bluuebunny/crossref_metadata_2025 huggingface dataset:
Is three years duration of adjuvant imatinib mesylate treatment sufficient for patients with high-risk gastrointestinal stromal tumor? A study based on long-term follow-up.
Authors: Lin JianXian
Published: March 2017

130

Background: The therapy for gastrointestinal stromal tumors (GIST) has changed significantly since the use of Imatinib Mesylate (IM). However, the appropriate duration of receiving adjuvant IM for patients with high-risk GIST who underwent R0 resection is still controversial. Methods: From Jan. 2005 to Dec. 2014, 234 patients who underwent R0 resection and were treated with adjuvant IM were identified from a database. The effect of the medication duration on the long-term outcomes was analyzed. Results: In this study, the 5 year recurrence-free survival (RFS) rate and overall survival (OS) rate in the whole groups were 76.2% and 83.4%, respectively. The patient's prognosis was improved due to the prolongation of the time of receiving the Imatinib treatment (P < 0.05). According to the risk stratification analysis, the survival of the moderate-risk patients who received IM adjuvant therapy for 1 year, 1-3 years and more than 3 years showed improved, but the difference was not statistically significant (P > 0.05). However, in the high-risk patients, the RFS rates of the 1 year group, 1-3 years group, 3-5 years group and more than 5 years group were 36.5%, 68.7%, 71.2% and 90.8%, respectively, and the OS rates were 36.7%,76.6%, 84.0% and 97.4%, respectively (P < 0.001). Additionally, linear regression analysis showed that the long-term outcomes of patients with high-risk GIST significantly improved due to prolonged adjuvant IM treatment durations (P < 0.05). The RFS rate of patients receiving IM more than 5 years was significantly better than those receiving it for less than 5 years. Multivariate analysis in the patients with high-risk GIST showed that tumor located in small intestine was an independent risk factor, while receiving IM treatment was an independent protective factor for prognosis. Conclusions: The long-term outcomes of patients with high risk GIST improved due to the prolongation of the IM treatment. To reduce the recurrence and improve the long-term survival, we suggest that patients with high-risk GIST receive Imatinib treatment for at least 5 years.
Impact of squamous histology on the response to treatment and long-term outcomes of patients with distal esophageal cancer.
Authors: Shah Parth Kishore , Cameron Miles , Frakes Jessica M. , Fontaine Jacques , Coppola Domenico , Hoffe Sarah E. , Almhanna Khaldoun , Pimiento Jose Mario
Published: March 2017

135

Background: Squamous cell carcinoma (SCC) has been traditionally linked to a better response to treatment and overall survival when compared to adenocarcinoma (AC) of the esophagus. Recent advances in staging, neoadjuvant therapy (NAT) and increasing surgical management of patients with EC have led to improved overall survival of these patients. The aim of this study is to analyze the impact of squamous histology on treatment response and long term outcomes in patients with distal EC. Methods: A retrospective review of patients who underwent esophagectomy for EC at a single institution over a 16 year period (1999-2015) was performed. Pre-operative clinical parameters, stage as well as oncologic management were compared between SCC and AC of the distal esophagus and the difference in response to treatment and overall survival were analyzed using descriptive statistics. Results: Esophagectomy was performed on 945 patients with EC of which 839 patients (89%) had distal EC. The mean age of this group was 63 years and majority were male (87%). Histology was SCC for 78 patients (9.4%) and AC for 747 patients (90.6%). Pretreatment clinical stage was similar between groups (p = 0.16). NAT administration was similar between groups (p = 0.13). Although SCC patients had higher rate of complete response (54% v/s 36%, p = 0.01) we found no difference in the overall survival after surgery (33 months for SCC v/s 40 months for AC, p = 0.72) irrespective of whether they received NAT (p = 0.95) or not (p = 0.55). Conclusions: Squamous cell histology had a favorable impact on the rate of pathologic response for patients with distal EC; however, this improvement did not alter their overall survival. This could provide an insight into the decreasing significance of the histology in the management and expectations from treatment of EC while emphasizing the continuing need for multimodality therapy to assure good outcomes on these patients.
Treatment trends in gastroesophageal and gastric cancers in the United States.
Authors: Mokdad Ali , Ali Amna , Nassour Ibrahim , Mansour John C. , Wang Sam C. , Porembka Matthew R.
Published: March 2017

136

Background: Randomized clinical trials reported in the last decade have helped define gastroesophageal junction (GEJ) and gastric cancer (GC) treatment. It is unclear, however, how practice patterns have evolved following these trials. This study explores the trends in treatment of GEJ and GC over the past decade in the United States. Methods: Patients with adenocarcinoma of the stomach and distal esophagus were identified in the National Cancer Database between 2006 and 2013. Tumor located in the distal esophagus and gastric cardia was denoted GEJ. Tumors distal to the cardia constituted GC. Tumors were categorized as early (Stage IA), locally advanced (IB-IIIC), and metastatic (IV). Detailed treatment was compared according to tumor stage and location. A time trend analysis was conducted. Results: A total of 120,729 patients (GEJ: 79,654 [66%], GC: 41,075 [34%]) were identified. Stage was similar in both groups (early: 12%, locally advanced: 55%, and metastatic: 33%). Overall, 73% of early GEJ and 74% of early GC underwent resection; of those, 43% and 12% were local excisions, respectively. Local excisions increased over time in both groups (annual odds ratio [OR] = 1.2; P < 0.01). In locally advanced GEJ, neoadjuvant chemoradiotherapy (CRT) increased among patients that received multimodality treatment (53% in 2006 to 73% in 2013; OR = 1.1, P < 0.01). In locally advanced GC, the use of neoadjuvant chemotherapy (CT) increased (5% to 20%; OR = 1.2, P < 0.01) as did perioperative CT (1% to 9%; OR = 1.3, P < 0.01) in lieu of adjuvant CRT (68% to 43%; OR = 0.9, P < 0.01). Multimodality treatment use remained stable over the study period in both groups (GEJ: 42%, GC: 47%). Among patients with metastatic disease, only 61% of GEJ and 40% of GC patients received CT, with 32% and 40%, respectively, not receiving any therapy at all. Conclusions: Practice patterns for GEJ and GC changed in the last decade with increasing adoption of neoadjuvant therapy in locally advanced disease and local excision of early stage cancers. Treatment for metastatic disease remains markedly underutilized, particularly GC.
A National Cancer Database analysis of treatment utilization and associated outcomes in elderly patients with locally advanced esophageal cancer.
Authors: Vlacich Gregory Riccardo , Samson Pamela Parker , Perkins Stephanie Mabry , Roach Michael Charles , Parikh Parag J. , Bradley Jeffrey D. , Lockhart Albert C. , Puri Varun , Meyers Bryan F , Kozower Benjamin D. , Robinson Cliff Grant
Published: March 2017

