bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival prediction in patients treated by FOLFIRI and bevacizumab for metastatic colorectal cancer (PRODIGE 9) using contrast-enhanced CT texture analysis (SPECTRA).
Authors: Dohan Anthony , Gallix Benoit , Guiu Boris , Le Malicot Karine , Reinhold Caroline , Soyer Philippe , Bennouna Jaafar , Ghiringhelli Francois , Boige Valerie , Taieb Julien , Bouche Olivier , Francois Eric , Phelip Jean Marc , Borel Christian , Faroux Roger , Seitz Jean-François , Jacquot Stephane , Lepage Come , Aparicio Thomas , Hoeffel Christine 
Published: September 2018

3601 Background: Quantitative assessment of tumor architecture changes may help to early identify non-responder patients and propose a tailored treatment strategy. Our objective was to build and validate a radiomics signature able to predict early the lack of response to chemotherapy including FOLFIFRI and bevacizumab using baseline and first evaluation CT and to compare it to the RECIST and morphological criteria. Methods: For 230 patients of PRODIGE 9 study and treated by FOLFIRI and bevacizumab, a computed analysis (CA) was performed on the dominant liver lesion (DLL) at baseline and 2 months post-chemotherapy. RECIST evaluation was performed at 2 and 6 months. The sum of the target liver lesions (STL), the density of the DLL, CA parameters and their changes rates were correlated with the 2-year survival status. A radiomics signature combining 3 parameters was built in one arm and validated in the second arm. Survival was estimated with the Kaplan-Meier method and compared with log-rank test. Results: The strongest predictive factors for 2-year survival status were decrease in STL(AUC = .69±.05[95%CI:.60-.77]), change rate in kurtosis(ssf = 0) (AUC = .66±.05[95%CI:.57-.74]), and the baseline density of the DLL (AUC = .68±.05[95%CI:.59-.77]). Using multivariate analysis, predictive factors of 2-year survival status were the decrease in STL > 15%(HR = 1.92, P= .002), the increase in kurtosis value(ssf = 0) > 93% (HR = 2.16, P= .001), and baseline DLL > 64.3UH (HR = 1.70, P= .02). Then, the SPECTRA-score was built by according 1 point for each of the 3 criteria. Patients with a SPECTRA-score > 1 had a lower overall survival in the training ( P= .001) and in the validation cohort ( P= .002). Non-response according to RECIST at 6 months had the same prognostic value as SPECTRA-score>1 at 2 months. Conclusions: A radiomics signature combining STL, density and CA on baseline and first evaluation CT is be able to predict which patient will have a poor outcome with same performances than standard evaluation with RECIST1.1 at 6 months in mCRC patients. Clinical trial information: NCT00952029.
Prognostic impact of tumor budding in stage II colon cancer: A prospective study (SACURA trial).
