bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolic activity to predict clinical response and prognosis in esophageal adenocarcinoma patients treated with bimodality.
Authors: Harada Kazuto , Wu Carol C , Wang Xuemei , Mizrak Kaya Dilsa , Ghazanfari Amlashi Fatemeh , Lin Quan , Blum Murphy Mariela A. , Maru Dipen M. , Weston Brian , Lee Jeffrey H , Bhutani Manoop S. , Hofstetter Wayne Lewis , Nguyen Quynh , Ajani Jaffer A.
Published: January 2019

127

Background: Patients with localized esophageal adenocarcinoma (L-EAC) who are not suitable for surgery receive definitive chemoradiation. However, there are no biomarkers or imaging variables to predict clinical complete response (cCR; negative bx and physiologic PET post chemoradiation) or prognosticate favorable overall survival (OS). We analyzed tumor metabolic activity by standardized uptake value (SUV) or total lesion glycolysis (TLG). Methods: 266 patients with L-EAC, who declined or were unsuitable for surgery, were analyzed. Cox proportional hazards regression model for OS was analyzed using categorized SUV (low; < 6.5, moderate; 6.5-12.9, or high; ≥12.9) or TLG (low; < 24.2, moderate; 24.2-82.6, or high; ≥82.6). Logistic regression model for cCR was analyzed using categorized SUV (low; < 5.4 or high; ≥5.4) or TLG (low; < 27.0 or high; ≥27.0). Results: Mean SUV and TLG were 12.8 ± 10.7 and 209 ± 376.8, respectively. Both SUV and TLG were significantly associated with the length of the tumor (p < 0.0001) and clinical stage (p < 0.0001). Higher SUV and TLG were significantly associated with shorter OS than low SUV and TLG (moderate SUV; HR 1.79, CI 1.19-2.69, high SUV; HR 2.82, 1.90-4.18, moderate TLG; HR 1.82, 1.14-2.90, high TLG; 3.16, 2.11-4.74). 68 patients (28%) achieved cCR and remained free of recurrence. In the multivariate logistic regression model, low SUV and low TLG highly predicted cCR without recurrence (low SUV; OR 3.15, 1.38–7.19, low TLG; OR 4.79, 2.28-10.08). Conclusions: Tumor metabolic activity is highly associated with prognosis and response to chemoradiation in patients with L-EAC not undergoing surgery. Further refinements (addition of biomarkers) could allow personalized care of these patients.
Survival impact of post-progression chemotherapy (post-Cx) in advanced gastric cancer (AGC): Systematic review and meta-analysis.
Authors: Iizumi Sakura , Takashima Atsuo , Sakamaki Kentaro , Morita Satoshi , Boku Narikazu
Published: January 2019

130

Background: We conducted a systematic review and meta-analysis to assess the survival impact of post-Cx after first-line chemotherapy (1st-line Cx) and second-line chemotherapy (2nd-line Cx) for AGC. Methods: Phase III trials published in English between 2005 and 2015 or presented at annual meetings of ASCO or ESMO between 2013 and 2015 were searched. No. of patients, types of chemotherapy, and patient characteristics, proportion of post-Cx use (post-Cx%), median progression free survival (mPFS), and median overall survival (mOS) of each treatment arm were surveyed; trials not reporting these were excluded from the study. Median post-progression survival (mPPS) was calculated as difference between mOS and mPFS. Weighted Spearman's correlation coefficients between post-Cx% and survival outcomes (mOS and mPPS) were calculated. The effect of post-Cx% on survival outcomes adjusted for the types of chemotherapy and patient characteristics was evaluated by meta-regressions. Results: Overall, 25 trials were selected: 15 with 31 arms for 1st-line Cx, and 10 with 16 arms for 2nd-line Cx. Weighted Spearman's correlation coefficients between post-Cx% and mOS/mPPS were 0.520/0.739 for 1st-line Cx, and 0.767/0.823 for 2nd-line Cx, respectively. Meta-regression analysis adjusting for types of chemotherapy, age and PS, showed that 10% increase in post-Cx% was associated with prolongation of mOS by 1.033 months for 1st-line Cx and 0.34 months for 2nd-line Cx. Conclusions: Post-Cx% after 2nd-line Cx are correlated with mPPS and mOS as well as 1st-line Cx, suggesting a survival benefit of 3rd-line Cx. [Table: see text]
Redefining the learning curve for robotic esophagectomy.
Authors: Meredith Ken Lee , Huston Jamie , Briceno Pedro , Shridhar Ravi
Published: January 2019

132

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 robotic approach has increased steadily. We have previously published our series defining the learning curve for this approach. The purpose of this study is to redefine the learning curve for robotic-assisted esophagogastrectomy with respect to operative time, conversion rates, and patient safety. Methods: We have prospectively followed all patients undergoing robotic-assisted esophagogastrectomy and compared operations performed at our institutions by a single surgeon in successive cohorts. Our measures of proficiency included: operative times, conversion rates, and complications. Statistical analyses were undertaken utilizing Spearman regression analysis and Mann-Whitney U test. Significance was accepted with 95 % confidence. Results: We identified 203 patients (166 [81.8%] male: 37 [18.2%] female) of median age of 67.2 (30-90) years who underwent robotic-assisted esophagogastrectomies for malignant esophageal disease. One-hundred sixty six were adenocarcinoma, 26 were squamous cell carcinoma and 11 were other. R0 resections was performed in 202 (99.5%) of patients. The median lymph node harvest was 18 (6-63). Neoadjuvant chemoradiation was administered to 157 (77.4%) patients. A significant reduction in operative times (p <0.005) following completion of 20 procedures was identified (514 ± 106 min vs. 415± 91 min compared to subsequent 80 cases and further reduced with the subsequent 100 cases 397 ± 71.9 min) p<0.001. Complications decreased after the initial learning curve of 29 cases, p=0.04. However there was an increase in complications after 90 cases in which there was an increase in the Charleson morbidity index, p<0.01 indicating higher risk patients which tapered after case 115. Conclusions: For surgeons proficient in performing minimally-invasive esophagogastrectomies, the learning curve for a robotic-assisted procedure appears to begin near proficiency after 20 cases however as more complex cases are undertake there appears to be an additional learning curve which is surpassed after 90 cases.
Clinical characters and prognostic factors of young female patients (pts) with metastatic gastric adenocarcinoma (GC).
Authors: Cao Yanshuo , Zhang Xiaotian , Li Jian , Gong Jifang , Lu Ming , Lu Zhihao , Wang Xicheng , Zhou Jun , Li Jie , Li Yan , Shen Lin
Published: January 2019