138

Background: Elderly patients with locally advanced esophageal cancer pose a therapeutic challenge since definitive treatment involves aggressive combined-modality therapy. Whether these individuals are offered or benefit from these approaches in the modern, trimodality era has not been widely explored. Methods: Patients ≥ 70 years old with clinical stage II and III esophageal cancer diagnosed between 1998 and 2012 were identified from the National Cancer Database and stratified based on treatment. Variables independently associated with treatment utilization were evaluated using logistic regression and mortality hazard evaluated using Cox-proportional hazards analysis. The primary aim was to compare overall survival by treatment group. The secondary aim was to identify variables associated with receiving each modality. Results: A total of 21,593 patients were identified. Median and maximum ages were 77 and 90 respectively. In 12.9%, no therapy was delivered, 24.3% received palliative therapy, 37.1% received definitive chemoradiation, 5.6% received esophagectomy alone, and 10.0% received trimodality therapy. On multivariate analysis, age ≥ 80 (OR 0.73, p < 0.001), female gender (OR 0.81, p < 0.001), and treatment at high-volume centers (OR 0.83, p = 0.008) were associated with a decreased likelihood of palliative therapy over no treatment. Age ≥ 80 (OR 0.15, p < 0.001), female gender (OR 0.80, p = 0.03), and non-Caucasian race (OR 0.63, p < 0.001) were associated with decreased trimodality use compared to definitive chemoradiation. Each treatment independently demonstrated improved survival compared to no therapy: palliative treatment (HR 0.49), concurrent chemoradiation (HR 0.36), esophagectomy (HR 0.31), trimodality therapy (HR 0.25), all p < 0.001. Conclusions: Any therapy, including palliative care, was associated with improved survival compared to no treatment in elderly patients with esophageal cancer. Subsets of patients are less likely to receive aggressive therapy based on social and institutional factors. Care should be taken to not unnecessarily deprive elderly patients of treatment that may improve survival.
Comparison between local and extended field radiotherapy, including regional nodes radiotherapy, in combination with concurrent chemotherapy for T1bN0M0 esophageal cancer.
Authors: Nakatani Yukihiro , Kato Ken , Shoji Hirokazu , Iwasa Satoru , Honma Yoshitaka , Takashima Atsuo , Hamaguchi Tetsuya , Ito Yoshinori , Itami Jun , Saito Yutaka , Boku Narikazu , Umezawa Rei
Published: March 2017

142

Background: Extended field (EF) radiotherapy including regional nodes, has been adopted for the treatment of esophageal squamous cell carcinoma (ESCC), but it sometimes causes severe radiation-related adverse events. The purpose of this study is to compare local-field (LF) to EF radiotherapy administered as chemoradiotherapy (CRT) in early esophageal cancer. Methods: Selection criteria included histologically proven T1bN0M0 ESCC, performance status (PS) 0-1, adequate organ function and no other active malignancy. Data on patients who received CRT concurrently with 5-FU and cisplatin between Jan. 2000 and Dec. 2012 in our hospital were evaluated. All patients received radiotherapy at a dose of 60Gy without a planned break. The clinical target volume (CTV) of LF included gross tumor volume (GTV) plus 3-cm superior and inferior margins, and that of EF included GTV plus regional lymph nodes. Overall survivals (OS) were estimated with the Kaplan-Meier method and compared with the log-rank test. The Cox regression model was used for multivariate analysis. Adverse events were graded according to the CTCAE v.4.0. Results: The characteristics of the EF group (n = 120) and LF group (n = 79) are: Median age, 68.0 years and 65.0 years; male/female, 106/14 and 67/12; PS 0/1, 93/27 and 63/18; median tumor length, 40.6mm and 35.4mm, respectively. The complete response rates were 90.0% and 98.7%, respectively. The median follow-up periods were 103 months and 69 months, respectively. The 5-year overall and cause-specific survival rates were 74.5% and 90.6%, 89.5% and 91.8%, respectively. According to a multivariate analysis, EF was a significant negative prognostic factor for OS (hazard ratio = 2.88, p = 0.002) but not for cause-specific survival. Cardiopulmonary toxicities of grade 3 or greater were observed more frequently in the EF group (p = 0.035), with statistical significance. Treatment-related death occurred at 6.7% and 1.3%, respectively, in the two groups. Conclusions: It is suggested that radiation with LF may be better than EF in combination with concurrent chemotherapy in early esophageal cancer (T1bN0M0).
Outcomes of locoregional therapy for metastatic gastric cancer.
Authors: Shridhar Ravi , Huston Jamie , Meredith Kenneth L
Published: March 2017

