bluuebunny/crossref_metadata_2025 huggingface dataset:
Screening and treatment strategy for double cancer for esophageal cancer surgery patients.
Authors: Ogata Takashi , Shimoda Yota , Kano Kazuki , Koumori Keisuke , Watanabe Hayato , Fujikawa Hirohito , Yamada Takanobu , Oshima Takashi
Published: February 2020

336

Background: Esophageal cancer treatment, especially esophagectomy, is highly invasive, so treatment strategies are considered in view of existing double cancers. On the other hand, in Japan, 90% of esophageal cancers are squamous cell carcinoma, and it is known that there are a large proportion of head and neck cancers for double cancers as field cancerization. Methods: The aim of this study is to investigate the types of double cancer, simultaneous/metachronous, and the frequency and treatment policy of head and neck cancer as a particularly high coexistence rate for esophageal cancer surgery patient. The subjects were 304 patients who underwent esophagectomy performed from April 2010 to December 2017. All patients were examined with high-definition endoscopy with NBI by certificated endoscopist at the first visit as a search for simultaneous double cancer from the pharynx to the stomach. And after esophagectomy, endoscopy was also performed to check for metachronous double cancers in the remaining esophagus, gastric tube, and pharynx at least every 2 years. Results: The number of double cancer cases was found in 94 cases (30.9%), and the total number of double cancer cases was 122. Head and neck cancer(33 cases), stomach cancer(16 cases), and colon cancer(12 cases) were observed as the main course of double cancers. In double cancer cases, 47cases(50.0%) were metachronous, 35cases(37.2%) were simultaneous, and 12cases(12.8%) were both synchronous. The most common double cancer was head and neck cancer(33 cases:35.1%), and 23 cases were simultaneous, 10 cases were metachronous. As treatment strategy for head and neck cancer, endoscopic laryngo-pharyngo surgery(ELPS) were 19 cases. 10 cases(52.7%) were synchronous cancers, and 9 cases (47.3%) were metachronous cancers which were detected during follow-up after esophagectomy. Conclusions: Head and neck cancer associated with esophageal cancer surgery is the most common type of double cancer, and 1/3 of ELPS cases have been detected by follow-up endoscopy after esophagectomy, so endoscopic surveillance was also considered important.
Outcomes of elderly patients with resectable liver metastases from colorectal cancer (CRLM): Single center experience.
Authors: Mansour Laura , Nassabein Rami Mohamad , Gryspeerdt Filip , Vandenbroucke-Menu Franck , Aubin Francine , Ayoub Jean-Pierre M. , Dagenais Michel , Lapointe Real W. , Letourneau Richard , Plasse Marylene , Roy Andre , Turcotte Simon , Tehfe Mustapha
Published: February 2020

34

Background: Half of patients with colorectal cancer develop liver metastases during the course of their disease. Surgery is the only potentially curative option for CRLM if resectable. Treatment of patients over 70 years old is challenging mainly because of comorbidities and other geriatric syndromes. Thus, we intended to report our experience with elderly patients with resectable CRLM. Methods: After approval by the Institutional Review Board (IRB), all records from a prospectively collected database at Centre Hospitalier de l’Université de Monréal (CHUM) were retrospectively analyzed. Clinicopathological characteristics, surgery and chemotherapy treatment modalities were reviewed. RFS and OS in patients ≥ 70y were calculated using the Kaplan Meier survival curve. Results: From 2010 to 2016, 101 patients older than 70 years were identified. Safety and surgical complications were previously reported. Median age was 75 years. CRLM were synchronous in 46.5% and metachronous in 53.5%. Relapse free survival (RFS) of patients ≥ 70 years was 33.7 months. Overall survival (OS) of patients ≥70 years was comparable to those of less than 65 years old (median OS: 56 vs 62 months; p = 0.15, respectively). Hepatic relapse showed worse survival when compared to extra-liver recurrence, mOS: 44 vs 33.2 vs 29.3 months for non-hepatic, hepatic only and hepatic with other sites respectively (trend p = 0.034). Although non-statistically significant, Patients with metachronous CRLM had superior mOS compared to those with synchronous disease (58.7 vs 44.7 months; p = 0.22). Conclusions: Survival Outcomes of patients with an age ≥ 70 years were comparable to those of younger patients and what is reported in literature. Age should not be a limiting factor in the management of elderly patients with resectable CRLM. Hepatic metastatectomies +/- chemotherapy should be offered with curative intents.
Synchronous pulmonary and esophageal cancers: Is combined esophagectomy and anatomic lung resection appropriate?
Authors: Zhao Hedi , Misariu Ana-Maria , Ramirez-Garcia Luna Jose , Hofstetter Wayne Lewis , Molena Daniela , Katz Amit , Nobel Tamar B. , Mueller Carmen L. , Cools-Lartigue Jonathan , Spicer Jonathan , Mulder David S. , Ferri Lorenzo
Published: February 2020