Authors: Ueno Hideki , Ishiguro Megumi , Nakatani Eiji , Ishikawa Toshiaki , Uetake Hiroyuki , Murotani Kenta , Matsui Shigeyuki , Tomita Naohiro , Shimada Yasuhiro , Takahashi Keiichi , Kotake Kenjiro , Watanabe Masahiko , Mochizuki Hidetaka , Teramukai Satoshi , Sugihara Kenichi ,   SACURA Study Group
Published: September 2018

3609 Background: Growing number of studies indicate tumor budding is a significant prognostic factor in colorectal cancer (van Wyk, et al. Cancer Treat Rev 2015), but this has been shown only in retrospective studies. We prospectively evaluated prognostic factors in stage II colon cancer to determine their prognostic value in a multi-institutional phase III study (SACURA trial, ASCO2016 abst#3617). Methods: A total of 991 patients with curatively resected stage II colon cancer (2006–2010; 136 institutions) were included in the study. Tumor budding was defined as an isolated cancer cell or a cluster composed of fewer than five cells in the invasive frontal region, and was graded based on its number within a microscopic field of a 20x objective lens (0.785 mm2) in the hotspot. Tumors with < 5, 5–9, and ≥10 budding foci were classified as grades G1, G2, and G3, respectively. All clinical and pathological data including the grade of budding were prospectively recorded and prognostic analyses were performed at 5 years after the completion of registration. Results: According to budding grading, 376, 331 and 284 tumors were classified as G1, G2, and G3, and 5-year relapse-free survival (RFS) rate was 90.9%, 85.1%, and 74.4%, respectively ( P < 0.0001). Budding grade was significantly associated with the incidence of recurrence in the liver, lung, lymph node, and peritoneum ( P < 0.0001–0.01). Among conventional factors, T stage and the serum CEA levels were associated with RFS, however, tumor grade, lymphatic and venous invasions, and the number of lymph node examined were not significant factors. Multivariate analysis for RFS showed budding, along with T stage, exerted an independent influence on prognostic outcome. Budding grade surpassed T stage and tumor grade in the ability to stratify patients by RFS (Harrell’s c-index, 0.63, 0.59, and 0.54, respectively). Conclusions: Our prospective study indicates that the grade of tumor budding is more informative for prognostic prediction than conventional prognostic factors in stage II colon cancer. The role of this prognostic factor should be highlighted in the adjuvant treatment setting, and conversely, some of prognostic factors adopted in clinical guidelines may need to be reconsidered. Clinical trial information: NCT00392899.
Recurrence risk factors and outcome stratification in stage II colon cancer patients: A subanalysis of the SACURA trial.
Authors: Ishiguro Megumi , Nakatani Eiji , Ueno Hideki , Ishikawa Toshiaki , Uetake Hiroyuki , Shimada Yasuhiro , Takahashi Keiichi , Kotake Kenjiro , Watanabe Masahiko , Tomita Naohiro , Mochizuki Hidetaka , Teramukai Satoshi , Sugihara Kenichi 
Published: September 2018

3611 Background: Efficacy of adjuvant chemotherapy for stage II colon cancer is still controversial. We conducted the SACURA trial, a phase III study which evaluated the superiority of 1-year adjuvant treatment with oral tegafur-uracil (UFT) to surgery alone in stage II colon cancer. However, survival benefit of 1-year UFT to surgery alone was not demonstrated (ASCO2016 abst#3617). We herein aimed to identify risk factors for recurrence in the stage II patients “without adjuvant chemotherapy”, and to stratify the prognosis by using these factors. Methods: Among a total of 982 patients without adjuvant chemotherapy enrolled to the SACURA trial, we extracted the factors correlated to recurrence using a univariate and multivariate Cox proportional hazard model. 943 and 935 patients in the surgery alone group and UFT group were divided to subgroups according to the number of risk factors, and the recurrence rate in each subgroup was evaluated. Results: Among the conventional clinicopathological characteristics, the multivariate analysis identified pT4, elevated CEA, and examined lymph nodes less than 12 as significant risk factors for recurrence. The rate of patients with 0, 1, 2, and 3 risk factors were 45.0%, 42.4%, 11.5%, and 1.1%, respectively. The recurrence rate for each subgroup was shown in the table: the recurrence rate increased with number of risk factors, while 10.2% of patients without any risk factors developed recurrence. Difference in the recurrence rate between the treatment groups was significant in patients without risk factor, marginal in patients with 1 risk factor, and none in patients with >1 factors. Conclusions: pT4, elevated CEA, and examined lymph nodes less than 12 were identified as risk factors for recurrence in stage II colon cancer patients. The recurrence rate was divided by the number of these risk factors, but we could not extract the very-low risk group in whom adjuvant therapy is unnecessary. Induction of novel risk factors other than conventional clinicopathological characteristics is recommended. Clinical trial information: NCT00392899. [Table: see text]
Clonal evolution in locally advanced rectal cancers in response to neoadjuvant chemoradiotherapy.