143

Background: Patients with metastatic gastric cancer have poor survival. The purpose of this study was to compare outcomes of metastatic gastric cancer patients with or without surgery and radiation therapy (RT). Methods: The National Cancer Database (NCDB) was accessed to identify patients with stage IV gastric cancer between 2004 and 2013 and stratified by surgery. Propensity score matching was performed against age, metastatic site, radiation, and signet ring histology. Overall survival (OS) analysis was determined by Kaplan-Meier and log-rank analysis. Multivariate analysis (MVA) was analyzed by the Cox proportional hazard ratio model. Results: A total of 1808 patients were identified. Surgery was associated with an OS benefit. Median and 5-year OS for surgery and no surgery was 16 months and 16% and 10 months and 2%, respectively (p < 0.001). Median and 5 year OS for patients treated with surgery and RT was 22.4 months and 26%. Median and 5 year OS for surgery patients treated with or without preoperative RT was 27.2 months and 28% and 15.2 months and 12%, respectively (p < 0.001). There was no OS benefit with postoperative RT. MVA for all patients revealed that surgery and tumor location were associated with decreased mortality while peritoneal metastases were associated with increased mortality. In surgical patients, MVA showed that RT, partial esophagectomy, and tumor location were associated with decreased mortality, while positive margins, signet ring histology, and peritoneal metastases were associated with increased mortality. In nonsurgical patients, only carcinomatosis was prognostic on MVA. Conclusions: Surgery and radiation are associated with increased survival in a subset of patients with metastatic gastric cancer. Prospective trials will be needed to address the role and sequence of surgery and radiation in metastatic gastric cancer.
Comparison of long-term outcomes of endoscopic submucosal dissection and surgery for esophagogastric junction adenocarcinoma.
Authors: Kim Do Hoon , Gong Eun Jeong , Ahn Ji Yong , Jung Kee Wook , Lee Jeong Hoon , Choi Kee Don , Song Ho June , Lee Gin Hyug , Jung Hwoon-Yong , Lee In-Seob , Kim Beom Su , Yoo Moon-Won , Oh Sung Tae , Yook Jeong Hwan , Kim Byung Sik
Published: March 2017

144

Background: Endoscopic submucosal dissection (ESD) has been accepted as standard treatment for early gastric cancer. However, comparative outcomes of ESD and surgery have not been evaluated for adenocarcinoma in the esophagogastric junction (EGJ). We investigated the long-term outcomes of ESD compared with surgery for adenocarcinoma in the EGJ. Methods: Subjects who underwent ESD or surgery for Siewert type II adenocarcinoma which met absolute and expanded criteria between 2005 and 2010 were eligible for this study. Clinical features and treatment outcomes were retrospectively reviewed using medical records. Results: Among 79 patients included, 40 underwent ESD and 39 underwent surgery. During the median follow-up period of 60.9 months (range: 13.1-125.4 months), the 5-year overall survival rates were 93.9% and 97.3% for ESD and surgery groups, respectively ( p= 0.376). There was no gastric cancer-related deaths in either groups. Adverse events occurred in 11 patients (13.9%) overall and the incidence of treatment-related adverse events was similar between two groups (10.0% vs. 17.9%, p= 0.308). Conclusions: ESD may be an effective alternative to surgery for the treatment of early gastric cancer in the EGJ, based on comparable long-term outcomes.
Patterns of treatment and outcomes in elderly patients with non-metastatic, unresected gastric adenocarcinoma: A review of the Florida cancer data system.
Authors: Vlacich Gregory Riccardo , Samson Pamela Parker , Stowe Hayley , Hsieh Samantha , Robinson Cliff Grant , Perkins Stephanie Mabry
Published: March 2017

146

Background: Concurrent chemoradiation is considered definitive treatment for unresected, localized gastric adenocarcinoma, but utilization in the elderly is complicated by increased toxicity risk and limited life expectancy. The benefit of concurrent chemoradiation in this population over non-definitive therapy is not well characterized. Methods: The Florida Cancer Data System was queried for patients ≥ 60 years old diagnosed with non-metastatic gastric adenocarcinoma between 2004 and 2010 who did not undergo primary surgery. Logistic regression was performed to evaluate variables independently associated with treatment and mortality hazard was evaluated using Cox-proportional modeling. The primary aim was to compare overall survival between groups. Results: A total of 1,729 patients were identified with a median and maximum age of 79 and 101 years respectively. The majority received no therapy (68.4%) followed by concurrent chemoradiation (12.0%), chemotherapy alone (10.5%), radiation alone (5.0%), and sequential chemoradiation (4.2%). Median survival with no treatment was 3.7 months (95% CI: 3.3-4.1) and no difference was seen with radiation alone (MS 5.4 months, p = 0.85). However, improved survival was seen with chemotherapy alone (9.1 months), and concurrent (10.5 months) and sequential (12.5 months) chemoradiation, all p < 0.001 compared to no therapy. Despite a modest survival benefit with sequential chemoradiation compared to chemotherapy alone (p = 0.046), this was not seen with concurrent chemoradiation (p = 0.215) or between concurrent and sequential chemoradiation (p = 0.266). On multivariate analysis, age ≥ 80 (OR 0.41, p < 0.001) and African-America race (OR 0.45, p = 0.004) were independently associated with no treatment compared to receiving any chemotherapy. Conclusions: Chemotherapy may improve survival over those not receiving systemic therapy, and the addition of radiation does not appear to provide any added benefit over chemotherapy alone. Advanced age and African-American race are strong predictors against chemotherapy use, however additional factors not accounted for such as performance status may contribute.
Trends in multimodality therapy for gastric cancer post-MAGIC.
Authors: Sada Yvonne , Smaglo Brandon George , Tran Cao Hop Sanderson , Akce Mehmet , Mok Henry , Musher Benjamin Leon , Massarweh Nader Nabile
Published: March 2017

