bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II study of neoadjuvant chemotherapy with modified FOLFOXIRI in borderline resectable or unresectable stage III pancreatic cancer.
Authors: Vasile Enrico , De Lio Nelide , Cappelli Carla , Pollina Luca , Funel Niccola , Sainato Aldo , Ginocchi Laura , Lucchesi Maurizio , Caparello Chiara , Caponi Sara , Perrone Vittorio , Pasqualetti Francesco , Caniglia Fabio , Signori Stefano , Mazzeo Salvatore , Greco Carlo , Falcone Alfredo , Campani Daniela , Mosca Franco , Boggi Ugo 
Published: March 2020

4062 Background: FOLFIRINOX has shown high activity in metastatic pancreatic cancer (PC) patients and could be an interesting regimen also for patients with inoperable locally advanced disease. Our group had developed a similar schedule in metastatic colorectal cancer named FOLFOXIRI with good tolerance and activity. Therefore, we have decided to perform a phase II trial to prospectively evaluate the activity of modified FOLFOXIRI in borderline resectable or unresectable PC. Methods: Modified FOLFOXIRI consisted of a lower dose of irinotecan (150 mg/sqm) and of infusional 5-fluorouracil (2800 mg/sqm as a 48-hour continuous infusion on days 1 to 3) with no bolus 5-fluorouracil. Folinic acid and oxaliplatin (85 mg/sqm) remained unchanged. The study enrolled patients with diagnosis of pancreatic adenocarcinoma, stage III borderline resectable or unresectable disease (cT4,cN0-1,cM0), ECOG PS 0-1, age 18-75. The primary end-point of the study was the percent of patients who undergo radical surgical resection after chemotherapy. Results: Thirty-two patients have been enrolled; M/F=12/20; PS 0/1=16/16. Median age was 60 years (range 44-75). Median number of FOLFOXIRI cycles was 6 (range 2-14). Grade 3-4 toxicities was experienced by 20 patients during chemotherapy. Twelve partial responses (37%) and 14 stable diseases (45%) have been observed; 2 patients had progressive diseases (6%). The remaining 4 patients (12%) have not been yet evaluated because are still in the first months of treatment. A local treatment was received after chemotherapy by 18 patients until now: 13 (41%) received radical surgical resection and 5 received concomitant chemo-radiotherapy. Three explorative laparotomy showed occult metastases. In other 7 cases surgery is planned while 2 patients refused surgery. Median progression-free survival is 14.0 months and median overall survival is 24.2 months with a two-year survival rate of 54%. Conclusions: Chemotherapy with FOLFOXIRI seems active in locally advanced PC and may allow to obtain a downstaging of disease leading to achieve a curative surgical resection in some cases. Longer follow up is needed to better evaluate long-term outcome of this strategy.
The effect of anti-IGF1 therapy on muscle mass in metastatic pancreatic cancer.
Authors: Fogelman David R. , Khalil Mohamed Aly , Hassan Manal , Garg Naveen , Javle Milind M. , Katz Matthew H. G. , Holmes Holly Michelle , Abbruzzese James L. 
Published: March 2020