Authors: Toomey Sinead , Carr Aoife , Gunther Jillian Rebecca , Fay Joanna , O'Grady Anthony , Weksberg David , Piraino Scott W , Kay Elaine , O'Neill Brian , Krishnan Sunil , Furney Simon J , Hennessy Bryan 
Published: September 2018

3616 Background: Locally advanced rectal cancer, LARC (T3/4 and/or N+) is currently treated with neoadjuvant chemoradiotherapy (NACRT), however clinicopathological response is variable. Monitoring clonal evolution in response to NACRT may identify mutations driving therapeutic resistance or tumor growth after treatment. Methods: Fresh-frozen pre- and post-NACRT tumor and matched normal tissue from LARC patients were stratified into good (RCPath A), intermediate (RCPath B) and poor (RCPath C) responders. Following histological review, targeted exome capture was performed using an Agilent SureSelect Human all Exome V3 kit. Samples were sequenced to a minimum of 100X coverage on an Illumina HiSeq2000, and clonal evolution was assessed in matched pre- and post-NACRT tumor samples. Results: The median somatic mutation burden in pre-treatment samples was 114 (IQR 19-207). Two tumors were microsatellite (MSI) unstable and had elevated mutational burdens. The least evolution occurred in the poor responders, where there was little change in clonal composition after treatment, and driver mutations in genes including TP53 and APC were retained. On average 79% of pre-treatment mutations were retained post-treatment in poor responders and 33% of mutations were retained in intermediate responders. Many of the intermediate responders had loss of driver mutations including TP53 from the pre-treatment sample, but also shared a number of mutations in genes including PIK3CA and BRAF between pre- and post-treatment samples. There was also increased frequency in the post-treatment samples of clones that were not present in the pre-treatment samples. In one intermediate responder, all 47 mutations that were present in the pre-treatment sample including the driver mutations TP53 and APC were absent in the post-treatment sample, while 10 completely new mutations were identified. Conclusions: Dynamic mutational processes occur in LARC following selective pressures of exposure to NACRT, including changes in somatic mutation presence or frequency after treatment, owing to persistence or loss of sub-clones. As NACRT can profoundly affect the LARC genome, monitoring molecular changes during treatment may be clinically useful.
Phase III multi-centre open-label randomized controlled trial of selective internal radiation therapy (SIRT) versus sorafenib in locally advanced hepatocellular carcinoma: The SIRveNIB study.
Authors: Chow Pierce H. W. , Gandhi Mihir ,   Asia-Paciifc Hepatocellular Carcinoma Trials Group
Published: September 2018

4002 Background: The optimal therapeutic regime for locally advanced hepatocellular carcinoma (HCC) with and without vascular invasion remains unclear. This study evaluates the efficacy of Selective Internal Radiation Therapy using SIR-Spheres yttrium-90 microspheres (Y90) versus sorafenib in Asian Barcelona Clinic Liver Cancer (BCLC) stage B and C patients without extra-hepatic metastasis. Methods: This investigator-initiated multi-center trial randomized eligible patients with locally advanced inoperable HCC to single injection of Y90 or sorafenib (oral 400mg BD) till progressive disease or unacceptable toxicity. The sample size, assuming type I error (two-sided) of 0.05 and power of 90% was 360 patients. Final analysis was planned at 266 reported deaths. Results: 360 patients (182 Y90, 178 sorafenib) were enrolled from 27 centers in 11 Asian countries. BCLC C patients without extra-hepatic metastasis comprised 41.4% of patients, 30.6% had portal vein thrombosis (PVT), 88.6% were Child-Pugh A, 57.2% were hepatitis B and 15.0% were hepatitis C. Altogether 28.6% and 9.0% of patients in the Y90 and sorafenib arms respectively failed to receive planned therapy. Intention-to-treat analysis was carried out with the overall survival (OS) in the Y90 and sorafenib arms being 8.54 and 10.58 months respectively (Hazard ratio (HR) 1.17, p =0.203). Tumour response rate (TRR) was 16.5% and 1.7% (p < 0.001) respectively. Time-to-tumor -progression (TTP) was 5.88 vs 5.36 (overall) (HR 0.93) and 6.08 vs 5.39 (liver-specific) (HR 0.91) months for Y90 and sorafenib respectively. Progression-free-survival (PFS) was 5.29 vs 5.06 (overall) (HR 0.94) and 5.85 vs 5.06 (liver-specific) (HR 0.92) months respectively. At least one severe adverse event was found in 27.7% and 50.6% of patients in the Y90 and sorafenib arms respectively. Conclusions: Asian patients with locally advanced HCC without extra-hepatic metastasis treated with Y90 have statistically significant better TRR, and fewer SAEs when compared with those treated with sorafenib. There were no statistically significant differences in OS between Y90 and sorafenib. Clinical trial information: NCT01135056.
