bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dosimetric analysis of distal esophageal adenocarcinoma patients treated by intensity-modulated proton therapy with small spot size.
Authors: Liu Chenbin , Sio Terence Tai Weng , Bhangoo Ronik S , Rule William G. , Ross Helen J. , Paripati Harshita , Jaroszewski Dawn E. , Beamer Staci , Fleischer David , Ramirez Francisco , Ding Xiaoning , Bues Martin , Ashman Jonathan Ben , Liu Wei 
Published: January 2019

159 Background: Intensity-modulated proton therapy (IMPT) with small spot size has the potential to reduce dose to normal tissues but also introduces new confounding factors such as setup uncertainty, range uncertainty, and interplay effects due to breathing motion. We investigated plan quality and robustness of IMPT with small spot size for distal esophageal adenocarcinoma (DEA). Methods: 19 patients with DEA treated by IMPT were retrospectively evaluated. Spot sizes ranged from 2 to 6mm, with spot spacing of 5mm. All plans were generated using a commercial treatment planning system. In-house-developed dose-evaluation software modeled time-dependent spot delivery to incorporate interplay effects. Dose-volume-histogram (DVH) indices were used to evaluate plan quality and robustness was evaluated using the DVH band method. Results: For plan quality, median values of clinical target volume D95% and D5%-D95% (normalized to the prescribed doses), total lung mean dose, heart mean dose, and cord Dmax were 1.014, 0.035, 3.82Gy[RBE], 7.73Gy[RBE], 39.16Gy[RBE], respectively. For plan robustness, median band widths of the aforementioned DVH indices were 0.018, 0.048, 0.60Gy[RBE], 4.17Gy[RBE], and 2.36Gy[RBE], respectively. For interplay effects, median values of the aforementioned DVH indices were 0.99, 0.061, 4.07Gy[RBE], 7.87Gy[RBE], and 39.66Gy[RBE], respectively. Seven patients underwent esophagectomy after neoadjuvant chemoradiation, and five, three, and one of them achieved downstaging, near complete response, and pathologic complete response, respectively; R0 resection was achieved in all cases. For all patients, acute side effects were mostly limited to grades 1-2 only. The only grade 3 adverse events were related to feeding tube placement (8 patients); there were no RT-induced pneumonitis or other lung-related toxicities. Conclusions: IMPT plans with small spot size for DEA have good target dose coverage, homogeneity and normal tissue protection. Treatment plans are also robust to uncertainties and interplay effects. Early clinical results demonstrate low acute toxicity and encouraging clinical and pathologic response.
Patient-level costs of treating metastatic gastric cancer by treatment strategy.
Authors: Jeong Yunni , Mahar Alyson L. , Zagorski Brandon , Coburn Natalie 
Published: January 2019

167 Background: Half of gastric cancer patients in North America present with metastatic disease. The appropriate management of these patients is complex and few guidelines exist to definitively guide treatment; as a result, practice variation exists. This variation may lead to care inefficiencies with adverse outcomes. We therefore aimed to conduct a patient-level exploration of metastatic gastric cancer management costs, by treatment strategy, and identify predictors of cost. Methods: We performed a patient-level cost analysis of metastatic gastric cancer patients diagnosed between 2005 and 2008 using a 26-month time horizon and the healthcare system’s perspective. Clinical data was derived from a provincial chart review. Costs associated with supportive care, radiation only, chemotherapy only, chemoradiation, gastrectomy, and gastrectomy with chemotherapy +/- radiotherapy were derived using administrative data from a universal healthcare system. Costs were inflated to 2017 United States dollars (USD) Linear regression was used to identify factors predictive of cost. Results: The absolute mean costs of metastatic gastric cancer management increased with increasing level of intervention and ranged from $34,002 to $72,778 (USD); supportive care was associated with the lowest costs and gastrectomy with chemotherapy +/- radiotherapy was associated with the highest costs. Age over 70 and lower Charlson Comorbidity Index were predictors of lower costs while supportive care, radiotherapy, chemoradiation, and gastrectomy were associated with higher costs. Conclusions: Practice variation has known clinical implications, but economic impact also needs to be considered. Variation in the management of metastatic gastric cancer may reflect dissimilar resource availability between health regions as well as differential access to palliative care. Evidence-based guidelines directing appropriate care for metastatic gastric cancer patients to reduce inefficiencies in care and governmental intervention to implement equitable resource allocation to bridge gaps in care are necessary.
Pharmacokinetics (PK) of S-1 monotherapy in plasma and in tears for gastric cancer patients (pts).
Authors: Kawakami Takeshi , Kashiwagi Hiroya , Mori Keita , Omae Katsuhiro , Kasai Jun , Yoshisue Kunihiro , Kawahira Masahiro , Tsushima Takahiro , Machida Nozomu , Fukutomi Akira , Yamaguchi Ken , Yasui Hirofumi 
Published: January 2019