148

Background: Althoughmultimodality therapy (MMT) is recommended for most patients with resectable gastric cancer, no single approach has been established as standard. As such, little is known about current national practice patterns and MMT treatment sequencing for patients with gastric cancer. Methods: This was a retrospective cohort study of ≥ T2 and/or node positive gastric cancer patients treated with MMT using the National Cancer Database (2006-2012). Patients were categorized based on type of MMT (chemotherapy, concurrent chemoradiation (cXRT), or both chemotherapy and cXRT) and treatment sequence (preoperative, postoperative, or perioperative). Accuracy of pre-treatment clinical nodal staging was ascertained by comparison to pathologic nodal staging in patients treated with upfront surgery. Multivariable Cox regression was used to evaluate the association between overall risk of death and MMT type and sequence. Results: Among 4,857 patients, 14.1% were treated perioperatively, 48.0% preoperatively, and 37.9% postoperatively. Rates of chemotherapy, cXRT, and both chemotherapy and cXRT were 32.1%, 53.4%, and 14.5%. Among patients treated with upfront surgery, sensitivity, specificity, PPV, and NPV of clinical nodal staging were 70.7%, 88.8%, 92.1%, and 62.2%, respectively. Over the study period, use of cXRT decreased (61.8% 2006 vs 52.0% 2012; trend test, p < 0.001) while use of chemotherapy increased (23.6% vs 35.7%; trend test, p < 0.001) and use of both chemotherapy and cXRT did not change. There was an increase in the use of perioperative treatment (8.1% vs 17.4%; trend test, p < 0.001) while postoperative treatment decreased (44.4% vs 31.1%; trend test, p < 0.001). After multivariable modeling, neither type of MMT nor treatment sequence was associated with risk of death. Conclusions: Although current national practice patterns favor pre- and perioperative treatment, one third of patients were treated with upfront surgery. Survival was not associated with MMT type or sequence. However, given the high false negative rate of clinical nodal staging and high non-completion rate of postoperative treatment (50% in MAGIC trial), efforts to improve gastric cancer outcomes should focus on increasing use of preoperative therapy.
Phase II study of trastuzumab with irinotecan in HER2-positive metastatic or advanced gastric cancer patients previously treated with trastuzumab and failed: HGCSG 1201/OGSG1205.
Authors: Kawamoto Yasuyuki , Meguro Takashi , Yuki Satoshi , Nakatsumi Hiroshi , Sasaki Takahide , Hatanaka Kazuteru , Uebayashi Minoru , Iwanaga Ichiro , Abe Nobuhiko , Nakamura Michio , Okuda Hiroyuki , Eto Kazunori , Oba Ayane , Abe Masakazu , Oba Koji , Satoh Taroh , Sakata Yuh , Sakamoto Naoya , Komatsu Yoshito ,   Hokkaido Gastrointestinal Cancer Study Group
Published: March 2017

151

Background: Some phase II and III studies of second-line chemotherapy for metastatic or advanced gastric cancer have been reported in recent years. Irinotecan is one of the standard regimen for second-line therapy. On the other hand, the efficacy of continuing trastuzumab (Tmab) beyond progression in patients (pts) who had previously been treated with Tmab plus standard first line chemotherapy has not been reported. We conducted this study to assess the efficacy and safety of Tmab with irinotecan in HER2-positive gastric cancer pts previously treated with Tmab (UMIN ID: 000007636). Methods: Patients with HER2-positive metastatic or advanced gastric cancer who were previously treated with Tmab and failed were included. Pts received Tmab every 3 weeks and irinotecan every 2 weeks. Primary endpoint was response rate (RR), and secondary endpoints were progression-free survival (PFS), six-month survival rate, safety, sub-group analysis by HER2 status (IHC 3+ group, IHC 2+/FISH positive group), and so on. Results: Only 16 pts were enrolled from 9 institutions in three years during a pre-planned registration period. We stopped this study on the way, unfortunately. In a total of 16 pts, one patient was excluded and 15 were analyzed. Median age was 65, male/female; 9/6, ECOG PS 0/1; 8/7, and IHC 3+/IHC 2+ and FISH positive; 10/5, respectively. Response rate was 7% and disease control rate was 53%. Median PFS and overall survival (OS) were 2.4 (95%C.I.; 0.0-5.2 months) and 9.7 months (95%C.I.; 8.2-11.2 months), respectively. Six-month PFS rate was 13%. In sub-group analysis by HER2 status, median PFS of IHC 3+ and IHC 2+/FISH positive were 2.2 and 2.4 months, respectively. Median OS of each groups were 8.8 and 10.8 months. The most frequently reported grade 3-4 adverse events were neutropenia (40%), anemia (27%), anorexia (33%), and fatigue (33%). Conclusions: This study was closed prematurely due to poor accrual. It seemed that continued use of Tmab and irinotecan beyond disease progression has not significant clinical benefit in HER2-positive metastatic or advanced gastric cancer pts previously treated with Tmab. Clinical trial information: UMIN000007636.
Efficacy and safety of taxane-monotherapy in advanced gastric cancer refractory to triplet chemotherapy with docetaxel, cisplatin, and S-1: A multicenter retrospective study.
Authors: Kawai Sadayuki , Iizumi Sakura , Takashima Atsuo , Narita Yukiya , Tajika Masahiro , Matsushima Tomohiro , Yasui Hirofumi , Muro Kei , Takahari Daisuke , Boku Narikazu
Published: March 2017