Intergroup phase III trial of neo-adjuvant chemotherapy, followed by chemoradiation and surgery with and without cetuximab in locally advanced esophageal carcinoma: First results from the SAKK 75/08 trial.
Authors: Ruhstaller Thomas , Thuss-Patience Peter C. , Hayoz Stefanie , Schacher-Kaufmann Sabina , Riera-Knorrenschild Jorge , Schnider Annelies , Plasswilm Ludwig , Budach Wilfried , Eisterer Wolfgang , Hawle Hanne , Mariette Christophe , Hess Viviane , Mingrone Walter B. , Wagner Anna Dorothea , Girschikofsky Michael , Schmidt Sven-Christian , Bitzer Michael , Bedenne Laurent , Brauchli Peter , Stahl Michael ,   Swiss Group for Clinical Cancer Research (SAKK), German Esophageal Cancer Study Group, Austrian "Arbeitsgemeinschaft Medikamentose Tumortherapie" (AGMT), Federation Francophone de Cancerologie Digestive (FFCD)/Federation de Recherche en Chirurgie (FRENCH)
Published: September 2018

4019 Background: We compared chemoradiotherapy followed by surgery with the addition of neoadjuvant and adjuvant cetuximab (cetux) in patients with esophageal carcinoma. Methods: Pts with resectable esophageal cancer (T2N1-3;T3-4aNx) received two cycles of induction chemotherapy (docetaxel 75mg/m2, cisplatin 75mg/m2) followed by chemoradiation (45 Gy, docetaxel 20mg/m2 and cisplatin 25mg/m2 weekly) and surgery or the same treatment with addition of neoadjuvant cetux 250mg/m2 weekly and adjuvant cetux 500mg/m2 bi-weekly for three months. Primary endpoint was progression-free survival (PFS). After a median follow-up of 4y 166 of the planned 180 events occurred (plateau reached). Results: 300 pts were treated between 2010-13: 88% male, median age 61y, 63% adenocarcinoma, 85% cT3/4a, 90% cN+. 84% completed neoadjuvant therapy, 87% were operated (cetux: 89%, control: 86%), 67% started and 50% completed adjuvant cetux-therapy. The R0 resection rate was 95% in the cetux-arm and 97% in the control-arm, there were 10 and 14 treatment-related deaths and 9 and 4 postoperative in-hospital deaths, respectively. Major differences in adverse events (grade >2) with addition of cetux were higher rate of allergic reactions and hypomagnesemia, but lower rate of dysphagia (-15%) and esophagitis (-4%) during chemoradiation. Conclusions: The addition of cetuximab to a multimodal therapy showed a statistically significant reduction of loco-regional recurrences which led to a statistically non-significant, but clinically relevant improvement of PFS and OS. Clinical trial information: NCT01107639. [Table: see text]
Short-term outcomes from a multi-institutional, phase III study of laparoscopic versus open distal gastrectomy with D2 lymph node dissection for locally advanced gastric cancer (JLSSG0901).