175 Background: S-1 is an oral anticancer drug that contains of tegafur (FT), which is a prodrug of 5-FU, 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate. S-1 is a key, important drug for the treatment of various cancers including gastric cancer. Recently, we demonstrated that Grade 2 or 3 watering eyes was observed in 25% of gastric cancer pts who received S-1 as adjuvant treatment for 1 year (Tabuse H, et al. Gastric Cancer 2017;19:894-901). However, the mechanism of watering eyes caused by S-1 is still unclear. The aim of this study is to investigate the association of the PK of FT, 5-FU, and CDHP, which are components of S-1, in plasma and tears. Methods: We prospectively investigated the PK of FT, 5-FU, and CDHP in plasma and in tears of gastric cancer pts who were treated with S-1 monotherapy at the dose of 80 mg/m2/day. Plasma and tears from both eyes were obtained 1, 2, 4, and 8 hours after S-1 administration on day 1 and 14 of cycle 1. Results: Total of 8 pts were enrolled. PK parameters on day 14 was shown in Table. The concentration of 5-FU in the tears tended to be higher than that in the plasma. There was a strong association between the PK of FT, 5-FU and CDHP in the plasma and that in the tears on day 14 (correlation coefficients r2, right eye/left eye: r2= 0.7778/0.7773, 0.7687/0.7913, and 0.7823/0.7717, respectively). Conclusions: There is a strong association between the PK of FT, 5-FU and CDHP in the tears and that in the plasma. Therefore, the concentration of S-1 in the plasma may be substituted for that in the tears. Clinical trial information: UMIN000021610. [Table: see text]
An evaluation of the surgical treatment strategy for the adenocarcinoma of the esophagogastric junction: A retrospective single center study in Japan.
Authors: Sugita Shizuki , Tokunaga Masanori , Kaito Akio , Watanabe Masahiro , Tonouchi Akiko , Kinoshita Takahiro 
Published: January 2019

177 Background: The incidence of Siewert type II adenocarcinoma of the esophagogastric junction (AEG II) has been increasing in the East, and total gastrectomy (TG) has been a standard treatment procedure.　However, it is reported that the incidence of distal perigastric lymph node (LN) metastasis is low, and thus proximal gastrectomy (PG) could be a treatment option. The aim of this study was to demonstrate the oncological safety of PG for patients with AEG II. Methods: This study included 99 patients with AEG II who underwent gastrectomy with lower esophagectomy from Jan. 2008 to June 2017. Patients with esophageal invasion over 30 mm, and those with positive LN in the upper/middle mediastinum were excluded. PG was selected when more than half of the stomach could be preserved, and no obvious distal perigastric LN metastasis was found. Surgical approach was selected at the patients’ discretion. Short- and long-term outcomes were compared between patients who underwent TG (N = 43) and PG (N = 56). Results: Laparoscopic surgery was the predominant procedure (75.0%) in the PG group while open surgery was most frequently selected (79.1%) in the TG group. Intraoperative and short-term surgical outcomes were not different between the groups except for intraoperative blood loss, which was less in the PG group than in the TG group. Survival outcomes tended to be better in the PG group than in the TG group (3-/5-year OS, 91.1%/ 91.1% vs 67.4%/ 65.1%), presumably due to the predominance of early stage cancers in the PG group. After stratification by pStage, however, survival outcomes were not significantly different between the groups in any pStage. In the PG group, distal perigastric LN reccurence was not found during the follow-up period. In the TG group, 2 patients (4.7%) had distal perigastric LN metastasis, and both died within 2 years of surgery. Conclusions: Therapeutic value of distal perigastric LN dissection is quite limited in patients with AEG II. PG seems to be as oncologically safe as TG, and could be a suitable treatment strategy for patients with AEG II.
First-line chemotherapy with docetaxel, oxaliplatin, and timed-flat infusion 5Fluorouracil in metastatic gastro-esophageal adenocarcinomas: The experience with FD/FOx regimen.
Authors: Cortellini Alessio , Parisi Alessandro , Cannita Katia , Napoleoni Luca , Lanfiuti Baldi Paola , Venditti Olga , Porzio Giampiero , Ficorella Corrado 
Published: January 2019