154

Background: While taxane-monotherapy following fluoropyrimidine plus platinum is recognized as the standard treatment strategy for advanced gastric cancer, triplet chemotherapy with docetaxel, cisplatin and S-1 (DCS) is another option for first-line therapy in Japan. However, efficacy of taxane after DCS therapy has not been sufficiently evaluated. Methods: We retrospectively evaluated the efficacy and safety of taxane-monotherapy after DCS between January 2010 and April 2015 for advanced gastric cancer. The taxane-monotherapy included weekly paclitaxel (PTX) (80 mg/m2, day 1, 8 and 15 of a 28-day cycle) and triweekly nab-PTX (260 mg/m2, day 1). Other selection criteria were: ECOG PS < 2; adequate organ function; no severe ascites; HER2-negative. Results: Thirty of 92 patients who had been treated with DCS received taxane-monotherapy. Fifteen and 15 patients received taxane-monotherapy as the second and third-line treatment, respectively. Patients characteristics of each group (2nd/3rd) were; median age: 64/62 (range 27-75/42-75); ECOG PS ≤ 1: 14/13; number of metastatic sites ≥ 2: 9/12; median taxane-free interval from first-line treatment: 1.6/3.4 (range 0.9-2.3/2.2-8.3) months; median total dose of prior DTX: 349/208 (range 39-844/141-685) mg/m2. Number of patients who received PTX/nab-PTX were 10/5 and 13/2 in the second and third line treatment. Median relative dose intensity of taxane was 96.4% (range 57.6-172.9%) in the second-line, 98.5% (44.0-166.8%) in the third-line group. Response rate and disease control rate were 0% and 37.5% in the second-line, and 0% and 38.5% in the third-line group. Median progression free survival and overall survival were 3.4 and 5.8 months in the second-line group, and 2.0 and 4.5 months in the third-line. Grade 3 or 4 neutropenia, anemia, and anorexia, occurred in 33%, 13% and 13% in the second-line group, and 6.7%, 13% and 6.7% in the third–line group, associated with no treatment related death. Conclusions: It is suggested that taxane-monotherapy has acceptable toxicities but insufficient efficacy in advanced gastric cancer patients after DCS therapy.
The prognostic factors for advanced gastric cancer with para-aortic nodal involvement after extended gastrectomy.
Authors: Kaito Akio , Kinoshita Takahiro , Sunagawa Hideki , Sugita Shizuki , Watanabe Masahiro , Terada Mitsumi
Published: March 2017

158

Background: The prognosis of patients with advanced gastric cancer with para-aortic lymph node (PAN) involvement is poor. We retrospectively investigated the prognostic factors for advanced gastric cancer with PAN involvement. Methods: The patients who underwent radical gastrectomy with PAN dissection for advanced gastric cancer between 1992 and 2014 in our institution included in this study. The clinicopathological features and prognostic factors of the patients who identified pathologically PAN involvement after curative gastrectomy were analyzed. Results: In this period, a total of 704 patients underwent gastrectomy with PAN dissection and 65 patients were identified as pathologically PAN positive and eligible for this study. Total gastrectomy and combined resection of other organs were performed for 48 patients and 51 patients, respectively. Complete PAN dissection (a2/b1) was performed for 32 patients. Postoperative abdominal complication was 20% with no hospital deaths. The 3 year and the 5 year overall survival (OS) were 33.8% and 21.2%, respectively. Multivariate cox regression analysis revealed nodal involvement (any of the station No.8a, No.9 and No.11; hazard ratio, 4.04; 95% confidence interval, 1.55-10.5), tumor diameter (over 120mm; HR, 3.37; 95%CI, 1.18-9.63) and total number of PAN involvement (over 2 nodes; HR, 2.24; 95%CI, 1.21-4.15) were poor prognostic factor. The patients without these poor prognostic factors had survived significantly longer than the patient with any of these factors in Kaplan-meier analysis (the 5 year OS: 87.5% vs 9.4%, P <0.001). Conclusions: Tumor size, nodal involvement of the station No.8a, No.9 and No.11 and total number of PAN involvement were poor prognostic factors for advanced gastric cancer with PAN involvement. The candidates for extensive nodal dissection for advanced gastric cancer should carefully be selected.
Association of UGT1A1 gene polymorphism with the safety and efficacy of irinotecan monotherapy for advanced gastric cancer.
Authors: Yamaguchi Toshifumi , Iwasa Satoru , Shoji Hirokazu , Honma Yoshitaka , Takashima Atsuo , Kato Ken , Hamaguchi Tetsuya , Boku Narikazu
Published: March 2017

16

Background: The uridine diphosphate glucuronosyltransferase (UGT) 1A1, which transforms SN-38 into SN-38 glucuronide, is a key enzyme involved in the metabolism of irinotecan. Previous studies showed that UGT1A1 genotype is related to the toxicity of irinotecan-based chemotherapy in metastatic colorectal cancer. The purpose of this study was to investigate the relationship between UGT1A1genotype and safety and efficacy of irinotecan monotherapy in patients with advanced gastric cancer. Methods: We reviewed the data of 208 patients who were tested for UGT1A1 genotype and treated with irinotecan-based chemotherapy for advanced gastric cancer from 2009 to 2014. We evaluated the efficacy and safety of irinotecan monotherapy in the three groups with wild-type (WT), single heterozygosity (SH), and homozygosity/double heterozygosity (Homo-DH) classified by the genotypes for UGT1A1*28 or UGT1A1*6. Results: A total of 117 patients received irinotecan monotherapy: 40 patients in second-line, 74 in third-line, and 3 in forth-line therapy. The UGT1A1genotype was WT in 62 patients (53.0%), SH in 41 (35.0%), and Homo-DH in 14 (12.0%). Patients’ characteristics were similar among the three groups. The initial dose of irinotecan was reduced in 10 patients (16%) with the WT genotype, in 11 (27%) with SH, and in 10 (71%) with Homo-DH. Grade 3-4 neutropenia, diarrhea, and febrile neutropenia occurred in 13/22/64%, 6/5/21%, and 2/7/50% of WT/SH/Homo-DH patients. Median time to treatment failure of second-line and third-line therapies were 2.4/2.8/3.3 months and 2.4/2.3/1.3 months in WT/SH/Homo-DH patients. Median overall survival of second-line and third-line therapy were 7.9/9.9/4.6 months and 6.9/6.3/2.8 months in WT/SH/Homo-DH patients. Conclusions: Patients with UGT1A1 Homo-DH displayed high frequency of grade 3-4 toxicities, although the initial dose of irinotecan was reduced in some patients. UGT1A1 polymorphism may be related to the efficacy of irinotecan monotherapy in second- and third-line treatments for advanced gastric cancer.
Converting borderline-resectable, locally-advanced esophageal carcinoma to resectability with neoadjuvant chemoradiotherapy.
Authors: Horne Zachary D. , Sun Weijing , Gibson Michael K. , Pennathur Arjun , Luketich James D. , Karlovits Brian J , Heron Dwight Earl , Greenberger Joel S.
Published: March 2017