341

Background: Resection is the best treatment for both esophagus and lung cancer, however, concerns that a combined resection of synchronous lung/esophagus tumors might be associated with higher morbidity may preclude surgical therapy. We sought to review a multi-institutional experience on combined esophagus/lung cancer resections. Methods: Patients undergoing esophagectomy and those with concurrent anatomic resection for bronchogenic carcinoma between 1997-2018 at three high-volume North American centers were identified from prospectively collected databases. Combined resection cases (E+L) were matched in a 1:3 ratio to patients who underwent esophagectomy alone (E), based on age, sex, stage, neoadjuvant therapy, procedure (2/3hole), and approach (MIE/open). Patient demographics, tumour characteristics, and post-operative outcomes were compared. Statistical analysis was performed using unpaired t-test or Wilcoxon sum-rank test for continuous variables and Fisher’s exact test for categorical data. Statistical significance was defined as p < 0.05. Results: Of over 2500 patients undergoing esophagectomy, synchronous anatomic lung resection was performed in 20; 4 were excluded due to incomplete data (n = 16). Matching yielded 48 patients and 4 duplicates were removed (n = 44); there were no significant differences in patient demographics, neoadjuvant therapy, clinical stage, or procedure. Anatomic resection consisted of lobectomy (16/20), segmentectomy (3/20) and pneumonectomy (1/20), combined with 2-hole (14/20), 3-hole (4/20), or left thoraco-abdominal (2/20) esophagectomy. The proportion of patients with any complication in E+L was 50%, and 66% in E (p = 0.42). Pulmonary complications were 19% and 27% in the respective groups (p = 0.74). Mortality did not differ (E+L = 0/16:E = 1/44)NS. The median length of stay for both groups was similar (E+L = 10.5 days(IQR 5.7): E = 10.0 days (IQR 8.7))NS. Conclusions: Patients with synchronous localized lung and esophageal cancer, although rare, should not be biased towards non-surgery therapy, as the morbidity associated with combined esophagectomy and anatomic lung resection does not differ significantly from esophagectomy alone.
Variation in treatment patterns and outcomes for resected esophageal cancer at designated thoracic surgery centers.
Authors: Gupta Vaibhav , Levy Jordan , Kidane Biniam , Mahar Alyson , Ringash Jolie , Sutradhar Rinku , Darling Gail Elizabeth , Coburn Natalie ,   PRESTO Research Group
Published: February 2020

343

Background: Ontario regionalized thoracic surgery to designated centers to provide high-volume care for patients undergoing esophageal cancer resection. The objective of this study was to assess variation in treatment patterns and outcomes across thoracic centers, and to compare their performance to non-thoracic centers. Methods: A retrospective, population-based cohort study (2002-2014) was conducted in Ontario, Canada (population 13.6 million). Adults with resected esophageal cancer were identified through the PRESTO database. Case mix, use of neoadjuvant therapy, surgical outcomes (lymph node yield and margin rates) and survival were described across thoracic centers. Multivariable regression was used to estimate the effect of having surgery at a regionalized thoracic surgery center on perioperative (in-hospital & 90-day post-discharge) mortality and long-term survival, adjusting for case mix. Results: Of 3,880 patients meeting study criteria, 2,213 had pathology data available and were included in the analysis. Average age was 64 years, 85.7% had adenocarcinoma, 50.2% were pT3, and 38.4% were pN0. Most (82.6%) had surgery at one of 15 thoracic centers. Across thoracic centers, rates of neoadjuvant therapy varied 16.4-81.6%, positive margin rates varied 8.2-29.6%, median lymph node harvest varied from 7-20 nodes, perioperative mortality varied 2.6-20.5%, and 2-year survival varied from 48-80%. There was a trend toward reduced perioperative mortality, but no difference in long-term survival, with having surgery at a thoracic center. Conclusions: Even at designated thoracic centers, there is significant variability in treatment patterns, surgical outcomes, and survival. Looking beyond center volume, and translating best practices from high-performing hospitals to other hospitals, may improve patient outcomes.
Impact of inaccurate clinical staging for gastric cancer on patient survival outcomes.
Authors: Ju Michelle , Porembka Matthew R.
Published: February 2020