133

Background: GC is one of the most common cancers worldwide, and has an even higher incidence rate in China. The incidence rate of GC is rising in young pts (≤ 40 years). Previous studies suggested that the percentage of female pts was higher in young pts than that in older pts. The clinical characters and potential prognostic factors have not been well described for young female pts with metastatic GC. Methods: A retrospective chart review was conducted for all GC pts treated at our institution from 1995 to 2012. Pt demographics, clinical characters, treatment related information and survival data were collected. Kaplan-Meier test was used for the survival analysis. Cox regression was conducted for uni- and multi-variate analysis. Results: In total, 1,862 pts with histologically confirmed GC were identified. Among these pts, 11.3% were young pts when first diagnosed. The male to female ratio was 2.76:1 for the whole group and 1:1.02 for young pts. Ninety-eight female pts were ≤ 40 years when diagnosed of metastatic GC. For this group, median age was 35 years (range: 19-40 years). Seventy-one (72.4%) had > 1 metastatic sites, and 85 (86.7%) received palliative chemotherapy. The median overall survival (OS) was 14.9 months (95% confidence interval [CI] 11.8-18.0 months). Seventy-six (77.6%) pts had intact primary tumor when diagnosed of metastatic disease. Compared to 22 pts who relapsed after radical surgery, OS was similar for pts presented with de novo metastatic disease (Hazard Ratio (HR) 1.03, 95% CI: 0.55 to 1.92, P= 0.9). Of these 76 pts, 36 underwent palliative gastric resection, which was associated with improved OS (15.3 vs. 9.0 months; HR 0.37, 95% CI: 0.19 to 0.74, P = 0.003). Forty-six (46.9%) pts had ovarian metastasis, and 20 had oophorectomy. Palliative oophorectomy was associated with significantly improved OS (36.6 vs. 12.4 months, HR 0.34, 95% CI: 0.14 to 0.80, P = 0.013). Conclusions: There was an increased ratio of females in young GC pts. In young female pts with metastatic GC, palliative resection of gastric primary and ovarian metastasis were associated with significantly improved OS, and should be considered in appropriate pts.
Long-term survival of gastric cancer patients with positive immunocytochemistry peritoneal washings.
Authors: Marcisz-Grzanka Katarzyna , Wieszczy Paulina , Malinowska Malgorzata , Wyrwicz Lucjan , Olesiński Tomasz
Published: January 2019

134

Background: The prognosis in gastric cancer is highly dependent on tumor stage at presentation. Surgery still remains the main therapeutic option in gastric cancer patients. However, the efficacy of this treatment may be substantially limited by the risk of peritoneal dissemination. The introduction of intraperitoneal chemotherapy (HIPEC) may affect the long-term outcomes in this group of patients, but high morbidity associated with such treatment provides the rational to identify the correct population of patients for HIPEC. Methods: This is the long-term effect analysis of prospectively observed cohort of patients assessed with immunocytochemistry peritoneal lavage in the single reffereal center. Between January 2002 and November 2004, the total of 140 patients with histologically confirmed gastric cancer were enrolled to the study. Laparotomy and intraoperative peritoneal lavage for immunocytochemistry examination were performed prior to gastrectomy. The fluid recovered was centrifuged and the sediment was fixed in 10% buffered formalin for 24 h, embedded in paraffin and cut into 4 µm-thick sections. Microscopic slides were also stained against cytokeratin 19 (CK-19), cytokeratin AE1/AE3 (CK-AE1/AE3) and mesothelioma marker. All patients were followed up with endpoints of cancer recurrence and mortality. Results: Median overall survival (OS) in patients with immunocytochemical evidence of free cancer cells in peritoneal washes was significantly shorter than in those without (11 [range: 2-55] vs. 45 [range: 1-164] months). The two groups differed significantly in long-term survival (5-year OS rate: 0.0% [0/17] vs. 43.1% [53/123]; 10-year OS rate: 0.0% [0/17] vs. 29.3% [36/123]) (p < 0.001). Positive peritoneal washing immunocytochemistry was an independent poor outcome prognostic factor after correction for all major prognostic factors. Conclusions: Positive peritoneal washing immunocytochemistry correlated with clinical staging of gastric cancer and was associated with poor overall survival (OS). With all patients dying in 5 years, this subgroup of patients defines a clear population for early salvage HIPEC for prospective verification.
Is there a role for histology based treatment choice in advanced gastric cancer (GC)?
Authors: Barile Rosalba , Squadroni Michela , Brena Federica , Cerchiaro Eleonora , Zurlo Valeria , Beretta Giordano D.
Published: January 2019