178 Background: Triplet chemotherapies, with fluoropyrimidines, platin derivates and Docetaxel, represent an option for first line treatment of metastatic Gastro-Esophageal Adenocarcinoma (mGEA). To increase tolerability and dose intensity (DI), we previously developed an alternative way of administration of 5Fluorouracil (5FU), with nocturnal “timed-flat infusion” (TFI) (from 10:00 PM to 10:00 AM), without 5FU bolus and Folinic Acid, in several combination-schedules in breast and colorectal cancers. Methods: We report a retrospective analysis of 27 mGEA patients (pts) treated with FD/FOx regimen, a schedule of weekly TFI/5FU for two nights at 1000 or 900 mg/m2/night, associated to alternating Docetaxel at 50 mg/m2 on days 1 and 15, and Oxaliplatin at 80 mg/m2 on days 8 and 22, cycles repeated every 4 weeks. Results: From June 2007 to July 2017, 17 pts (62.9%) were treated with standard FD/FOx and 10 pts (37.1%) with modified FD/FOx (defined by any projected dose reduction compared to standard) due to age, PS and comorbidities. Median age was 60 years (range 41-80), male/female ratio 19/8, ECOG-PS 0, 7 (26%), 1, 16 (59%), 2, 4 (15%); 17 pts (62.9%) had a Cumulative Illness Rating Scale Intermediate stage, 1 patient (3.7%) a Secondary one. Thirteen pts (48%) had unresected primary tumor. ORR, median PFS and median OS were 73.9% (α0.05, CI±18), 13 and 16 months, respectively. The only G4 toxicity was neutropenia (11.1%); G3 were: neutropenia (29.6%), asthenia (22.2%), diarrhea (22.2%); most relevant G2 toxicities were: nausea (33.3%), anorexia (40.7%), neuropathy (37.0%) and anemia (40.7%). No febrile neutropenia was observed. The received (r)DI were 80% of standard full dose of each drug: Docetaxel 20 mg/m2/week, Oxaliplatin 32 mg/m2/week and 5FU 1440 mg/m2/week. Out of 21 pts who progressed to FD/FOx, 13 pts (48.1%) underwent a second line therapy (6 rechallenges with taxanes). Conclusions: Even if requires a careful management, FD/FOx is a feasible option for first line treatment of mGEA pts, particularly in needing of tumor shrinkage, with significant activity, high rDIs, and acceptable safety profile when compared to literature.
Comparative study of transhiatal and transthoracic thoracoscopic esophagectomy results in adenocarcinoma of the esophagogastric junction.
Authors: Takeda Flavio Roberto , Cecconello Ivan , Ribeiro Ulysses , Sallum Rubens Antonio Aissar 
Published: January 2019

185 Background: The surgical treatment of adenocarcinoma of the esophagogastric junction surgical treatment (AGEJ) is still controversial, particularly concerning to survival and postoperative complications. To compare thoracoscopic esophagectomy (group A) with transhiatal esophagectomy (group B) in patients with AGEJ in relation to the occurrence of complications and mortality; number of ressected lymph nodes, the positive and the ratio between the ressected and positive; overall and disease free survival; and survival after relapse. Methods: There was a selection of 147 patients from 2000 to 2017. Epidemiological data were analyzed and compared between the groups. Postoperative complications were evaluated. The anatomopathological staging was evaluated, analyzing the resected lymph nodes. Analysis of overall survival, disease free survival and survival after relapse were made, besides multivariate analysis of survival related factors. Results: In relation to the complications, group A presented greater occurrence of hoarseness and surgical infections. In relation to mortality, group A presented 2 cases (3.7%) and group B presented 4 (4.3%), without statistical difference. In group A, the average number of ressected lymph nodes was 31.88 and in group B was 20.73 (p < 0.001), however the average number of affected lymph nodes was 3.96 in group A and 4.25 in group B. The general overall survival was 42.3%, in group A was 38.9% and in group B was 47.6% (p = 0.298). In the multivariate analysis of overall survival only lymphatic invasion (p = 0.005), diabetes mellitus (p = 0.038) and surgical infection (p-0.001) were significant. However, in tumors with stage until 2B, group A overall survival was 80.4% and group B was 38.5% (p = 0.001). Conclusions: Both methods are safe with similar morbidity and mortality rates. Transthoracic thoracoscopic esophagectomy allows a larger ressection in the number of lymph nodes. Overall survival and disease free survival are similar, however until stage 2B thoracoscopic esophagectomy improves overall survival. Diabetes and lymphatic invasion interfere in overall and disease free survival.
Development of new endoscopic irreversible electroporation ablation device: Animal experimental study.
Authors: Min Geeho , Choi Hyuk Soon , Kim Woojung , Choi Seong ji , Lee Jung Min , Kim Seung Han , Lee Jae Min , Kim Eun Sun , Keum Bora , Jeen Yoon Tae , Lee Hong Sik , Chun Hoon Jai , Kim Chang Duck 
Published: January 2019

