bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can recurrence patterns after curative resection for gastric adenocarcinoma (GCa) inform the selection of adjuvant treatment?
Authors: Luu Shelly , Swett-Cosentino Jossie , Shan Shubham , Tung Stephanie , Siddiqui Mina , Ringash Jolie , Brar Savtaj Singh , Coburn Natalie , Swallow Carol Jane 
Published: January 2019

136 Background: Despite improvements in multidisciplinary care and surgical technique, ≈40% of patients recur after curative resection for GCa. Adjuvant treatment decisions should be informed by the expected timing and site of failure, but accurate data are limited. The aim of our study was to describe and analyze the patterns of recurrence at our center. Methods: Patients who underwent curative intent margin-negative resection from 2006-16 were identified from a prospective GCa database. Date of first detection and site of recurrence were determined. Survival curves were calculated by the KM method. Univariate and multivariable analyses (MVA) were performed to identify predictive variables. Significance was set at p < 0.05. Results: Of 123 patients who met inclusion criteria, median age was 70 yrs, 37% were female, and median follow-up after resection was 24 mos (IQR 11-40). Five-year OS was 72% and RFS 69%. In 34 of 36 patients who recurred, recurrence was detected within 2 yrs. Receipt of adjuvant therapy (Macdonald or MAGIC) was associated with better 5-year OS and RFS than surgery alone (79% vs. 60%, 77% vs. 60%) and delayed time to recurrence (median 10.4 vs. 7.1 mos). Receipt of CRT by the Macdonald protocol appeared to lower the risk of locoregional recurrence vs. surgery alone (see Table) despite routine D2 lymphadenectomy. On MVA, recurrence at any site was predicted by age £ 60y (OR 3.8), male gender (4.0), and AJCC stage > II (4.6). Peritoneal recurrence was predicted only by age £ 60y (3.2). Conclusions: Recurrence after curative resection occurred within 2 yrs of resection. Locoregional recurrence was uncommon in patients who received postoperative CRT. Peritoneal recurrence, which might be abrogated by prophylactic HIPEC at the time of resection, is not well explained by clinicopathologic variables, and novel molecular predictors are required. [Table: see text]
Phase 1b/2 study of margetuximab (M) plus pembrolizumab (P) in advanced HER2+ gastroesophageal junction (GEJ) or gastric (G) adenocarcinoma (GEA).
Authors: Catenacci Daniel V.T. , Park Haeseong , Lockhart A. Craig , Gold Philip Jordan , Enzinger Peter C. , Nordstrom Jeffrey L. , Hong Sam , Hochster Howard S. , Kelly Ronan Joseph , Uronis Hope Elizabeth , Bendell Johanna C. , Oh Sang Cheul , Park Se Hoon , Kim Yeul Hong , Kang Yoon-Koo , Lee Keun-Wook , Ng Matthew CH , Wigginton Jon M. , Davidson-Moncada Jan Kenneth , Bang Yung-Jue 
Published: January 2019

140 Background: Trastuzumab (T) + chemotherapy (ctx) is standard for 1st line advanced HER2+ GEA, yet subsequent targeted options are lacking. M is an anti-Her 2 monoclonal antibody with an optimized Fc domain to increase affinity for activating CD16A Fc-receptors (FcR) on NK cells. Outcomes for T-treated patients (pts) carrying the low-affinity CD16A-F allele are generally worse than pts homozygous for the high-affinity V allele. M is designed to be FcR genotype independent. Evidence of clinical activity of M alone has been seen in HER2+ GEA pts post T, while P has demonstrated durable activity. Loss of HER2 amplification may occur after T failure in a subset of initially HER2+ GEA pts. Preclinical studies suggest that engagement of innate and adaptive immunity with the combination of anti-HER-2 antibodies and T-cell checkpoint inhibition could achieve greater antitumor activity than either agent alone. Methods: Advanced HER2+, PD-L1-unselected GEA pts post T failure were eligible. Dose escalation evaluated 10 and 15 mg/kg M and 200 mg P for 2nd line or higher pts. Cohort expansion evaluates safety and objective response rate (ORR) by RECIST v1.1 in 2nd line pts. M + P is given every 21 days; response assessed every 6 weeks. HER2 amplification status was assessed in a subset of pts by plasma circulating tumor (ct) DNA analysis prior to Cycle 1 of M+P. Results: Dose escalation enrolled 9 pts; cohort expansion 48 pts at 15 mg/kg M: 30 in North America (NA) and 18 in Asia (A). Treatment was well tolerated, with 1 drug-related serious adverse event. Of 38 evaluable pts to date in expansion (24 NA and 14 A), the best overall responses include 7 pts (18.4%) with PR (4 confirmed and 3 unconfirmed) and 11 (28.9%) with SD. Higher ORR trends were observed in A vs NA (35.7% vs 8.3%) and G vs GEJ (31.6% vs 5.3%). Of 25 pts with ctDNA results, HER2 amplification detection was higher in GC than GEJ (80% vs 53%). Responses were independent of FcR genotype; CD16A genotype for evaluable pts with PR: 1 V/V, 2 V/F, 2 F/F with similar allelic distribution among non-responders. Conclusions: M+P is a well-tolerated ctx-free regimen that has shown preliminary antitumor activity in 2nd line pts with advanced/metastatic GEA. Clinical trial information: NCT02689284.
Patterns of recurrence and outcomes after curative resection of locally advanced HER2-positive gastroesophageal cancer (HPGEC).
Authors: Jiang Di Maria , Lim Charles Henry , Ma Lucy Xiaolu , Sun Peiran , Sim Hao-Wen , Natori Akina , Chan Bryan Anthony , Yokom Daniel , Moignard Stephanie , Chen Eric Xueyu , Liu Geoffrey , Knox Jennifer J. , Swallow Carol Jane , Darling Gail Elizabeth , Brar Savtaj Singh , Hafezi-Bakhtiari Sara , Conner James , Jang Raymond Woo-Jun , Elimova Elena 
Published: January 2019