160

Background: Treatment of T3-4/N+ esophageal cancer is challenging. Outcomes are suboptimal and patterns of care are not well defined for borderline-resectable esophageal cancer (BREC). We present our institutional experience using preoperative chemoradiotherapy (CRT) in the management of BREC. Methods: We identified 67 patients with T3-4/N+ BREC who were treated with concurrent CRT between 2009 and 2014. Survival was calculated with Kaplan-Meier curves and cohort comparisons were made with log-rank test and Cox regression. Results: We treated 67 patients (81% males, median age 61 years, and KPS of 80), primarily with T3N2 disease. Median follow-up was 16 months. The most common CRT regimen was 58.8Gy in 28 fractions with carboplatin and paclitaxel. Median survival was 16.5 months. Forty two (62.7%) patients underwent minimally invasive Ivor-Lewis esophagectomy within 100 days of CRT. Resected patients had a median survival of 30.6 vs. 6.4 months without surgery (p<.001). Pathologic complete response and pN0 was 30.0% and 59.5%, respectively. Acute grade 3+ toxicity was seen in 34.3% and late grade 3+ toxicity in 49.3%. Three patients (4.5%) died during CRT or before surgery. Predictors of overall survival (OS) on univariate analysis included age, KPS, male gender, absence of radiographic progression and surgical resection (all p<.05). Surgery remained significant on multivariate analysis (HR 0.215 [95%CI .114-.408, p<.001]). For resected patients, survival was predicted by positive margins, pathologic N stage, and number of positive nodes (all p<.05). The only predictor of OS on multivariate analysis was pathologic N stage, with actuarial 1- and 2-year OS for pN0 vs. pN+ of 96.2%/73.1% vs 53.3%/40.0% (p=.001). pN+ patients receiving adjuvant chemotherapy (53.3%) had improved survival of 26.7 vs 8.3 months without (p=.023). Conclusions: Preoperative CRT enabled a significant proportion of patients with BREC to proceed with a potentially curative resection. Further investigation with careful patient selection is warranted in incorporating a trimodality strategy to optimize outcomes and better define a treatment algorithm for this complex cohort of patients.
Trends in utilization of chemotherapy and radiation for resectable gastric adenocarcinoma: An NCDB analysis.
Authors: Motz Benjamin Mitchell , Lorimer Patrick Daniel , Walsh Kendall K , Perry I'sis N , Han Yimei , White Richard L. , Salo Jonathan C. , Hill Joshua S.
Published: March 2017

163

Background: Locally advanced gastric adenocarcinoma (GACa) is optimally treated with a combination of surgery, chemotherapy (CHEMO) and radiation (RT). Utilization of therapies can vary with institutional practices. Methods: The NCDB was queried for pts with GACa who had RO resection (2006-2012). Pts with metastatic disease, incomplete pathologic staging, and incomplete CHEMO or RT sequencing data were excluded. Pts were divided into groups by treatment regimen: G1: perioperative CHEMO; G2: adjuvant CHEMO±RT; G3: neoadjuvant CHEMORT; G4: other adjunctive regimens; G5: surgery only. Pts who received neoadjuvant therapy were staged using clinical TNM; those who did not or had incomplete clinical staging were staged using pathologic TNM. 3 subsets were created: LOCAL: T0-2N0, LOCALLY ADV: T3-4N0, REGIONAL: N+. Chi-square, univariate, multivariable with stepwise selection, and Cochran-Armitage time trend analyses were performed. Results: N = 12946: G1 = 1099, G2 = 4771, G3 = 180, G4 = 244 and G5 = 6652. The percentage of pts receiving adjunctive therapy was determined for each subset: LOCAL = 17.2%, LOCALLY ADV = 59.8%, and REGIONAL = 66.0%. Use of adjunctive therapy increased from 2006: 44% to 2012: 53% (p < 0.01). Use of perioperative CHEMO increased from 2006: 4% to 2012: 18% (p < 0.01). Factors affecting use of adjunctive therapy on multivariable analysis are: age (p < 0.01), race (p < 0.01), income (p < 0.01), insurance (p < 0.01), comorbidity score (p < 0.01), and facility volume (p = 0.01). Conclusions: Though utilization of adjunctive therapy is increasing, a large proportion of pts with resectable GACa do not receive recommended adjunctive therapy. This study highlights disparities in utilization of optimal multimodality care. National efforts to expand access to care are necessary to improve outcomes in resectable GACa. [Table: see text]
Comparative outcomes of minimally invasive and robotic-assisted esophagectomy.
Authors: Meredith Kenneth L , Huston Jamie , Shridhar Ravi
Published: March 2017

167

Background: Minimally invasive esophagectomy(MIE) has demonstrated superior outcomes compared to open approaches. The myriad of techniques has precluded the recommendation of a standard approach. The addition of robotics has potential to further improve outcomes. We sought to compare the outcomes of existing techniques for MIE with robotic assisted approaches. Methods: Utilizing a prospective esophagectomy database we identified patients who underwent (MIE) via Ivor Lewis(TT), transhiatal(TH) or robotic assisted Ivor Lewis(RAIL) techniques. Patient demographics, tumor characteristics and complications were analyzed via ANOVA, Chi-Square, and Fisher Exact where appropriate. Results: We identified 302 patients who underwent MIE: TT 95(31.5%), TH 63(20.8%), and RAIL 144(47.7%) with a mean age of 65±9.6. The length of operation was longer in the RAIL: TT(299±87), TH(231±65), RAIL(409±104 minutes), p < 0.001. However the EBL was lower in the RAIL patients: TT(189±188ml), TH(242±380ml), RAIL(155±107ml), p = 0.03. Conversion to open was also lower in the RAIL group: TT 7(7.4%), TH 8(12.7%), RAIL 0, p < 0.001. The R0 resection rate and lymph node (LN) harvest also favored the RAIL cohort :TT 86(93.5%), TH 60(96.8%), and RAIL 144(100%), p = 0.01. LN:TT 14±7, TH 9±6, and RAIL 20±9, p < 0.001. The overall morbidity was lower in RAIL patients: TT 29(30.5%), TH 39(61.9%), RAIL 34(23.6%), p < 0.001. Mortality was lower in the TT and RAIL approaches compared to TH but was not significant: TT 2 (2.1%), TH 2 (3.2%), and RAIL 2 (1.4%), p = 0.6. Conclusions: RAIL demonstrates lower EBL, conversion to open, and morbidity than other MIE techniques. Additionally the oncologic outcomes measured by R0 resections and LN harvest also favored the patients who underwent RAIL.
Role of surgery for gastric cancer with liver limited multiple metastases.
Authors: Shirasu Hiromichi , Tsushima Takahiro , Tanizawa Yutaka , Hamauchi Satoshi , Todaka Akiko , Yokota Tomoya , Machida Nozomu , Yamazaki Kentaro , Fukutomi Akira , Terashima Masanori , Uesaka Katsuhiko , Yasui Hirofumi
Published: March 2017