Authors: Lee Sang-Woong , Etoh Tsuyoshi , Ohyama Tetsuji , Inaki Noriyuki , Sakuramoto Shinichi , Yoshida Kazuhiro , Koeda Keisuke , Hosoda Kei , Kunisaki Chikara , Kojima Kazuyuki , Yasuda Takashi , Takagane Akinori , Misawa Kazunari , Kinoshita Takahiro , Yajima Kazuhito , Takiguchi Shuji , Hiki Naoki , Shiraishi Norio , Kitano Seigo ,   The Japanese Laparoscopic Surgery Study Group
Published: September 2018

4029 Background: The safety of laparoscopic gastrectomy for advanced gastric cancer is controversial. We conducted a multi-institutional, randomized controlled trial to compare short- and long-term outcomes of laparoscopic distal gastrectomy (LAP) with D2 lymph node dissection for advanced gastric cancer in comparison to open distal gastrectomy (OP) in Japan (UMIN000003420). We herein demonstrate short-term outcomes of this trial. Methods: Patients with potentially curable gastric cancer (T2-T4, N0-2 and M0) by distal gastrectomy were eligible for inclusion. Between November 2009 and July 2016, 507 patients were randomly assigned to either the LAP group (n = 252) or the OP group (n = 255). Only credentialed surgeons in both the procedures from 37 Japanese institutions participated in the study. The primary endpoint was 5-year relapse free survival. Secondary endpoints were 5-year overall survival, adverse events and short-term clinical outcomes. Results: According to study protocol, 47 patients among the total eligible patients were excluded because of distant metastasis or tumor extension intraoperatively. The remaining 460 patients underwent distal gastrectomy with D2 lymph node dissection and were analyzed as per protocol. Estimated blood loss was lower in LAP than in OP (30 vs. 150 ml, P < 0.001) and operative time was longer in LAP than in OP (291 vs. 205 min, P < 0.001). Post-operative analgesics use was less in LAP than in OP (38.3 vs. 53.6 %, P = 0.001), and first day of flatus was shorter in LAP than in OP (2 vs. 3 days, P < 0.001). There were no significant differences in all grade intra-operative complications (LAP 0.9% vs. OP 2.6%, P = 0.285). In addition, there were no significant differences in grade 3 and higher post-operative complications between the two groups (LAP 3.1% vs. OP 4.7%, P = 0.473). Hospital mortality was 0.4 % in each group. Conclusions: Credentialed surgeons could safely perform laparoscopic distal gastrectomy with D2 lymph node dissection for locally advanced gastric cancer. The laparoscopic approach could be accepted without increasing major surgical complications in this setting. Clinical trial information: 000003420.
Phase II study of intraperitoneal docetaxel plus capecitabine/cisplatin for gastric cancer with peritoneal metastasis: XP+IP DOC trial.
Authors: Fukushima Ryoji , Ishigami Hironori , Miwa Hiroto , Imano Motohiro , Kobayashi Daisuke , Tsuji Yasushi , Hidemura Akio , Kusumoto Tetsuya , Omori Takeshi , Yabusaki Hiroshi , Ohashi Norifumi , Ota Mitsuhiko , Yamaguchi Hironori , Kitayama Joji ,   Japan Intraperitoneal Chemotherapy Study Group (JIPG)
Published: September 2018

4039 Background: Intraperitoneal (IP) chemotherapy with taxanes provides sustained high local concentrations, and the efficacy of IP paclitaxel (PTX) has been shown in ovarian cancer. We previously reported the safety and efficacy of IP PTX plus systemic chemotherapy in clinical trials. Capecitabine/cisplatin (XP) is one of the standard regimens for the first-line treatment of advanced gastric cancer worldwide. We designed a new regimen combining IP docetaxel (DOC) with XP, and the recommended dose of IP DOC was determined to be 10 mg/m2 in a phase I study. A phase II study of XP plus IP DOC was performed in gastric cancer patients with peritoneal metastasis. Methods: Gastric cancer patients with peritoneal metastasis confirmed by diagnostic imaging, laparoscopy or laparotomy were enrolled. DOC