147 Background: Literature on recurrence and outcomes of HPGEC is scarce. The aim of this study was to determine pattern of recurrence and outcomes after curative intent surgery for locally advanced HPGEC. Methods: A retrospective database was used to identify consecutive patients with gastroesophageal adenocarcinomas undergoing curative intent resection between 2011 and 2016 at the Princess Margaret Cancer Centre. Clinico-demographic data were extracted from the electronic health record. Patterns of relapse are classified as nonvisceral (defined as recurrences in the bone, peritoneal or both), visceral (not nonvisceral, including the brain), or both. Time to relapse (TTR) and overall survival (OS) were calculated from date of histologic diagnosis. Results: Of 45 patients with HPGEC, 78% were male, and 91% were non-Asian. Median age was 64.4 years (interquartile range [IQR] 53, 70); 60% were gastroesophageal junction, 24% were gastric, and 16% were esophageal adenocarcinomas; 31% were poorly differentiated tumors while 68% had clinical or pathological node positive disease. Complete R0 resection occurred in 93%, and 84% had received perioperative therapy (31% with perioperative chemotherapy; 40% with pre-operative chemoradiation; 9% with post-operative chemoradiation). With a median follow-up time of 26.0 months. relapse rate of HPGEC at last follow-up was 78%. Among first relapses, 94% were distant, while 6% were local recurrences. Among distant relapses, visceral recurrences occurred in 85%, nonvisceral in 3%, and 12% patients had both visceral and nonvisceral recurrences. None had peritoneal only recurrence. Median TTR was 12.2 months (IQR 8.8, 23.5), while median post-recurrence survival was 9.7 months (IQR 4.7, 16.3). Of the entire cohort, 2-year OS was 53% and 3-year OS was 26%. Conclusions: More than three-quarters of patients with HPGEC experienced recurrence after curative intent multimodality therapy. Our results suggest that HPGEC rarely relapse with peritoneal only disease or local recurrence, thereby calling into question the utility for aggressive surveillance, pending verification from larger cohorts.
Robotic-assisted (RAMIE) x thoracoscopic esophagectomy (MIE): Comparison on safety and lymph nodal dissection in 181 cases.
Authors: Sallum Rubens Antonio Aissar , Takeda Flavio Roberto , Santo Marco Aurelio , Cecconello Ivan 
Published: January 2019