135

Background: Medical management of advanced GC is mostly dependent on prognostic assessment based on tumor stage (TNM) and clinical patients (pts)’ characteristics, other than HER2 expression. Prognostic and predictive factors are clearly needed, and histotype could be proposed as a surrogate marker of disease biology. Methods: We retrospectively analyzed pts with advanced GC treated with first line chemotherapy (CT) at Oncology Unit of Humanitas Gavazzeni (Bergamo) and Policlinico Gemelli (Roma). Pts were divided in three subgroups according to histological diagnosis: diffuse type carcinoma, intestinal type carcinoma and signet ring cell carcinoma. HER2 positive tumors were excluded from the analysis. The aim of our analysis was to compare clinical outcomes of metastatic GC pts receiving first line CT according to histological classification (overall survival: OS and Progression Free Survival: PFS). Results: We analyzed 170 pts. Histological diagnosis was as follows: 24.1% (n=41) signet ring cell, 54.4% (n=92) diffuse type, 21.1%(n=37) intestinal type. Pts received a fluoropyrimidine-based doublet containing cisplatin, oxaliplatin or irinotecan; in three drugs regimen anthracycline was added. In diffuse type subgroup OS was: 11.3 months with oxaliplatin based CT, 7.3 months in cisplatin and 6.2 months in irinotecan (p=0.0054); PFS was 5.2, 3.5 and 4.4 months for oxaliplatin, cisplatin and irinotecan based CT respectively (p=0.0036). In signet ring cell carcinomas OS was 12.1 months with oxaliplatin 13.9 with irinotecan, and 5.6 months with cisplatin (p=0.04), and PFS was 6.5, 8.5 and 2.9 months in pts treated with oxaliplatin, cisplatin and irinotecan respectively (p=0.0008). Among pts with intestinal type we did not detect any significant difference in term of OS and PFS comparing first line schedules. Conclusions: Based on our results, histology may be used as a simple, costless and easy tool in advanced gastric cancer treatment management. Clinical use of biomarkers (with the exception for HER2) which are being evaluated as prognostic or predictive factors in GC, is still controversial. In this scenario, the prognostic / predictive value of histology could play a significant role in treatment decision making.
Validation of the postneoadjuvant therapy pathological stage of the American Joint Committee on Cancer (AJCC) 8th Edition for predicting outcomes of esophageal squamous cell carcinoma (ESCC) patients receiving neoadjuvant chemoradiotherapy (CRT) followed by esophagectomy.
Authors: Liu Tsung-hao , Kuo Hung-Yang , Guo Jhe-Cyuan , Lin Chia-Chi , Huang Ta-Chen , Hsieh Min-Shu , Lee Jang-Ming , Hsu Chih-Hung
Published: January 2019

138

Background: The AJCC 8th edition staging system introduces a new postneoadjuvant therapy staging category (ypTNM-8th) for ESCC patients receiving neoadjuvant treatment followed by esophagectomy. Whether this new staging category has better prognostic prediction than the pathological staging category of AJCC 7th edition (ypTNM-7th) needs validation. Methods: We enrolled ESCC patients receiving neoadjuvant paclitaxel/cisplatin-based CRT (RT = 40Gy) followed by esophagectomy from three phase II trials conducted in the National Taiwan University Hospital. The prognostic prediction abilities of the ypTNM-8th and the ypTNM-7th on patients’ survivals were compared using Cox regression, concordance index (C-index), R-square, and Akaike information criteria (AIC). Results: A total 135 patients (M:F = 127: 8, median age:53.0 years) were enrolled. With a median follow-up of 31.3 months, the median PFS and OS of all patients were 24.4 months (95% CI: 15.4-33.5) and 33.9 months (95% CI: 22.6-45.1), respectively. In univariate analysis, both ypTNM-8th and ypTNM-7th had statistically significant prognostic effects for PFS and OS. In multivariate analysis on OS, the ypTNM-8th demonstrated a statistically significant predicting effect (P = 0.015) while the ypTNM-7th did not (P = 0.051). Although there is no statistically different between ypTNM-8th and ypTNM-7th by R-square analysis, the ypTNM-8th had lower AIC and C-index for both PFS and OS, meaning an better efficiency of predicting survivals, than ypTNM-7th. Conclusions: The new ypTNM-8th may have better prognostic prediction for OS of locally advanced ESCC patients receiving neoadjuvant CRT than the ypTNM-7th. (Granted by 106-HCH029)
Gastric carcinoids: Does type of surgery or tumor affect survival?
Authors: Crown Angelena , Kanji Zaheer S. , Lopez-Aguiar Alexandra G , Dillhoff Mary , Poultsides George A. , Makris Eleftherios , Idrees Kamran , Marincola Smith Paula , Nathan Hari , Beems Megan , Weber Sharon M. , Fisher Alexander V , Fields Ryan , Davidson Jesse , Maithel Shishir , Rocha Flavio G.
Published: January 2019

139

Background: Gastric carcinoids are rare neuroendocrine tumors of the GI tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients. Methods: All patients who underwent resection of gastric carcinoids at 8 institutions from 2000-2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection LR or formal gastrectomy FG). Clinicopathological parameters, recurrence-free (RFS), and overall survival (OS) were compared between groups. Results: Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) had R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p < 0.04 and p < 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p < 0.017). This trend persisted when type II and type IV groups were excluded (p < 0.045). Conclusions: Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.
The clinical analysis of thromboembolism in esophagogastric cancer in Japan: A single institute experience.
Authors: Oguri Tomoyo , Takahari Daisuke , Ota Yumiko , Osumi Hiroki , Nakayama Izuma , Wakatsuki Takeru , Ogura Mariko , Ichimura Takashi , Suenaga Mitsukuni , Shinozaki Eiji , Chin Keisho , Yamaguchi Kensei
Published: January 2019