345

Background: Accurate clinical staging (CS) in gastric cancer is critical for appropriate treatment selection and prognostication, but CS remains highly ineffective. Our study aims to evaluate the factors associated with inaccurate CS, the impact of inaccurate CS on patient outcomes, and effect of adjuvant therapy in patients with inaccurate CS. Methods: We conducted a retrospective review of the NCDB of patients diagnosed with clinical early-stage gastric adenocarcinoma based on AJCC 8th edition (cT1-2, N0, M0) between 2004-2016. Those who did not undergo upfront surgery or had missing pathologic staging data were excluded. Patients were classified into 3 groups: accurately staged (AS) if pathologic staging confirmed early-stage cancer, inaccurately staged with receipt of adjuvant therapy (IS+), and inaccurately staged with no receipt of adjuvant therapy (IS-). Logistic regression using stepwise selection was utilized to assess the impact of factors on CS accuracy and receipt of adjuvant therapies. Kaplan-Meier and Cox Proportional Hazard methods were used to compare survival outcomes. Results: Approximately 39% of patients (2841/7199) were understaged. T2 tumors, non-well differentiated tumors, and diffuse type histology were associated with increased likelihood of inaccurate CS. Age >60, female sex, Asian/Black race, and non-cardia tumor location were associated with decreased likelihood of inaccurate CS. Only 44% of patients who were inaccurately staged received adjuvant chemotherapy/radiation. Age >75 and fundus/body tumor location were associated with decreased likelihood of receiving adjuvant therapies, while more advanced pT and pN stage were associated with increased likelihood. Treatment facility type (community vs. academic) had no impact on likelihood of accurate CS or receipt of adjuvant treatment after inaccurate CS. 5-year overall survival was significantly different between groups (71.7% AS, 48.3% IS+, 51.1% AS-; p<0.001). Conclusions: CS is inadequate, and understaging has detrimental effects on patient survival outcomes. Novel strategies for improved CS are needed to improve patient care.
Feasibility and pathological response of TAS-118 + oxaliplatin as perioperative chemotherapy for patients with locally advanced gastric cancer (APOLLO-11).
Authors: Takahari Daisuke , Takashima Atsuo , Nakajima Takako Eguchi , Ishizuka Naoki , Ohashi Manabu , Katai Hitoshi , Mikami Shinya , Chin Keisho , Nunobe Souya , Ito Miki , Wada Takeyuki , Ogura Takashi , Sano Takeshi , Boku Narikazu , Yamaguchi Kensei
Published: February 2020

351

Background: TAS-118 is a novel oral agent, containing S-1 and leucovorin. In the SOLAR study (NCT02322593), TAS-118 + oxaliplatin (OHP) significantly improved overall survival compared to S-1 + cisplatin for patients (pts) with advanced gastric cancer (GC). We conducted this open-label study to assess feasibility of perioperative adjuvant chemotherapy with TAS-118 + OHP in pts with locally advanced resectable GC with lymph node metastasis. (Clinical trial information: UMIN000024688). Methods: Eligible pts who had histopathologically confirmed GC with clinical T3-4N1-3M0 on image findings (14th Japanese classification of gastric carcinoma), age 20 to 79 years, were enrolled in this study. The protocol treatment consisted of preoperative 4 courses of TAS-118 (80-120 mg/body, days 1-7) + OHP (85 mg/m2, day 1) every 2 weeks, and gastrectomy with D2 lymphadenectomy, followed by postoperative 12 courses of TAS-118 alone (step1) or 8 cycles of TAS-118 + OHP (step2). The primary endpoints were tolerability of preoperative chemotherapy, gastrectomy and postoperative chemotherapy with TAS-118 plus OHP. Here, we report the feasibility of preoperative chemotherapy and gastrectomy, and pathological response. Results: Between December 2016 and April 2018, 45 pts with a median age of 61 years were enrolled. The numbers of pts with T stage (cT3/4a) and those with N stage (cN1/2/3) were 13/32 and 25/17/3, respectively. The completion rate of preoperative chemotherapy and gastrectomy was 88.9% ( 95% CI 78.0-95.5) and 95.6% (95% CI 86.7-99.2). The relative dose intensity of TAS-118 and OHP was 86.0% and 90.6%. During the 4 cycles of preoperative TAS-118 + OHP, 2 pts discontinued the treatment due to adverse event (AE). Major grade 3-4 AEs were diarrhea (17.8%) and neutropenia (8.9%). R0 resection rate was as high as 95.6%. One pts experienced grade 4 postoperative bleeding, but no treatment-related death was reported. pCR was achieved in 6/45 pts (13.3%) and other 7 pts (28.9%) showed near complete regression (<10 % residual tumor cells). Conclusions: Preoperative TAS-118 + OHP followed by D2 gastorectomy was well tolerated and showed promising efficacy. Clinical trial information: 000024688.
A phase II trial of cytoreduction, gastrectomy, and hyperthermic intraperitoneal perfusion with chemotherapy for patients with gastric cancer and stage IV peritoneal disease.
Authors: Badgwell Brian D. , Ikoma Naruhiko , Blum Murphy Mariela A. , Wang Xuemei , Estrella Jeannelyn , Roy-Chowdhuri Sinchita , Das Prajnan , Minsky Bruce D. , Mansfield Paul F. , Ajani Jaffer A.
Published: February 2020