170

Background: Although it has been suggested that surgery provides favorable outcome for gastric cancer (GC) patients (pts) with liver limited multiple metastases (LLM), the survival benefit of surgery comparing to systemic chemotherapy (CTx) has yet to be elucidated, especially in pts with LLM. The aim of this study was to explore the role of surgery for GC with LLM. Methods: We retrospectively reviewed the data of consecutive GC pts with LLM who underwent hepatectomy or received systemic CTx as initial therapy at Shizuoka Cancer Center between Dec. 2004 and Dec. 2015. Inclusion criteria were as follows: ECOG PS 0-1; histologically proven adenocarcinoma; synchronous or metachronous LLM; 2 or 3 LLM technically resectable disease; no prior CTx or radiotherapy Pts who were refractory to adjuvant CTx were excluded. Results: Nine of 24 pts who met the inclusion criteria underwent hepatectomy, and 15 pts received CTx. Pts’ background who received hepatectomy versus (vs) CTx was as follows: median age (range), 74 (64-81) vs 59 (42-76) years; male/female, 8/1 vs 14/1 pts; Histology intestinal/diffuse, 9/0 vs 10/5 pts; HER2 positive/negative/unknown 0/0/9 vs 2/5/8 pts; number of liver metastases 2/3, 9/0 vs 9/6; unilobar/bilobar, 5/4 vs 5/10 pts. In hepatectomy group, all 9 pts underwent radical hepatectomy (with gastrectomy for synchronous metastases), and 3 pts received adjuvant CTx. No in-hospital death or severe complication was observed. In CTx group, 11 pts received fluoropyrimidine plus cisplatin therapy, and trastuzumab was combined in 2 pts with HER2 positive tumor. Three pts underwent radical hepatectomy after CTx. Eight pts in hepatectomy group had recurrence. Recurrent sites were remnant liver (7), lymph node (1), and peritoneum (2). With median follow-up time of 47.9 months, median progression free survival was 8.0 months in hepatectomy group and 27.9 months in CTx group (p = 0.02). In CTx group, 3 pts who underwent subsequent radical hepatectomy after CTx had no recurrence or death. Median overall survival was 24.1 months in hepatectomy group and 38.4 months in CTx group (p = 0.15). Conclusions: Initial surgery for GC pts with LLM did not show survival benefit. But radical hepatectomy subsequent to CTx may associate with preferable outcome.
Clinical outcomes of elderly patients with esophageal cancer treated with chemoradiotherapy in the modern era.
Authors: Xu Cai , Xi Mian , Moreno Amy , Shraishi Yutaka , Komaki Ritsuko , Lin Steven H.
Published: March 2017

174

Background: The optimal treatment approach is not clearly defined for elderly patients with esophageal cancer. We retrospectively analyzed the clinical outcomes of elderly patients ≥ 80 years old treated at a single institution in the modern era. Methods: Patients 80 years or greater with thoracic esophageal cancer who were treated consecutively with conventional modern radiotherapy (intensity-modulated radiation therapy or proton beam therapy) and concurrent chemotherapy between 2004 and 2016 were identified and included in this study. The one patient who had surgery was excluded. Toxicity was assessed using the CTCAE v.4.0. The rates of overall survival (OS) and recurrence free survival (RFS) were calculated with the Kaplan-Meier method. A p-value less than 0.05 indicated statistical significance. Results: Of the 1617 patients, 47 patients met the eligibility criteria. The median age was 81 years (range, 80-92 years). Most patients had some comorbid illnesses, with 81%, 9%, and 11% of patients having some cardiac, pulmonary, or diabetic related diseases, respectively. Twelve of 47 patients (26%) were given induction chemotherapy. The median dose was 50.4 Gy (range, 45 Gy-50.4 Gy). The clinical complete rate was 86%. With a median follow-up of 18 months (ranges, 1.9-117.6 months), the 2-year and 5-year OS was 54.5% and 27.7%, respectively, and the 2-year RFS was 63.6%. Three patients (6.4%) developed grade 3-5 radiation pneumonitis, with 2 (4.2%) being grade 5. Eighteen patients (38%) developed grade 1 pleural effusion, and 1 was grade 3. Three patients had grade 2 arrhythmia. Six patients had grades 1-2 pericardial effusion. One patient died from myocardial infarction. Four (9%) patients developed ≥ grade 3 esophagitis, with 7 patients having grade 3 esophageal stricture. Conclusions: The treatment of esophageal cancer patients 80 years or older with concurrent chemoradiotherapy was associated with an acceptable disease outcome, but the acute and late toxicities were higher than expected, which may be due to accompanying comorbidities. More research is needed to validate our observations and to better select patients who can optimally benefit from concurrent chemoradiotherapy.
Predictive value of Surgical Apgar Score for long-term outcome in patients with gastric cancer.
Authors: Tokunaga Masanori , Irino Tomoyuki , Makuuchi Rie , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Terashima Masanori
Published: March 2017