14

Background: Although patients with esophagogastric cancer have a higher risk of thromboembolism (TE), the clinical characteristics of esophagogastric cancer patients with TE remain unclear. Methods: We conducted a retrospective study of who were treated for TE in our institution from January 2014 to August 2017. Results: During this period, 1538 esophaogastic cancer patients received anti cancer therapy. Of these 62 (4.0%) patients diagnosed as having TE during their clinical course. Background of these patitents were median age :64.5 (28-87), gender male/ female: 36 /26, 47 had gastric cancer, 12 esophageal cancer, and 2 gastroesophageal cancer. Performance Status were 0/1/2/3 = 21/24/13/4. Clinical stage were Ⅳ 32 (metastatic sites; lymph nodes 7, peritoneal dissemination 6, ovary 4, liver 1), recurrence 18, and other 12 respectively. 26 patients did not have medical history, 15 had hypertension, 4 had diabetes mellitus, and 4 had hyperlipidemia. Pathologically, adenocarcinoma 50, squamous carcinoma 10, and other 2. Among patients with gastric cancer, 6 (12.8%) showed Her2 overexpression. The median D-dimer levels was 4.81(0.42-17.25) μg/ml. The onset of TE was before starting chemotherapy in 8(12.9%), during receiving chemotherapy in 48(77.4%), and during washout period in 6. On patients who developed TE during receiving chemotherapy, the regimens of chemotherapy were S-1 16, weekly paclitaxel 10 (plus ramucirumab 3), SOX 7, FP 4, Irinotecan 3, SP 3, FOLFOX 3, XP+Trastuzumab3, and others 9. The types of venous thrombosis were deep vein thrombosis 33, pulmonary embolism 23, central venous catheter 7, internal jugular vein 5, subclavian vein 4, and others 5. Four patients suffered cerebral infarction due to thrombosis of the arterial system thrombosis. Initial anticoagulation treatment for TE were heparin 33, warfarin 13, edoxaban 12 and other 4. 29 patients (46.8%) had no symptom related TE. Conclusions: In our analysis, 12.9% patients had TE before starting treatment, we should pay attention to TE immediately after diagnosis of esophagogastric cancer. As 46.8% patients have no symptom related TE, it is important to develop of biomarkers for screening TE, likely D-dimer.
Optimal surrogate endpoint of survival for gastric cancer patients undergoing neoadjuvant chemotherapy.
Authors: Hagi Takaomi , Kurokawa Yukinori , Miyazaki Yasuhiro , Takahashi Tsuyoshi , Tanaka Koji , Makino Tomoki , Yamasaki Makoto , Nakajima Kiyokazu , Mori Masaki , Doki Yuichiro
Published: January 2019

141

Background: Surrogate endpoint of survival for gastric cancer patients undergoing neoadjuvant chemotherapy (NAC) has not been established yet. To determine the most optimal surrogate endpoint, we compared the validity of outcomes according to the endoscopic or histological response criteria and other histological factors in gastric cancer patients who underwent NAC. Methods: The target population in this study was 77 gastric cancer patients who underwent NAC followed by curative gastrectomy between January 2010 and December 2016. In histological response criteria, if necrosis or disappearance of the tumor was present in more than 2/3 of the primary lesion, the case was diagnosed as a histological responder. Hazard ratio (HR) for RFS in responders according to each factor was estimated, and survival curves were compared between responders and non-responders using log-rank test. Results: The number of patients in each regimen was as follows: docetaxel/cisplatin/S-1, 40; docetaxel/oxaliplatin/S-1, 16; cisplatin/S-1, 15; S-1/oxaliplatin, 4; docetaxel/S-1, 2. The endoscopic and histological response rates were 73% (56/77) and 16% (12/77), respectively. The proportions of patients with ypT0-1 and ypN0 were 17% (13/77) and 23% (18/77), respectively. HRs were 0.761 (log-rank p = 0.43) in the endoscopic response criteria, 0.879 (log-rank p = 0.77) in the histological response criteria, 0.703 (log-rank p = 0.46) in ypT0-1, and 0.121 (log-rank p = 0.001) in ypN0, respectively. Three-year RFS rates in ypN status were ypN0/1/2/3 = 93%/48%/43%/14%. Conclusions: Pathological ypN status was the most optimal surrogate endpoint of RFS for gastric cancer patients undergoing NAC. Patients with ypN0 would be expected for long relapse-free survival.
Effects of apatinib dose interruptions on safety and efficacy in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of stomach or gastroesophageal junction in third- or later-line setting.
Authors: Wang Junsheng , Qin Shukui , Li Jin , Deng Wenying , Wen Lu , Zhang Guifang , Zhong Haijun , Jia Tongfu , Yang Jianwei , Bai Yuxian , Lin Xiaoyan , Wang Mei , Wang Lin , Liu Likun , He Yifu , Tao Min , Xie Congying , Ye Feng , Wu Xiang-yuan , Ba Yi
Published: January 2019