361

Background: Current national guidelines do not include hyperthermic intraperitoneal chemoperfusion (HIPEC) as treatment for gastric cancer, and there are no completed clinical trials of cytoreduction, gastrectomy, and HIPEC from the U.S. However, recent international studies report long-term survival rates of approximately 20% with cytoreduction/gastrectomy/HIPEC. Methods: Patients with gastric adenocarcinoma and positive peritoneal cytology or carcinomatosis who had completed systemic chemotherapy and laparoscopic HIPEC underwent cytoreduction, gastrectomy, and HIPEC with 30 mg mitomycin C and 200 mg cisplatin. The primary end point was overall survival (OS), with secondary end points of safety and postoperative complications. Results: We enrolled 20 patients from 9/2016 to 3/2019, with a median age of 58 years (range, 20-75 years). Six patients had positive cytology only at diagnosis of stage IV disease, whereas 14 had carcinomatosis. All patients were treated with systemic chemotherapy with a median of 8 cycles (range, 5-11 cycles) and at least one laparoscopic HIPEC. The median peritoneal carcinomatosis index at cytoreduction/gastrectomy/HIPEC was 2 (range, 0-13). After surgery, the 90-day morbidity and mortality rates were 70% and 0%, respectively. Median length of hospital stay was 13 days (range, 7-23 days). Median follow-up was 1.8 years. Median OS from the date of diagnosis of metastatic disease was 2.1 years. Median OS from the date of cytoreduction, gastrectomy, and HIPEC was 1.4 years. One, 2, and 3-year OS rates from the diagnosis of metastatic disease are 90%, 54%, and 29%. Conclusions: Survival rates for patients with gastric adenocarcinoma and peritoneal disease treated with cytoreduction, gastrectomy, and HIPEC are encouraging; our early results are similar to those of recent prospective registry studies. Cooperative group trials should be supported and will be required to confirm survival and safety outcomes. Clinical trial information: NCT02891447.
The real-world practiсe of surgery in patients with metastatic gastric cancer (mGC).
Authors: Obarevich Ekaterina , Besova Natalia , Titova Tatiana , Trusilova Elena , Davydov Mikhail , Nered Sergey , Stilidi Ivan , Artamonova Elena
Published: February 2020

363

Background: According to recent studies the results of treatment patients with initially mGC are still not sufficient: median overall survival varies between 6.1 and 12.4 months. The triplet-chemotherapy regimens demonstrate high efficacy and allow to downstage the disease and perform surgical treatment. Conversion treatment in stage IV GC is a modern trend and still an area of ongoing research. Methods: We analyzed the efficacy of first line chemotherapy (6-9 courses) for patients with mGC (n = 55) including the following regimens: 1) mFOLFIRINOX; 2) douplet: oxaliplatin/irinotecan + fluoropyrimidine; 3) triplet variations: docetaxel, platinum and fluoropyrimidine. 27/55 patients had > 2 metastatic sites, 2/55 patient - 5 metastatic sites. The most common localizations of metastases were peritoneum (n = 34) and retroperitoneal lymph nodes (n = 11). Unlike in REGATTA trial all patients underwent surgical treatment with curative intent followed by complete response of distant metastases after chemotherapy. For patients with ovarian metastases ovariectomy was also perfomed. Results: Median progression-free survival and median overall survival were 18.5 and 33.27 months, respectively and the 3-year survival rate was 43.5%. Multivariate analysis showed that clinically determined ascites (p = 0.023), linitis plastica (p = 0.022), tumor grade 3 (p = 0.014), present of lymphovascular invasion (p = 0.037), absence of grade III-IV pathomorphosis (p = 0.037) and treatment free interval before surgery < 3.4 month (p = 0.046) were poor independent prognostic factors. Conclusions: Surgery after effective combination chemotherapy may have significant clinical efficacy for selected patients with initially unresectable gastric cancer. According to our data the optimal time for surgery is a 3.4 and more months treatment-free interval in the absence of disease progression.
A phase II study of neoadjuvant chemotherapy with DCS for resectable advanced esophageal cancer.
Authors: Kitadani Junya , Nakamura Masaki , Ojima Toshiyasu , Katsuda Masahiro , Hayata Keiji , Yamaue Hiroki
Published: February 2020

