57 (30%). Thenumber of patients classified with pre-treatment clinical stage of 1/2/3/4 was 94(49%)/42(22%)/46(24%)/9(5%), respectively. Eight patients were evaluated as having cM1 disease due to supraclavicular LN metastasis. The number of patients classified with postoperative pathological stage of 0/1/2/3/4 was 5(3%)/70(37%)/48(26%)/49(27%)/19(7%), respectively. The average total operation time was 542.1 and blood loss was 274.2. The incidence of postoperative pneumonia, anastomotic leakage, chylothorax, and recurrent nerve palsy was 17%, 14%, 2%, and 7% respectively. One patient died postoperatively within 90 days after surgery. Three years RFSwith clinical stage of 1/2/3+4 was 91.5%/54.8%/51.9%, respectively. Conclusions: The magnifying effect of thoracoscopy enables us to perform more precise surgery and preserve nerve and vessels. Extensive-TEwith a hybrid position is thought to be feasible and effective methods.
Safety and efficacy of durvalumab following multimodality therapy for locally advanced esophageal and GEJ adenocarcinoma: Two-year follow-up results from Big Ten Cancer Research Consortium study.
Authors: Mamdani Hirva , Schneider Bryan J. , Kasi Pashtoon Murtaza , Abushahin Laith I. , Birdas Thomas J. , Kesler Kenneth , Burney Heather , Perkins Susan , Jalal Shadia Ibrahim 
Published: February 2020

404 Background: Concurrent chemoradiation(CRT) followed by esophagectomy is a standard of care for locally advanced esophageal(LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients(pts) experience disease relapse within the 1st yr after treatment(tx) completion. No adjuvant tx has been shown to improve survival in these pts. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown radiation +/- chemotherapy upregulate PD-1/PD-L1 pathway. Methods: We conducted a phase II trial evaluating safety and efficacy of durvalumab(durva) in pts with LA-EAC and GEJ adenocarcinoma who have residual disease in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: 24 pts were enrolled from 4/2016-1/2018(median age: 60yrs (range, 43-70). 18 received carbo/paclitaxel and 6 received cis/5-FU concurrently with radiation. Staging at diagnosis: T2N0(n = 3, 12.5%), T2N2(n = 3, 12.5%),T3N0(n = 6, 25%), T3N1(n = 6, 25%), T3N2(n = 4, 17%), T3N3(n = 1, 4%), T3Nx(n = 1, 4%).19 pts(79%) had positive lymph nodes(LNs) at the time of surgery following CRT. 12 pts completed 1yr of tx, 12 came off tx because of relapse(6), AEs(5), and consent withdrawal(1). Most common AEs were fatigue(n = 8, 33.3%) and nausea(n = 6, 25%). 3pts (12.5%) developed grade 3 irAEs: pneumonitis(1), hepatitis(1), colitis(1). At median follow up of 21.9mo(range, 1.7-23.9mo), 11 pts have relapsed: 9 distant and 2 locoregional. Two of 3 pts with grade 3 irAEs are alive and disease free at 17 and 23 mo respectively. 1-yr RFS and OS were 79.2% and 95.5%, respectively. RFS at 26 mo was 20.6%. Overall mOS and mOS after relapse were 28.1mo(range, 22.9-28.1) and 11.1 mo(range, 0.1-11.3mo) respectively. The study was expanded to enroll 14 additional pts who are currently undergoing tx. Conclusions: Adjuvant durvalumab following trimodality therapy for LA-EAC and GEJ adenocarcinoma is safe with improvement in 1-yr RFS to 79.2% compared to historical rate of 50%. RFS was 20.6% at 26 months. Evaluation of predictive biomarkers of RFS with durva is underway. Clinical trial information: NCT02639065.
Tumor treating fields (TTFields; 150 kHz) and FOLFOX combination treatment effects on gastric cancer in vitro.
Authors: Zeevi Einav , Gotlib Karnit , Schneiderman Rosa S , Munster Mijal , Porat Yaara , Voloshin Tali , Davidi Shiri , Shteingauz Anna , Kaynan Noa , Giladi Moshe , Kirson Eilon D. , Weinberg Uri , Kinzel Adrian , Palti Yoram 
Published: February 2020

406 Background: Gastric cancer is the third most common cause of cancer mortality worldwide, yet long-term survival in gastric cancer remains poor despite systemic therapeutic advances. FOLFOX (oxaliplatin, fluorouracil [5-FU], and leucovorin) is an approved chemotherapy regimen for gastric cancer treatment. Tumor Treating Fields (TTFields) are an antimitotic, loco-regional anticancer treatment delivered via non-invasive application of low intensity (1-3V/cm), intermediate frequency (100-500 kHz), alternating electrical fields. TTFields targets rapidly dividing cancer cells by disrupting microtubules leading to mitotic catastrophe, abnormal chromosome segregation, and apoptosis induction. We investigated the potential use of TTFields alone and in combination with FOLFOX for gastric carcinomas. Methods: Gastric cells (AGS and KATO III) were treated for 72 hours with TTFields (1.1 and 1.7 V/cm, respectively) at frequencies of 100-400 kHz using the inovitro system. Efficacy of TTFields and FOLFOX and its individual components was tested by applying TTFields at the optimal frequency in combination with various drug concentrations. Cell counts, apoptosis induction, clonogenic potential, and overall effect were determined. Results: The optimal TTFields frequency that led to the greatest cell count reduction (AGS, 55%; KATO III, 52%) was 150 kHz. The clonogenic potential was reduced by > 70% in both cell lines. TTFields combined with each FOLFOX component (oxaliplatin, 5-FU, or leucovorin) led to a significant reduction in AGS and KATO III cell survival (2-way ANOVA, P < 0.001 for each cell line) versus each treatment alone. In AGS, TTFields plus FOLFOX combination treatment led to a further reduction in the overall effect (cytotoxic and clonogenic; 79%) versus TTFields alone (65%) and FOLFOX alone (34%). Similar results were observed in KATO III cells. Conclusions: These results suggest that TTFields (150 kHz; optimal frequency) are an effective gastric cancer treatment; and combining TTFields with FOLFOX may further enhance efficacy. There is a strong rational to continue exploring the use of TTFields in combination with standard of care for gastric cancer treatment in the clinical settings.