142

Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced gastric cancer in China. Due to toxicity, many pts underwent temporary interruptions during treatment. We analyzed the data from a phase IV clinical trial of Ahead-G201 to evaluate the relationship between dose interruption, drug safety and efficacy. Methods: At the cutoff date of Jul 10, 2017, Ahead-G201 study enrolled 1037 pts. The adverse events (AEs) and clinical efficacy were evaluated for pts with no, 1, 2 and ≥3 dose interruptions. Results: 336 of 1037 pts underwent dose interruptions during apatinib treatment: 1 interruption in 183 pts; 2 interruptions in 67 pts; and ≥3 interruptions in 86 pts. The toxicity and efficacy for them were listed in Table. For safety, pts with no interruption had the lowest incidence of all AEs (59.3%) and grade 3-4 AEs (30.0%). Pts with ≥3 interruptions had the highest objective response rate (ORR, 20.3%) and disease control rate (DCR, 82.6%). Moreover, these pts got median progression-free survival (mPFS) of 6.6 mos and median overall survival (mOS) of 9.4 mos, which were the longest among 4 groups. Furthermore, multivariate analysis revealed that ≥3 interruptions of apatinib bring much more efficacy benefit both in mPFS (6.6 vs 3.8 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.7) and mOS (9.4 vs 6.6 mos: hazard ratio, 0.5, 95%CI, 0.3 to 0.8) for pts, than those with no interruption. Conclusions: Current results indicated that dose interruptions are required to manage toxicity and it is necessary to explore an optimal dosing pattern of apatinib in advanced gastric cancer. Clinical trial information: NCT02426034. [Table: see text]
Association of radiomics and outcome in esophageal cancer following neoadjuvant chemo-radiation.
Authors: Eaford India , Rishi Anupam , Zhang Geoffrey , Viera Alexander , Latifi Kujtim , Frakes Jessica M. , Pimiento Jose Mario , Fontaine Jacques-Pierre , Hoffe Sarah E.
Published: January 2019

146

Background: Radiomic data extraction from medical images has the potential to differentiate tumor phenotypes. We investigated the potential of esophageal cancer radiomic features to differentiate clinical outcomes following neoadjuvant chemoradiation (NACRT). Methods: We retrospectively reviewed 68 biopsy-proven mid-distal esophageal/gastroesophageal junction (GEJ) cancer patients treated from 2007-2014 with NACRT followed by esophagectomy on an IRB approved study in which patients were eligible if imaging was performed at our institution. The primary tumor was segmented on baseline computed tomography (CT) and 18-Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) scans with contour review by two independent radiation oncologists. A total of 126 quantitative 3-D shape and intensity-based radiomics features were extracted using in-house data algorithm software. Locoregional control (LRC), metastasis free survival (DFS), metastasis free survival (MFS) and overall survival (OS) were estimated by Kaplan-Meier analysis and multivariate Cox proportion hazard. Results: Estimated actuarial 5-year RFS, LRC, MFS, OS was 56.6% (mean: 67.8 months, 95% CI 53.7-81.8 months), 83.1% (mean: 92.8 months, 95% CI 81.4-104.2 months), 64.9% (mean: 76.4 months, 95% CI 62.2-90.7 months), 39.5% (median survival 40 months, 95% CI 24.59-55.40), respectively. Pathological complete response (pCR) was achieved in 34 (50%) patients. Tumor Regression Grade (TRG) 0-1 indicative of complete response was associated with improved LRC [p = 0.04; Hazard Ratio (HR) 4.24 (1.01-19.01)]. On univariate analysis, 16 PET-based and 14 CT-based radiomics features were found to independently predict pCR. On multivariate analysis (MVA), three PET-CT based radiomic features [sphericity (p = 0.04), compactness (p = .05) and PET_TGV (p = 0.08)] were found to closely predict pCR. When grouped by median, PET sphericity independently predicted RFS [p = 0.014; Hazard Ratio (HR) 0.31 95% Confidence Interval (CI) 0.11-0.83]. Conclusions: This study suggests pre-treatment radiomic features in esophageal cancer may be prognostic for response assessment (pCR) and overall outcome following NACRT.
Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for nonresectable peritoneal carcinomatosis from gastric cancer.
Authors: Alyami Mohammad , Bonnot Pierre Emmanuel , Villeneuve Laurent , Bakrin Naoual , Glehen Olivier ,   BIG-RENAPE Working Group
Published: January 2019

149

Background: PIPAC is a recent approach for intraperitoneal chemotherapy with promising results for patients with peritoneal carcinomatosis (PC). We aimed to evaluate survival and postoperative outcome of PIPAC in patients with non-resectable PC from gastric cancer. Methods: This is a retrospective analysis. Sixty-nine PIPAC were applied in 22 consecutive patients pretreated non-resectable PC from gastric cancer. All patients had undergone previous lines of systemic chemotherapy (median, two lines). Cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were given for 30 min at 37 °C and 12 mmHg at 6-week intervals.The treatment schedule proposed alternating 2 systemic chemotherapy followed by 1 PIPAC cycles. Outcome criteria were survival, adverse events according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Results: At the time of the first PIPAC, the median PCI was 18 (1-35). Median consecutive PIPAC cycles were 4 (1-9). Survival time was 19.5 months. Major complications (CTCAE - III, IV) occurred for 6 PIPAC (8.7%) and 1 (4.5%) patients died within 30 days of the PIPAC procedure a cause related to aspiration pneumonia during the general anesthesia. Systemic chemotherapy was associated with PIPAC and could be administered after PIPAC with a median delay of 14 days (7-28). Conclusions: PIPAC with low-dose cisplatin and doxorubicin was safe and feasible in association with systemic chemotherapy. Survival data are encouraging and justify further clinical studies in this indication.
Next-generation sequencing to identify predictors of survival after trimodality therapy for esophageal cancer.
Authors: Oh Patrick , Zhang Minsi , Brady Paul , Sihag Smita , Molena Daniela , Ilson David H. , Janjigian Yelena Yuriy , Ku Geoffrey Yuyat , Wu Abraham Jing-Ching
Published: January 2019