188 Background: Irreversible electroporation (IRE) is a promising novel technique for the ablation of tumors. An advantage of IRE is its mechanism to remove undesired cells by affecting the cell membrane without thermally destructing blood vessels, nerves and the surrounding tissues. Several clinical trials for applying IRE to human organs such as liver, pancreas, and kidney are conducted and studies about IRE ablation for gastrointestinal tumors also have been conducted recently. Here, we developed new endoscopic IRE device, and studied about its effectiveness and feasibility in animal model. Methods: Newly developed endoscopic IRE ablative catheter works with single channel of endoscope. A pair of dipolar electrodes consist of pre-shaped f 0.63mm nitinol wire and the distance between each electrode is 10 mm. The electrodes are loaded within braided tube for stent delivery system then deployed when IRE catheter put in stomach through the endoscope. We performed endoscopy and IRE ablation was done on pig’s stomach mucosa by using endoscopy with newly developed IRE catheter. We divided pig’s stomach into 2 parts(antrum & body), and IRE ablation was applied on each part of the stomach. Pigs were sacrificed after 24hours, and we collected their stomachs with surgical technique. Following fixation, tissues were stained with H&E. Results: Ten male Yorkshire pigs and in vitro stomachs were used in this study. The tissue with H&E stain showed diffuse cell death 24hr after IRE ablation. Consistent with the mechanism of action of IRE on the cell membrane only, there was complete cell death within the IRE lesions without intervening live cells. But there was no difference in histology depending on gastric part in which ablation was applied. During the study, no complication was observed in pigs in 24 hours after ablation. Conclusions: The new endoscopic IRE device, which can perform IRE ablation on gastrointestinal tract using endoscopy showed safe and feasible result.
Clinical significance of surgical treatment for imatinib-resistant gastrointestinal stromal tumors.
Authors: Hashimoto Tadayoshi , Takahashi Tsuyoshi , Kurokawa Yukinori , Kato Ryo , Wada Noriko , Tanaka Koji , Miyazaki Yasuhiro , Makino Tomoki , Yamasaki Makoto , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro 
Published: January 2019

189 Background: The standard first-line treatment for unresectable metastasis or recurrence gastrointestinal stromal tumors (GIST) is imatinib mesylate(IM), a selective tyrosine kinase inhibitor. Although IM has markedly improved the prognosis of patients with advanced GIST, half of the patients experience tumor progression within two years because of resistance to IM. And IM-resistant GIST is basically treated by other kind of TKI, in addition, surgical treatment can be considered as one of treatment options. The aim of this study was to clarify the significance of surgical treatment for IM-resistant GIST in the era of second-line TKI treatment. Methods: We retrospectively analyzed consecutive 35 GIST patients who have developed IM-resistance between 2004 and 2015. We assessed clinicopathological characteristics, postoperative outcomes, imatinib-failure free survival(IFFS), and overall survival(OS) in patients who underwent surgical resection for the IM-resistant lesions. Results: The study enrolled 24 male patients and 11 female patients. The median [range] age was 61 [39-83] years. The primary sites were stomach / small intestine / duodenum: 16 / 14 / 5 cases and resection for primary sites was performed in 32 cases. The median [range] period of IM administration until resistance was 26 [2-119] months, and the resistant lesion sites were liver / peritoneum / primary lesion / local recurrence / bone: 17 / 18 / 2 / 1 / 1 cases (with duplication). Resection for resistant lesions was performed in 18 cases (51%), of which 13 cases (72%) underwent R0 / 1 resection. The postoperative complications ( > Clavien-Dindo classification Grade II) were observed in 3 patients: Biliary leakage, abdominal abscess, and diaphragmatic hernia. IM was resumed promptly after surgery in all 18 patients who underwent resection for IM-resistant lesions, and the median [range] period of IM administration was 22.2 [0.9-56] months. In 5 cases, multiple surgical treatments were performed and second-line TKI was administered in all except for two patients who have still been treated as IM. The median OS was 49 months. Conclusions: It was suggested that surgical treatment for IM-resistant GIST may be safe and effective for appropriate cases.
The impact of the chemoradiation to surgery interval on pathological complete response: Short and long-term overall survival in esophageal cancer patients.
Authors: Azab Basem , Picado Omar , Ripat Caroline , Macedo Francisco Igor , Livingstone Alan S , Franceschi Dido , Yakoub Danny 
Published: January 2019