366

Background: The current standard treatment for clinical stage II/III esophageal cancer is neoadjuvant chemotherapy (NAC) with CDDP/5-FU (CF) regimen followed by surgery. However, to improve the survival of patients with advanced ESCC, more effective regimens are urgently needed. Triplet regimens containing docetaxel have been one of next candidates for advanced ESCC. Methods: The DCS regimen (Docetaxel 40mg/m2/day Day 1 div, CDDP 60mg/m2/day Day 1 div, S-1 80mg/m2/day Day 1~14 civ) was repeated every 4weeks until toxicity became unacceptable, the patient refused treatment, or disease progression was observed to a maximum of 3cycles. In this phase II trial of DCS, the primary endpoint was pathological response rate. Results: 40 patients were enrolled in this study and finally 39 patients underwent surgery and one patient performed chemoradiotherapy because of patient refusal. cT3 was 85%, cStage III and IV were 90%. Far advanced cases were in this study. Surgical complication was not increased compared to the historical data. R0 resection rate was achieved in 85%. The clinical response rate was 76%. Pathological response rate was 33%, which was the primary endpoint. 2-year recurrence-free survival rate was 56% and 2-year overall survival rate was 71%. The rate of Grade 3 or 4 Neutropenia was 69%, and FN was 18%. NAC-DCS was high toxic regimen, but manageable regimen. The median time of onset with Grade 3/4 neutropenia was day 11 from start of each cycle. Conclusions: NAC with DCS regimen was feasible and good response for advanced ESCC and became to a promising candidate. Further, the survival benefit of triplet regimen including S-1 should be verified by the randomized controlled trial. Clinical trial information: UMIN000017153.
Apatinib combined with SOX neoadjuvant therapy for locally advanced gastric cancer: A multicenter, single-armed, prospective study.
Authors: Lin Jian-Xian , Huang Changming
Published: February 2020

367

Background: Molecular targeted therapy has made great progress in the treatment of gastric cancer. In some previous studies, apatinib, an oral small molecular of VEGFR-2 TKI, had been confirmed can improve OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. However, there is limited evidence about the safety and feasibility of apatinib combined with SOX regimen as neoadjuvant therapy for locally advanced gastric cancer (AGC). Methods: This is a multicenter, single-armed, prospective study. Patients with AGC (cT2-4N+M0) without prior anti-cancer strategies were included. Patients were received 2 to 5 cycles (21 days a cycle) of neoadjuvant therapy using S-1 (po, 40-60 mg bid, day1-day14), oxaliplatin (iv, 130 mg/m2, day1), and apatinib (po, 500 mg qd). Apatinib was prohibited in the last cycle. The operation should be performed 2 to 4 weeks later of the neoadjuvant therapy. The primary endpoint was R0 resection rate. The secondary endpoint included safety, ORR, and DCR. Results: A total of 56 patients from 10 centers in China were recruited. There were 43 males and 13 females. The median age was 63.04 years (range 41-75 years). There were 43 patients with tumor response evaluation, 29 patients (67.4%) had partial response (PR), 12 patients (27.9%) had stable disease (SD), and 2 patient (4.6%) had progressive disease (PD). The ORR and DCR were 67.4% (29/43) and 95.3% (41/43), respectively. 36 patients received gastric surgery, the R0 resection rate was 97.2%, 3 patients had postoperative complication: one had intestinal obstruction and 2 had pneumonia (all Clavien-Dindo classification less than grade II). 46 patients were included for safety analysis. The incidence of adverse events (AEs) and grade 3/4 AEs were 84.8% (39/46) and 17.4% (8/46), respectively. The most common AEs were neutropenia (40%), low platelet count (40%), leucopenia (32.6%), vomit (13%). Conclusions: This prospective study shows that neoadjuvant therapy using apatinib plus SOX brings clinical benefit to AGC with a high disease control rate and tolerable adverse reactions. Clinical trial information: NCT 03192735.
Short- and long-term outcomes following laparoscopic gastrectomy for advanced gastric cancer compared with open gastrectomy.
Authors: Shibuya Kazuaki , Kawamura Hideki , Ohno Yosuke , Ichikawa Nobuki , Yoshida Tadashi , Homma Shigenori , Taketomi Akinobu
Published: February 2020