153

Background: Tumor mutation profiling has changed the prognostication and treatment of a wide variety of malignances. However, little is known about whether mutation profiles affect outcome in localized esophageal cancer treated with multimodality therapy. SMAD4 is a gene involved in the regulation of the TGF-β signal transduction pathway by negatively controlling the growth of epithelial cells and has been implicated as a prognostic factor in pancreatic cancer. We undertook an exploratory analysis of tumor mutation profiles, including SMAD4 status, in localized esophageal cancer patients treated with trimodality therapy at our institution. Methods: We identified 66 Stage II-III esophageal cancer patients treated with chemoradiation followed by surgery who had some form of tumor mutation profiling available. Only patients with mutation profiling from pre-treatment biopsy or post-chemoradiation surgical specimen (i.e. not from a subsequent metastatic lesion) were included. Twenty-two patients underwent next-generation sequencing assessing 341 candidate genes via targeted sequencing. Log-rank test was used to assess correlation of mutations to overall survival, and to pathologic response. Results: The median follow-up was 17.1 months. SMAD4 loss was identified in 3 of 22 patients (13.6%) who underwent next-generation sequencing, and was significantly associated with inferior overall survival (p=0.023). No other candidate genes were significantly associated with survival, and no genes were significantly associated with pathologic response. Conclusions: To our knowledge, this is the first analysis of next-generation mutation profiling and outcome in non-metastatic esophageal cancer patients treated with trimodality therapy. Due to the limited numbers, this was an exploratory analysis only. We identified SMAD4 loss as a potential adverse prognostic factor for survival. More next-generation sequencing data from non-metastatic esophageal cancer patients treated with multimodality therapy is needed to further elucidate the potential relationship of SMAD4 loss or other mutations with outcome.
Phase Ib study of ramucirumab and irinotecan for metastatic gastric cancer previously treated with fluoropyrimidine with/without platina and taxane.
Authors: Sagawa Tamotsu , Satake Hironaga , Fujikawa Koshi , Hatachi Yukimasa , Yasui Hisateru , Kotaka Masahito , Kato Takeshi , Tsuji Akihito
Published: January 2019

155

Background: Optimal salvage line chemotherapy for previously heavily treated advanced/ metastatic gastric cancer (AGC) is unknown, but treated with irinotecan in Japan. Ramucirumab, a human IgG-1 monoclonal antibody that targets the extracellular domain of VEGF receptor 2, is the first molecularly targeted agent proven to be effective in second-line therapy for AGC in combination with chemotherapy. Furthermore, combination chemotherapy with ramucirumab and irinotecan based regimen (FOLFIRI) is recognized as one of the promising regimens for metastatic colorectal cancer. To date, however, use of the ramucirumab plus irinotean regimen for AGC patients has not been investigated, and recommended doses (RD) of ramucirumab plus irinotecan for patients with AGC therefore remain unknown. The aim of this study was to determine the maximum tolerated dose (MTD) and RD for systemic chemotherapy with rumucirumab plus irinotecan for AGC previously treated with fluoropyrimidine with/without platina and taxane. Methods: Patients received systemic chemotherapy with ramucirumab (8mg/kg) and irinotecan on day 1, repeated every 2 weeks. A decrease in irinotecan dose was planned from start level 1 (irinotecan 150mg/m2). This trial was registered with the University Hospital Medical Network (UMIN no. 000018606). Results: Six patients were enrolled from August 2015 to September 2017. MTD was not reached at level 1. Irinotecan 150 mg/m2 in combination with ramucirumab 8mg/kg could be administered with acceptable toxicity, and all patients were treated at these doses. No DLT was observed at Level 1. No treatment-related death was observed. Adverse events of grade 3/4 were neutropenia (17%), anemia (17%), hyponatremia (17%), hypertension (17%). Five of the six patients were evaluable for efficacy based on the RECIST criteria, and response rate and disease control rate were 20% and 100%, respectively. Conclusions: Salvage chemotherapy with a ramucirumab plus irinotecan regimen was well tolerable for patients with previously heavily treated AGC. RD was defined as ramucirumab 8 mg/kg in combination with irinotecan 150 mg/m2/day. Clinical trial information: 000018606.
Simulation study of volumetric modulated arc therapy for thoracic esophageal cancer using automated-radiotherapy planning software.
Authors: Murakami Yuji , Nagata Yasushi , Kimura Tomoki , Nishibuchi Ikuno , Nakashima Takeo
Published: January 2019

158

Background: To prevent cardiac toxicity after chemoradiotherapy for esophageal cancer (EC), decrease of high irradiation dose to the heart without expanding the volume of lung irradiated low dose is needed, but this is not easy under the conventional techniques. Purpose of this study is to investigate the utility of volumetric modulated arc therapy using automated-radiotherapy planning software (auto-VMAT) to solve this issue. Methods: In this simulation study, data of 12 patients with stage I-III ECs previously treated by 3D-conformal radiotherapy (3DCRT) was used. We performed auto-VMAT planning using commercially available ‘Pinnacle3 Auto-Planning’ software. Targets for gross tumor (PTV1) and elective nodal region (PTV2), and organs at risk (OARs: lung, heart, left ventricle, epicardium, left pleura, liver and spinal cord) were delineated. Multi-portal beams were used for 3DCRT and dose description was 40 Gy in 20 fractions for PTV1+2 and 20 Gy in 10 fractions-boost for PTV1. We used the simultaneous integrated boost method for auto-VMAT with a dose description of 60 Gy for PTV1 and 48 Gy for PTV2 in 30 fractions. We performed planning in consideration with decrease of volumes irradiated middle to high dose in left ventricle and achievement of volume irradiated 5 Gy (V5) in lung < 50% as high-priority dose constraints. Results: Prescribed dose coverage of PTVs was equivalent between 3DCRT and auto-VMAT, while auto-VMAT showed better dose-conformity. Auto-VMAT showed a significant decrease of mean dose and V20-V60 in heart, left ventricle and epicardium and significant decrease of V50-V60 in lung and left pleura. V5 in lung was equivalent between 3DCRT and auto-VMAT (46.6±9.6% vs 45.6±4.7%; p = 0.72). Auto-VMAT achieved the V5 in lung < 50% in 10 among 12 patients and the max V5 in lung was 52.5%. Conclusions: Auto-VMAT for ECs achieved better dose conformity of targets, decrease of middle-high dose in heart, left ventricle and epicardium, and equivalent low dose volumes in lung. Auto-VMAT planning brings high quality dose distribution, uniformity of quality of planning, laborsaving and timesaving in treatment planning.
Body mass index and mortality in patients with gastric cancer: A large cohort study.
Authors: Lee Jung Hwan , Park Boram , Joo Jungnam , Kim Young-Il , Kim Chan Gyoo , Lee Jong Yeul , Choi Il Ju , Yoon Hong Man , Eom Bang Wool , Ryu Keun Won , Kim Young Woo , Cho Soo-Jeong
Published: January 2019