2 Background: The association of the interval between neoadjuvant chemo-radiation and surgery (CRT-S), and cancer outcomes in patients with esophageal cancer is not clear. We aimed to determine the relationship between CRT-S interval and pathological complete response rate (pCR), short and long overall survival (OS). Methods: Patients listed on the National Cancer Data Base from 2004 to 2013 were studied. We included patients with CRT followed by surgery in 15-90 days. All patients had reported pT, pN cancer stages and survival status. CRT-S interval was studied as continuous (weeks) and categorical variables (quintiles). Results: A total of 5181 patients were included; 81% were adenocarcinomas, 84% were males and mean age was 62 years. They were divided into CRT-S interval quintiles (15 to 37, 38 to 45, 46 to 53, 54 to 64 and 65 to 90 days) (n = 1016, 1063, 1081, 1083 and 938 patients), respectively. There was a significant increase of pCR rate across the CRT-S quintiles (18%, 21%, 24%, 25% and 29%, p < 0.001). This advantage persisted when CRT-S was measured as continuous variable in weeks (OR: 1.11, 95% CI = 1.078-1.143, p < 0.001). However, 90-day mortality significantly increased as CRT-S increased across quintiles (5.7%, 6.2%, 6.8%, 8.5% and 8.2%, p = 0.02) and through weeks (OR = 1.05, 95%CI = 1.005-1.106, p = 0.03). Mean OS across CRT-S quintiles was 59.2, 58.8, 55.4, 56.6 and 51.5 months, respectively. Multivariate Cox regression showed significantly worse OS per week increase in CRT-S interval (HR 1.02, 95% 1.003-1.037, p = 0.02), especially among the last quintile (CRT-S = 65-90 days: HR 1.2, 95% CI 1.04-1.32, p = 0.009). Those with no-pCR had worse OS as time to surgery increased (p < 0.001), while pCR group had similar OS across CTR-S intervals. Conclusions: Despite higher pCR rate as CRT-S interval increasing, surgery is preferred to be done in less than 65 days after CRT to avoid worse 90-day mortality and achieve better OS. Further randomized studies are needed to consolidate our findings.
Phase II LAPACT trial of nab-paclitaxel (nab-P) plus gemcitabine (G) for patients with locally advanced pancreatic cancer (LAPC).
Authors: Hammel Pascal , Lacy Jill , Portales Fabienne , Sobrero Alberto F. , Pazo Cid Roberto A. , Manzano Mozo Jose Luis , Terrebonne Eric , Dowden Scot D. , Shiansong Li Jack , Ong Teng Jin , Nydam Thom , Philip Philip Agop 
Published: January 2019

204 Background: In the phase 3 MPACT study, treatment with nab-P + G resulted in a > 3-fold reduction in primary pancreatic tumor burden vs G in patients with metastatic PC, suggesting the potential for activity against LAPC. This international, multicenter single arm, phase 2 trial (LAPACT) was designed to evaluate the efficacy and safety of an induction phase regimen of nab-P + G in previously untreated patients with LAPC. Methods: Treatment-naive patients with unresectable LAPC and Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 were enrolled. The induction phase was designed as 6 cycles of nab-P 125 mg/m2 + G 1000 mg/m2 on D 1, 8, and 15 of each 28-day cycle. After induction, patients without progressive disease or unacceptable adverse events were eligible for continued treatment with nab-P + G, chemoradiation, or surgery per investigator’s choice (IC). Surgery could occur prior to completing 6 induction cycles if the investigator deemed there had been a sufficient tumor response. The primary endpoint was time to treatment failure (TTF) in patients treated with nab-P + G as induction therapy followed by IC treatment. Key secondary endpoints included disease control rate (DCR), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results: Of 107 patients enrolled, 106 were evaluable for the safety analysis. No new toxicities were identified. The most common grade ≥ 3 treatment-emergent adverse events during induction were neutropenia (42%), anemia (11%), and fatigue (10%); grade 3 peripheral neuropathy occurred in 4% of patients. The most frequent reasons for discontinuing induction were adverse events (18%) and progressive disease (7%). Forty-six (43%) patients received IC treatment after induction: 13 (12%) continued nab-P + G, 17 (16%) received chemoradiation, and 16 (15%) underwent surgical resection (R0, n = 7; R1, n = 9). DCR and ORR during induction were 78% and 35%, respectively; with a median TTF of 8.6 months and median PFS of 10.2 months. Conclusion: A nab-P + G induction regimen in LAPC appears tolerable and feasible and is associated with encouraging antitumor activity and promising TTF and PFS. NCT02301143. Clinical trial information: NCT02301143.