was administered intraperitoneally at 10 mg/m2 on days 1 and 8. Cisplatin was administered intravenously at 80 mg/m2 on day 1, and capecitabine was administered at 1000 mg/m2 bid for 14 consecutive days, repeated every 21 days. The primary endpoint was the 1-year overall survival (OS) rate. Secondary endpoints were response rate, negative conversion rate on peritoneal cytology and safety. Results: Out of 50 patients enrolled, 48 patients received protocol treatment, and were evaluated for OS and toxicity. The median number of courses was 6 (range 1-15). The 1-year OS rate was 75% (95% confidence interval, 60-85%). The best overall response was stable disease in all the three patients with target lesions. Cancer cells ceased to be detected by peritoneal cytology in 28 (76%) of 37 patients. Nineteen patients underwent gastrectomy after response to chemotherapy. The incidences of grade 3/4 hematological and non-hematological toxicities were 42% and 48%, respectively. The frequent grade 3/4 toxicities included neutropenia (21%), leukopenia (8%), anemia (29%), anorexia (25%) and nausea (17%). Infection of the intraperitoneal port was observed in one patient. There were no treatment-related deaths. Conclusions: Combination chemotherapy of XP plus IP DOC regimen is well tolerated and active in gastric cancer patients with peritoneal metastasis. Clinical trial information: UMIN000016469.
Prognostic and predictive factors for overall survival (OS) in metastatic esophagogastric cancer (EGC): A meta-analysis.
Authors: ter Veer Emil , van Kleef Jessy Joy , Schokker Sandor , Van Der Woude Stephanie , Laarman Marety , Haj Mohammad Nadia , van Oijen Martijn G.H. , Van Laarhoven Hanneke W.M. 
Published: September 2018

4048 Background: Prognostic and predictive factors for metastatic EGC are important to estimate prognosis, inform clinical decision-making and design future trials. We performed a systematic review with meta-analysis to identify these factors. Methods: We searched Medline, EMBASE and CENTRAL for phase 2/3 randomized controlled trials (RCTs) until January 2016 on palliative chemotherapy and targeted therapy for metastatic EGC. Prognostic and predictive factors were identified from respectively multivariate cox regressions and stratified treatment comparisons. Hazard Ratio’s (HR) for OS were extracted and pooled with meta-analysis if possible. Prognostic factors were considered independent if the multivariate HR was significant (P≤0.05). Predictive factors were clinically relevant if P for subgroup interaction was ≤0.20 and the HR in one of the subgroups was significant (P≤0.05). Results: We identified 47 RCTs (14,853 patients), wherein 54 potential prognostic and 40 predictive factors were reported. Eight independent prognostic factors for poor OS reported in ≥2 RCTs based on ≥300 patients were: performance status of ≥1 vs 0 (pooled HR, 95% confidence interval: 1.47, 1.25-1.73) or 2 vs 0-1 (1.52, 1.32-1.76); metastatic vs locally advanced disease (1.55, 1.39-1.72); diffuse vs intestinal/other histology (1.38, 1.12-1.71); ≥3 vs < 2 metastatic sites (1.35, 1.07-1.70); presence of metastases in peritoneum (1.24, 1.01-1.51) or liver (1.45 (1.28-1.64); measurable vs non-measurable disease (1.31, 1.04-1.66); and no prior vs prior surgery (1.33, 1.16-1.53). Predictive factors for specific treatment comparisons based on ≥300 patients were: age (≥65 vs < 65); performance status; tumor location (GEJ vs stomach); disease stage; number of metastatic sites; peritoneal metastasis; measurable disease; histology; HER2; KRAS; VEGF A; and Neuropilin-1 for first line treatments; and time to progression on first line therapy ( < 3, 3-6 or ≥6 months) for second-line treatments. Conclusions: Eight independent prognostic factors for OS and thirteen clinically relevant predictive factors for treatment efficacy of EGC were found.