16

Background: Although excess body weight has been known to be an important risk factor for mortality from many cancers including colorectal, endometrial and breast cancers, the prognosis of gastric cancer (GC) in obese patients seems controversial. Methods: We aimed to evaluate the association between body mass index (BMI) and mortality in GC in a large cohort. A single institute cohort of 7,765 GC patients undergoing curative gastrectomy between October 2000 and June 2016 were categorized into 6 groups; underweight (< 18.5 kg/m2), normal (18.5 to < 23 kg/m2), overweight (23 to < 25 kg/m2), obese I (25 to < 28 kg/m2), obese II (28 to < 30 kg/m2), and severely obese (≥30 kg/m2). The hazard ratios (HRs) for overall survival and disease-specific survival were calculated using Cox proportional hazard model. Results: We identified 1,279 all-cause and 763 disease-specific deaths among 7,765 patients, and the median follow-up period was 83.05 months (range, 1.02-186.97 months). In multivariable analyses adjusted by age, sex, tumor stage, comorbidity and operation methods, preoperative BMI was associated with all-cause mortality in a nonlinear pattern. As compared with patients who were normal weight, underweight BMI showed increasing mortality risk (hazard ratio (HR), 1.42, 95% confidence interval (CI), 1.15-1.77). In contrast, patients who were overweight (HR, 0.84; 95% CI, 0.73-0.97), obese I (HR, 0.77; 95% CI, 0.66-0.90) and obese II (HR, 0.77; 95% CI, 0.59-1.01) had lower risk of mortality. disease-specific mortality also had a similar pattern to overall survival showing the lowest mortality in obese II group (HR, 0.59; 95% CI, 0.40-0.88). There was no significant difference in severely obese patients in both all-cause and disease-specific mortalities. In spline analyses illustrated by a bell-shaped curve, risk for all-cause mortality was the lowest in patients with 26.67 kg/m2. Conclusions: Preoperative overweight and obese patients (23 to < 30 kg/m2) had lower all-cause and disease-specific mortalities compared to those with normal weight in GC patients who underwent curative surgical resection.
Surgical outcomes and learning curve analysis of robotic gastrectomy for gastric cancer: multidimensional analysis in a comparison with 3D laparoscopic gastrectomy.
Authors: Chen Lin , Li Jiyang , Guo Xin , Xi Hongqing , Gao Yunhe , Cui Jianxin , Qiao Zhi , Zhang Kecheng , Liang Wenquan , Wei Bo , Xie Tianyu
Published: January 2019

162

Background: There is a lack of supporting evidence regarding the safety, efficacy and surgeon acceptance of robotic versus three-dimensional (3D) laparoscopic surgery for patients with gastric cancer (GC). Methods: An ambispective cohort study was conducted. We compared short-term surgical outcomes including financial cost between robotic and 3D laparoscopic gastrectomy for all GC patients and the GC patients treated by Prof. Chen’s team. The Cumulative Sum (CUSUM) method was developed and used to analyze the learning curves of robotic and 3D laparoscopic gastrectomy performed by Prof. Chen. Results: From August 2011 to June 2017, a total of 517 patients were enrolled for treatment with either robotic (n=408 including n=73 performed by Prof. Chen) or 3D laparoscopic (n=109 including n=71 performed by Prof. Chen) gastrectomy. There were no significant differences between the two operation methods regarding the clinical pathological characteristics, except for smoking habit (p < 0.001). In analysis of all the 517 patients, robotic group had shorter operative time (208 min vs 228 min, p=0.004), less time to first flatus (3 days vs 4 days, p=0.025), longer time to remove drainage and nasogastric tube (12 days vs 9 days, p=0.001, 6 days vs. 4 days, p=0.001, respectively), and more postoperative complications (21.3% vs. 9.2%, p=0.003). While we compared these short-term outcomes of robotic and 3D laparoscopic gastrectomy performed by Prof. Chen, only number of lymph node dissections (robotic 27 vs. 3D 33, p=0.038) and time to remove nasogastric tube (robotic 5 days vs. 3D 3 days, p < 0.001) were significantly different. CUSUM analysis showed that operative time reached a stable state after around 21 cases in robotic gastrectomy and 19 cases in 3D laparoscopic gastrectomy. The cost-effectiveness analysis showed that robotic gastrectomy had significantly higher total cost than 3D laparoscopic gastrectomy (robotic = RMB 124907 vs. 3D-laparoscopic = RMB 94395; p < 0.001). Conclusions: With comparable surgical outcomes, higher surgeon acceptance and less financial cost, 3D laparoscope is a highly recommended minimal invasive surgical method for GC patients.
Management of metastatic gastric and esophageal cancer in older adults.
Authors: Yokom Daniel , Natori Akina , Sim Hao-Wen , Chan Bryan Anthony , Moignard Stephanie , Sun Peiran , Lim Charles Henry , Jiang Di Maria , Ma Lucy Xiaolu , Darling Gail Elizabeth , Swallow Carol Jane , Brierley James D. , Wong Rebecca , Liu Geoffrey , Chen Eric Xueyu , Knox Jennifer J. , Alibhai Shabbir M.H. , Jang Raymond Woo-Jun , Elimova Elena
Published: January 2019