150 Background: Robotic-assisted esophagectomy (RAMIE) gained evidence among the major oncological procedures due possibilities on lymph nodal dissection. The concept of esophagectomy and extensive lymphadenectomy with low morbidity boosted by the videothoracoscopic esophagectomy(MIE) is now focused on the robotic approach. Methods: The first 37 cases of RAMIE were studied. The thoracic field performed in the prone position with three robotic arms and abdominal field idem, as performed in the upper GI robotics procedures. Conversion to open or laparoscopic procedures, morbidity and mortality as well as the length of the lymphadenectomy were evaluated. These data were compared to the first 154 cases of MIE operated by the same surgical team in those early results. Also the late survival of the MIE group is presented. Results: All except 2 RAMIE cases were Siewert I or II Adenocarcinoma, 32 post neoadjuvancy: MAGIC (7) or CROSS (25). There was no conversion to lap or open procedures. No patient received blood transfusion. One complication was observed: a partial rotation of gastroplasty in the thorax, that required thoracoscopic approach in the day 7. Mortality (90 days) was zero. Mean resected lymph nodes was 42.5 (30-76). In the MIE group, complications were: respiratory (26.2%), infectious (8.4%), cervical fistula (17.7%), vocal cord palsy (8.4%). 30 and 90 days mortality were one (0.93%) and 3 (2.8%). Mean dissected lymph nodes = 31.6 (± 14.3), 1:57 positives (± 3.21) and RAD 00:05 (± 0:09). The overall five-year survival was 69% (95% CI: 57% - 83%), 75% in stage 0 / I / II and 42% in III/IV. Conclusions: RAMIE with these technical proposal, seams to be safe without mortality. Lymph nodal achieved was equal to greater than the practiced through MIE. After those cases we started a randomized prospective trial on this issue (NCT02292914).
HER-2 overexpression in gastroesophageal junction (EGJ) adenocarcinoma as a predictor of prognosis in patients treated with perioperative chemotherapy.
Authors: Felismino Tiago , Oliveira Audrey , Alves Ana Caroline , Jesus Victor Hugo Fonseca , Costa Wilson L. , Coimbra Felipe José Fernandez , De Barros E. Silva Milton Jose , Riechelmann Rachel Pimenta , Begnami Maria Dirlei , Rodrigues Newton Augusto Ferreira , Mello Celso Lopes 
Published: January 2019

151 Background: Approximately 15% of all gastroesophageal adenocarcinomas overexpress HER-2. This is more common in intestinal subtype and proximal tumors. HER-2 status is associated with poor prognosis in non-metastatic patients, but its prognostic impact on the outcomes of pts treated with perioperative chemotherapy (CT) is unclear. Methods: The aim of this study was to retrospectively analyze the influence of HER-2 status on the overall survival (OS) and Relapse Free Survival (RFS) of pts with locally advanced gastroesophageal adenocarcinoma treated with perioperative CT. HER-2 positive tumors were defined by 3+ immunohistochemical staining or fluorescence in situ hybridization positivity. Independent variables used in the Cox model were: Lauren's subtype, clinical staging, and a combination of primary site and HER-2 status. Results: A total of 97 patients were included: median age was 62y, 62 (63.9%) were male; N = 57 (58.8%) had cT3 tumors and 60 (60.1%) had cN+. Lauren’s subtype was intestinal in N = 35 (36.1%), and diffuse in N = 44 (45.4%). CT regimens were mainly FOLFOX (46.4%), EOX (23.7%) or DCF (13.4%). Regarding primary site and HER-2 status: gastric HER-2 negative N = 61, Gastric HER-2 positive N = 8, GEJ HER-2 negative N = 23, GEJ HER-2 positive N = 5. In a Cox multivariate analyses for OS and RFS, EGJ HER-2 positive pts had higher chance of recurrence (HR = 3.57, 1.08 – 11.77, p = 0.03) and death (HR = 6.14, 1.83 – 20.60, p = 0.003). EGJ HER-2+ 3y RFS was zero and 3y OS was 20%. Conclusions: EGJ HER-2+ tumors carried a dismal prognosis and had little benefit from conventional perioperative CT strategies. Although further studies are needed to confirm our data, we believe that a different approach, possible combining anti-HER-2 drugs, should be tested in this scenario.
Efficacy of cytotoxic agents after progression of anti-PD-(L)1 antibody for pretreated metastatic gastric cancer.
Authors: Kato Kyoko , Narita Yukiya , Mitani Seiichiro , Honda Kazunori , Masuishi Toshiki , Taniguchi Hiroya , Kadowaki Shigenori , Ura Takashi , Ando Masashi , Tajika Masahiro , Muro Kei 
Published: January 2019