369

Background: To investigate the oncological feasibility and technical safety of laparoscopic gastrectomy with D2 lymphadenectomy for advanced gastric cancer. Methods: 186 advanced gastric cancer patients treated by gastrectomy with D2 lymphadenectomy were eligible for inclusion including those with invasion into the muscularis propria, subserosa, and serosa without involvement of other organs, and stages N0–2 and M0. We retrospectively compared the short- and-long term outcomes between laparoscopic gastrectomy and open gastrectomy. Results: We analyzed short-term outcomes by comparing distal- with total gastrectomy results. We found no significant difference for distal gastrectomy for postoperative morbidity (laparoscopic vs. open: n = 4 (4.6%) vs. n = 1 (3.6%); p= 1.00). We also found no significant difference in postoperative morbidity for total gastrectomy (laparoscopic vs. open: n = 2 (4.0%) vs. n = 1 (4.0%); p= 1.00). No deaths occurred in any group. The entire cohort analysis revealed no statistically significant differences in overall- or recurrence-free survival between the laparoscopic and open groups. For overall survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III ( p= 0.29 and 0.27, respectively), and for pathological stage II or III ( p= 0.88 and 0.86, respectively). For recurrence-free survival, there were no significant differences between open and laparoscopic groups for clinical stage II or III ( p= 0.63 and 0.60, respectively), and for pathological stage II or III (p = 0.98 and 0.72, respectively). Conclusions: Laparscopic gastrectomy for advanced gastric cancer compared favorably with open gastrectomy regarding short- and long-term outcomes. Clinical trial information: 160907.
A novel preoperative risk score to optimize patient selection for performing concomitant liver resection with cytoreductive surgery/HIPEC.
Authors: Lee Rachel M. , Gamboa Adriana C. , Turgeon Michael K. , Grotz Travis Edward , Fournier Keith F. , Dineen Sean Patrick , Veerapong Jula , Clarke Callisia , Patel Sameer H. , Henrix Ryan James , Lambert Laura A. , Abbott Daniel Erik , Raoof Mustafa , Johnston Fabian McCartney , Staley Charles A. , Cloyd Jordan , Maithel Shishir K. , Russell Maria C.
Published: February 2020

37

Background: While parenchymal hepatic metastases were previously considered a contraindication to cytoreductive surgery(CRS) and heated intraperitoneal chemotherapy(HIPEC), liver resection(LR) is increasingly performed concomitantly with CRS/HIPEC. As this practice continues to expand, identification of preoperative factors associated with poor outcomes is paramount. Methods: Patients from the US HIPEC Collaborative(2000-2017) with invasive appendiceal or colorectal adenocarcinoma undergoing primary, curative intent CRS/HIPEC with CC0-1 resection were included. LR was defined as a formal parenchymal resection. Primary endpoints were postoperative complications and overall survival(OS). Results: 658 patients were included. Average age was 54 years and 45% were male; 83 (15%) underwent liver resection of colorectal (58%) or invasive appendiceal (42%) metastases. Liver resection patients had more complications (81 vs 60%; p = 0.001), greater number of complications (2.3 vs 1.5; p < 0.001), and required more reoperations (22 vs 11%; p = 0.007) and readmissions (39 vs 25%; p = 0.014) than non-liver resection patients. Liver resection patients had decreased OS (2-year OS 62% vs 79%, p < 0.001), which persisted on multivariable Cox regression when accounting for PCI and histology type. Preoperative factors associated with decreased OS on multivariable analysis in patients undergoing liver resection included age < 60 years (HR:3.61), colorectal histology (HR:3.84), and multiple liver tumors (HR:3.45) (all p < 0.05). When assigning one point for each factor, there was an incremental decrease in 2-yr survival as the risk score increased from 0 to 3 (0: 100%; 1: 91%; 2: 58%; 3: 0%; p < 0.001). Conclusions: As concurrent liver resection with CRS/HIPEC has become more common, we created a simple risk score to stratify patients considered for CRS/HIPEC with liver resection. These data aid in striking the balance between an increased perioperative complication profile with the potential for improvement in overall survival.
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.

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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.