163

Background: Older adults are under-represented or excluded from pivotal trials of palliative chemotherapy for metastatic gastric and esophageal (GE) cancers. Little is known about how older patients are treated in the real world. The objective of this study was to examine the impact of age on treatment and survival. Methods: Patients aged ≥65 years were identified from a retrospective database of patients with metastatic GE cancer (Princess Margaret Cancer Centre; 2011-2016). The impact of age ≥75 years (old-old) versus (vs.) 65-74 years (young-old) on treatment and survival was assessed using multivariable logistic and Cox proportional hazard regression models, respectively, adjusted for known prognostic factors including sex, comorbidity, primary site, histology, grade, stage at initial diagnosis, metastatic sites, and chemotherapy use. Results: Of 183 patients, median age was 72 (range 65-92) years; 31% were old-old. Old-old patients were less likely to be treated with any chemotherapy (12.3% vs. 45.2% young-old; adjusted odds ratio = 0.12 (95% confidence interval (CI) 0.05-0.31)). With a median follow-up of 5.7 months, 135 (74%) had died during follow-up; median overall survival (OS) was 5.2 months (mo) for the old-old vs. 8.4 mo (young-old). There was no significant difference in survival between the two groups after adjustment for known prognostic factors (old-old vs. young-old: univariable hazard ratio (HR) 1.75 (95% CI 1.2-2.5); adjusted HR 1.1 (95% CI 0.7-1.7). Treatment with any chemotherapy was associated with an improvement in survival: adjusted HR 0.34 (95%CI 0.22-0.52). Conclusions: In this single-centre study of older adults with metastatic GE cancer, there was an overall low rate of treatment with chemotherapy; those ≥75 were rarely treated. After accounting for known prognostic factors, there was no observed difference in survival between patients ≥75 and those 65 to 74. Comprehensive geriatric assessment may improve treatment selection in the older population. [Table: see text]
Screening for cancer-associated dysphagia: The development of two rapid tools for use in observational studies and routine care.
Authors: Borean Michael , Shani Kishan , Brown M. Catherine , Chen Judy , Liang Mindy , Karkada Joel , Kooner Simranjit , Doherty Mark K. , O'Kane Grainne M. , Jang Raymond Woo-Jun , Elimova Elena , Wong Rebecca , Darling Gail Elizabeth , Xu Wei , Howell Doris , Liu Geoffrey
Published: January 2019

164

Background: Dysphagia as a cancer symptom can be associated with significant morbidity. We developed dysphagia screener tools for use in observational studies (Phase 1) and routine symptom monitoring in clinical care (Phase 2). Methods: Various dysphagia or odynophagia screening questions, selected after an expert panel reviewed content, criterion, and construct validity, were compared to either FACT-E Swallowing Index Cut-Off Values (SICV) or to questions adapted from the Patient Reported Outcomes for Common Terminology Criteria for Adverse Events (PRO-CTCAE). Sensitivity, specificity and patient acceptability were assessed. Results: In developing a tool for observational studies (Phase 1; n = 178 esophageal cancer patients), the screening question, “How are you currently eating?” had the highest sensitivities and specificities against various SICV cut-offs, with the best optimal cut-off associated with the clinical outcome of weight loss (80% sensitivity, 75% specificity). When developing a rapid screening tool for routine symptom monitoring (Phase 2; 255 head and neck, gastro-esophageal, and patients undergoing thoracic radiation), a single question screener (“Do you experience any difficulty or pain upon swallowing?”) versus a PRO-CTCAE-like gold standard generated sensitivities between 86-94% and specificities between 93-100%. The screening question (+/- follow-up questions where indicated) had a median completion time of under 2 minutes, and > 90% of patients were happy to complete the survey on an electronic tablet, did not feel that survey completion made their clinic visit more difficult, and did not find the questions upsetting or distressful. Conclusions: Two screener tools (for prospective observational studies “How are you currently eating?”, and for routine clinical monitoring “Do you experience any difficulty or pain upon swallowing?”) can effectively screen dysphagia symptoms without increasing cancer outpatient clinic burden.
Morbidity and mortality outcomes after esophagectomy following chemoradiation using a standardized operative technique.
Authors: Ha Jinny Suk , Fraser Charles , Zhou Xun , Hansaraj Natasha , Burrows Whitney , Broderick Stephen , Battafarano Richard James
Published: January 2019

166

Background: Esophagogastrectomy following neoadjuvant chemo-radiation therapy for the treatment of locally advanced esophageal cancer is associated with significant morbidity and mortality. We hypothesized that the avoidance of neck anastomoses unless absolutely necessary to achieve negative margins and standardization of the anastomotic technique among surgeons would significantly decrease perioperative morbidity and potential mortality and improve oncologic outcomes for these patients. Methods: A HIPAA-compliant, prospectively maintained data base was retrospectively analyzed on 115 patients who underwent esophagogastrectomy following chemo-RT from 2007-2017 performed via a laparotomy and right thoracotomy using a standardized anastomotic technique. These procedures were performed by 5 different attending surgeons at 2 different academic medical centers. Peri-operative morbidity was assessed by standard measures and post-operative survival was assessed using Kaplan-Meyer survival. Results: There was 1 anastomotic leak and 1 mortality at 30 and 90 days. The overall 5-year survival was 40%. Major morbidity, defined as re-operation for bleeding, anastomotic leak, pneumonia, reintubation, chyle leak, and initial mechanical ventilation > 48 hours was 26% (30/113). Conclusions: Low anastomotic complication rates are associated with decreased perioperative morbidity and prolonged oncologic survival when compared to historical controls.