152 Background: The efficacy of anti-PD-1 antibody for metastatic gastric cancer (mGC) was revealed. In non-small cell lung cancer (NSCLC), it was reported that overall response rate (ORR) in patients (pts) treated with chemotherapy (CTx) after immunotherapy exposure was higher than historical data from the pre-anti-PD-(L)1 era. The purpose of this retrospective study was to evaluate whether CTx improved efficacy outcomes after exposure anti-PD(L)1 antibody in mGC. Methods: We investigated retrospectively clinical characteristics at baseline of mGC pts who received CTx after progression of anti-PD-(L)1 antibody between April 2014 and August 2017. Anti-PD-(L)1 antibody was adapted as third- or later-line therapy. Pts fulfilled following criteria: histologically proven adenocarcinoma; ECOG PS 0-2; adequate organ functions; and received CTx including fluoropyrimidines (FU), platinum, and taxane or irinotecan. We evaluated efficacy outcomes, including ORR, disease control rate (DCR), time to treatment failure (TTF), and overall survival (OS). Results: Out of 40 treated with anti-PD-(L)1 antibody, 15 pts were included. Patient characteristics were as follows: median age (range), 67 (46-83) years; male/female, 13/2; ECOG PS (0/1/2), 5/8/2; HER2 positive, 8; histology (differentiated/undifferentiated), 10/5; metastatic lesions (peritoneum/liver/lung), 4/8/3; number of metastatic sites (1/≥2), 2/13; number of prior CTx regimens (3/4/5), 2/9/4; median period (range) from first line CTx, 30.7 (12.7-68.1) months; and CTx regimens (FU+oxaliplatin/taxane/irinotecan), 10/3/2. ORR, DCR, median TTF, and OS were 33% (95% CI, 15.2-58.3), 87% (95% CI, 62.1-96.3), 3.5 (95% CI, 1.6-4.4) months, and 7.6 (95% CI, 4.4-8.5) months, respectively. There were no predictive and prognostic factors associated with ORR, TTF, and OS on univariate analysis. At the beginning of CTx, 4 pts had immune-related adverse events (irAEs), but these were manageable and no new irAEs appeared during CTx. Conclusions: Our data support further evaluation of the use of CTx after progression of anti-PD-L 1 antibody, even in heavily pretreated mGC pts. Updated results will be presented.
Systemic chemotherapy for gastric cancer with early recurrence after adjuvant S-1 monotherapy: A multicenter retrospective study.
Authors: Hasegawa Hiroko , Mitani Seiichiro , Wakatsuki Takeru , Hara Hiroki , Hirao Motohiro , Takahari Daisuke , Chin Keisho , Kadowaki Shigenori , Muro Kei 
Published: January 2019

154 Background: S-1 monotherapy is one of the standard adjuvant treatments for stage II or III gastric cancer patients (pts). Early recurrence after adjuvant therapy has a poor prognosis and the optimal regimen remains to be established. This study aimed to clarify the treatment outcomes of systemic chemotherapy and explore encouraging regimens for gastric cancer pts with early recurrence. Methods: We retrospectively reviewed gastric cancer pts at four institutions who underwent curative gastrectomy followed by adjuvant S-1 monotherapy and identified pts who developed recurrence during the adjuvant therapy or within 6 months after completion between 2005 and 2015. Other main eligibility criteria were Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0-2, adequate organ function and no massive ascites. The Cox proportional hazards model was used to evaluate the survival outcomes, adjusting for relevant factors. Results: A total of 112 pts were included. Pts characteristics were as follows: median age (range), 62 (29-83) years; male/female, 84/28; ECOG-PS 0/1/2, 39/63/10; diffuse/intestinal, 73/39; HER2 status positive/negative/unknown, 17/46/49; metastatic site liver/peritoneum, 32/44; and number of metastatic sites 1/≥2, 94/18. The taxane-based regimens were as follows: weekly paclitaxel (PTX) (38), nab-PTX (4), trastuzumab (Tmab) + PTX (4), S-1 + PTX (3), and the others (4). The platinum-based regimens were irinotecan + cisplatin (IP) (31), capecitabine + cisplatin (XP) (7), S-1 + cisplatin (5), Tmab + XP (4), and the others (2). For all pts, the median PFS and OS were 3.7 months (M) and 11.4 M, respectively. After excluding HER2-positive pts, there were no statistically significant differences between the taxane-based and platinum-based regimens in survival outcomes (median OS, 7.6 M vs. 12.2 M; adjusted HR = 0.93, 95% CI 0.58-1.49), nor between IP and the other platinum-based regimens (median OS, 11.8 M vs. 13.3 M; adjusted HR = 0.64, 95% CI 0.28-1.46). Multivariate analysis showed treatment regimen was not a prognostic factor. Conclusions: The regimens so far selected for gastric cancer with early recurrence resulted in similar, poor prognosis.
Treatment strategy for lateral spreading superficial esophageal squamous cell carcinoma.
Authors: Kawakubo Hirofumi , Suda Koichi , Mayangai Shyuhei , Nakamura Rieko , Wada Norihito , Kitagawa Yuko 
Published: January 2019