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Background: Recently, a simple and easy complication prediction system, the surgical Apgar score (SAS) calculated according to three intraoperative parameters (estimated blood loss, lowest mean arterial pressure, and lowest heart rate), has been proposed for general surgery. We previously reported on the predictive power of SAS for severe complications after gastrectomy. However, the impact of SAS on long-term survival is still unclear. The aim of the present study was to clarify the relationship between SAS and survival outcome in patients with gastric cancer undergoing curative gastrectomy. Methods: This study included 302 patients who underwent curative gastrectomy at the Shizuoka Cancer Center in 2010. Clinical data, including intraoperative parameters, were collected retrospectively. When the SAS score was ≤ 6, patients were classified into an L-SAS group (n = 82), otherwise, they were classified into an H-SAS group (n = 220). Clinicopathological characteristics and survival outcomes were compared between the groups. Results: There was no difference in demographic data including sex and age between the groups. Total gastrectomy was more frequently performed in the L-SAS group (43%) than in the H-SAS group (21%; P < 0.001). The L-SAS group included patients with higher pT and pN stage. Five-year overall survival rate was worse in the L-SAS group (65.4%) than in the H-SAS group (82.7%; P < 0.001). Multivariate analysis, which included age, sex, histology, pT, pN, type of surgery and SAS as covariates, identified lower SAS (HR, 1.71, 95% C.I., 1.04-2.80) as well as age (HR, 1.62, 95% C.I., 1.10-2.40) and pN (HR, 2.05, 95% C.I., 1.19-3.52) as independent prognostic factors. Conclusions: The SAS was found to be a predictive factor for survival. Intraoperative bleeding and vital signs may affect survival of patients, and therefore warrant special attention from surgeons and anesthesiologists.
Laparoscopic D2 gastrectomy with complete mesogastrium excision (D2+CME) to reduce cancer leak from mesogastrium in patients with advanced gastric cancer.
Authors: Xie Daxing , Gong Jianping
Published: March 2017

18

Background: The mechanism underlying tumor recurrence following curative surgery remains unclear. It is believed that intraperitoneal free cancer cells leaked into peritoneal cavity during curative surgery play an important role. In gastric cancer, new strategies should be established towards preventing leakage of cancer cells from the primary tumor involved tissues. Our previous research demonstrated the existence of disseminated cancer cells in the mesogastrium, and we proposed laparoscopic D2 lymphadenectomy plus complete mesogastrium excision (D2+CME) as an optimized surgical procedure for advanced gastric cancer (AGC). By dissecting along the surgical planes and embryonic boundary of mesogastrium, D2+CME is repeatable with less blood lost and improved short-term surgical outcomes. In this study, we further evaluated the oncological effect of D2+CME based on the detection of “cancer leak”. Methods: The peritoneal washings were collected prior to and after tumor resection from 45 patients who underwent D2+CME (D2+CME group) and 46 patients who underwent conventional D2 lymphadenectomy (D2 group). RT-PCR was used to determine the presence of cancer cells. Positive samples are defined as those with CEA mRNA level over threshold (cutoff value). Results: Of 91 peritoneal washing samples obtained before gastrectomy, 84 (41 in D2+CME; 43 in D2 alone) showed no presence of cancer cell. After gastrectomy, CEA positive was detected in 17 of 43 (39.5%) samples with D2 group, however, only 5 of 41 (12.2%) samples in D2+CME group detected positive CEA. The average level of CEA expression in D2+CME group was also significant lower than that in D2 group after gastrectomy (p < 0.05). Presence of “cancer leak” was closely associated with pT stage and surgical procedures. The DFS of patients with CEA positive after gastrectomy was significantly poorer than that of patients with CEA negative (p < 0.05). Conclusions: LaparoscopicD2+CME could reduce the leakage of free cancer cells from the envelop of mesogastrium into the peritoneal cavity during radical gastrectomy, and thus, it might potentially increase the prognosis of AGC patients. Clinical trial information: NCT01978444.
Efficacy and safety of endoscopic submucosal dissection in elderly patients with esophageal squamous cell carcinoma.
Authors: Shin In Seub , Song Byeong Geun , Kim Doyeon , Lee Hyuk , Min Byung-Hoon , Lee Jun Haeng , Rhee Poong-Lyul , Kim Jae J. , Min Yang Won
Published: March 2017

182

Background: Endoscopic submucosal dissection (ESD) has been widely applied to superficial esophageal squamous cell carcinoma (SCC) as a minimally invasive treatment, which has advantages over surgery especially in the elderly who are at high risk of surgery. This study elucidated the efficacy and safety of ESD for superficial esophageal SCC in the elderly. Methods: Between April 2007 and June 2016, a total of 176 patients with superficial esophageal SCC were studied. The short-term outcomes including En bloc resection, complete resection, and curative resection rate and procedure-related complication rates were compared between elderly group ( n = 20, ≥ 75 years of age) and non-elderly group ( n = 156, < 75 years of age). Results: The mean age of elderly group was 76.9 ± 1.5 years and that of non-elderly group was 62.9 ± 6.9 years ( p < 0.001). Sex, past medical history (hypertension and diabetes), body mass index, tumor characteristics (number, location, shape, maximal and circumferential size of tumor and resected specimen, and depth), and presence of stricture prevention did not differ between two groups. En bloc resection (95% vs 93.6%, p > 0.999), complete resection (85% vs 73.1%, p = 0.292), and curative resection rates (75% vs 56.4%, p = 0.149) did not differ significantly between two groups. Procedure time and hospital stay were also similar. Complications of ESD such as stricture (10% vs 12.8%, p > 0.999) and perforation (10% vs 7.7%, p = 0.587) occurred similarly. Conclusions: ESD for superficial esophageal SCC is effective and safe in elderly patients like in non-elderly patients.