169 Background: ESD is the one of the options of treatment even for lateral spreading (size is over 5 cm) esophageal squamous cell carcinoma (L-S ESCC). Some patients have to undergo additional treatment because tumor is invaded to submucosal layer or lymphovascular invasion. On the other hand, wide resection by ESD could cause the delay of additional treatment because of the treatment for esophageal stricture after ESD. Thus, treatment strategy for L-S ESCC has to include additional treatment after ESD. Methods: From January 2010 to December 2014, 49 cases of l L-S ESCC were resected by surgery or ESD. Diagnosis, treatment methods and outcomes are evaluated. Results: In 49 cases of L-S ESCC, 32 cases were treated by ESD and 17 case were treated by surgery. Average size of tumor treated by ESD is 59.4 mm(50-85 mm). Accuracy of estimated depth of invasion by endoscopy for ESD cases is 65.7%. Four of 32 cases of ESD underwent additional therapy (3 for surgery and 1 for CRT) because of pT1b (SM2) or lymphvascular invasion, and one case has lymph-node metastasis. Rate of stricture after ESD is 20.0% for sub-circumference ESD and 77.8% for circumference ESD instead of steroid injection. Average time and duration for control of esophageal stricture by Balloon Bougie is 13.5 times and 18 weeks. Average size of tumor treated by surgery is 76.5 mm(50-130 mm). Accuracy of estimated depth of invasion by endoscopy for surgical cases is 47.1%. Seven cases in 17 (41.2%) have lymph node metastasis. One case died by recurrence after surgery and 48 cases were survived without any recurrences. Conclusions: Accuracy of estimated depth of invasion by endoscopy for L-S ESCC is cute low compared to normal superficial ESCC. Most of strictures after sub-circumference ESD could be prevented by steroid injection. However control of strictures after circumference ESD is difficult. Thus, diagnostic ESD should not be performed for circumferencial lesions of L-S ESCC for the patients who will select CRT for additional treatment, and CRT should be selected for first treatment of these cases. Long survival could be obtained by ESD or surgery for the patients of L-S ESCC by our treatment strategy.
Enrollment of esophago-gastric cancer patients in a clinical fast-track program and it’s affect on time to treatment and quality of life.
Authors: Burnett Atuhani S. , Mouhanna Jack , Ramirez-Garcialuna Jose , Lee Emma , Breau Julie , Diovisalvi Mary , Alcindor Thierry , Asselh Jamil , Vanhuyse Marie , Alfieri Joanne , David Marc , Mueller Carmen L. , Spicer Jonathan D. , Cools-Lartigue Jonathan , Ferri Lorenzo 
Published: January 2019

180 Background: Esophago-gastric cancers are aggressive malignancies requiring numerous investigations to plan complex multi-modal therapy. The path from initial diagnosis to treatment can be associated with a long delay. This delay and complex patient trajectory may impact quality of life. Given the poor prognosis and highly symptomatic nature of upper GI cancer, a clear and timely access to treatment of crucial importance. We sought to determine the impact of a newly implemented streamlined and structure interdisciplinary pathway for newly diagnosed esophageal and gastric cancer on access times to treatment and quality of life (QoL). Methods: A streamlined pathway for patients referred to a high volume Upper GI Cancer clinic was generated with input from physicians, nutritionists, specialized nurses, and social workers. New diagnosis of esophageal or gastric cancer from 2014-16 were enrolled in this program and consenting patients completed serial QoL questionnaires (ESAS) at baseline, pre-treatment, 1 month post treatment. Dysphagia (DS) was quantified on a 5 point scale. Time intervals (days) were evaluated at various points between diagnosis and start of treatment (diagnosis, CT imaging, first visit with upper GI program, start of treatment). Data presented as median(IQR), * p < 0.05. Results: Of the 251 patients with Upper GI cancer, 153 (61%) consented to participate including 140 esophageal/EGJ and 13 gastric cancer patients. Clinical stage distribution was 17.9% I, 30.7% II, 42.6% III, 8.7% IV. Of the 82 Esoph/EGJ patients with completed QoL questionnaires, 15 (18.3%) patients had severe dysphagia (DS = 3-4) and were prioritized for treatment. Patients with severe dysphagia had reduced time from index endoscopy to treatment (29 (16.3-39.3) vs 43 (32.8-68.0)days)* and first Upper GI clinic to treatment (15 (8.0-23.0) vs 25 (21.0-36.0)*. ESAS surveys showed increased QoL for both patients with and without dysphagia from baseline to pre-treatment indicating that simply entry into the streamlined program improved QoL. Conclusions: Structured interdisciplinary investigative and treatment programs for upper GI cancers can expedite time to treatment and improve QoL.