4064 Background: IGF-1 plays a role in the growth of multiple tumor types, including pancreatic cancer. IGF-1 also serves as a growth factor for muscle. The impact of therapeutic targeting of IGF-1 on muscle mass is unknown. Methods: We evaluated muscle mass at L3 in patients enrolled in a randomized phase II study of MK-0646 (M), a monoclonal antibody directed against the IGF-1 protein, in patients with metastatic pancreatic cancer (MPC). We used the Slice-o-matic (ver 4.3) software to segregate CT images into muscle and fat components and measured muscle area (cm2) at baseline and after 2 and 4 months of treatment. Patients received either gemcitabine with erlotinib (G+E), G+E+M, or G+M. Differences between the groups were compared using t-tests. Results: 58 patients had both baseline and 2 month imaging available for analysis. Of these, 44 received M and 14 had G+E only. Baseline muscle mass between the two groups was similar: 146 cm2 and 142 cm2, respectively (P=0.47). After two months of treatment, both groups demonstrated decrease in muscle mass: 134 cm2 (8% loss) vs. 130 cm2 (6% loss) (P= 0.19). Of the 37 patients who had either PR or SD at 2 months, there was a non-significant increase in muscle mass loss among the patients receiving M (7.8% vs. 4.5%, p=.31). At 4 months, those remaining patients in the M group lost 6% (n=14) of muscle mass compared to 3% in the non-M group (n=5) (P=0.54). Each 1% loss of muscle mass increased the odds of dropout by 13% (p=.03, CI 1.0-27%) and predicted for poor survival (p=HR 1.08, p=.02). Conclusions: MPC patients can be expected to lose muscle mass even while having clinical benefit (PR or SD) from chemotherapy. Muscle loss correlated with a risk of study drop-out and death. There was a non-significant trend towards greater muscle mass loss in patients on anti-IGF-1R therapy. However, it is unclear if this loss translates into functional differences between patients. Clinical trial information: NCT00769483.
Prognostic implications of signet ring cell histology in esophageal adenocarcinoma: A SEER database analysis
Authors: Yendamuri Saikrishna S. , Huang Miriam , Malhotra Usha , Warren Graham Walter , Bogner Paul , Nwogu Chukwumere E. , Groman Adrienne , Demmy Todd L. 
Published: March 2020

4067 Background: Signet ring cell esophageal adenocarcinoma histology has been difficult to study in a single institution series because of its relative rarity, yet has an anecdotal reputation for poor prognosis. We examined the Surveillance Epidemiology and End Results (SEER) database to assess the prognostic implications of this esophageal adenocarcinoma subtype. Methods: All patients with esophageal adenocarcinoma in the SEER database from 2004 – 2009 were included. Characteristics of patients with signet ring cell histology were compared to those without it. Univariate and multivariate analyses examining the relationship of signet ring cell histology with overall survival (censored at 72 months) were performed in all patients, as well as those undergoing surgical resection. Results: 597 of 11,838 (5%) study patients had signet ring cell histology. Patients with signet ring cell histology were similar in age, race, and gender distribution, but had a higher grade (p<0.001) and higher stage (p<0.001) at diagnosis. In both all-comers as well as those undergoing surgical resection, univariate analyses showed a worse survival in patients with signet ring cell esophageal cancer (HR = 1.24; 95% CI 1.13-1.37 and HR = 1.57; 95% CI 1.29-1.92 respectively). In multivariate analyses adjusting for age, gender, grade, stage, and race, patients with signet ring cell cancer had a worse prognosis than those with non-signet ring cell adenocarcinoma (HR = 1.20; 95% CI 1.09 -1.33). In surgically resected patients, this remained a trend, but did not reach statistical significance (HR = 1.16; 95% CI 0.94-1.42). Conclusions: This large study of esophageal adenocarcinoma confirms the clinical impression that signet ring cell variant of adenocarcinoma is associated with an advanced stage at presentation and a worse prognosis independent of stage of presentation.
Nomogram for predicting the benefit of neoadjuvant chemoradiotherapy for esophageal cancer: A SEER-Medicare analysis.
Authors: Eil Robert , Diggs Brian S. , Wang Samuel J. , Dolan James P. , Hunter John G. , Thomas Charles R. 
Published: March 2020

4073 Background: The impact of neoadjuvant chemoradiotherapy for esophageal cancer remains difficult to establish for specific patient (pt) populations. The primary aim of this study was to create a web-based prediction tool that provides individualized survival projections based on clinically relevant tumor and treatment data. Methods: Pts diagnosed with esophageal cancer between 1997 and 2005 were selected from the Surveillance, Epidemiology, and End Results (SEER) Medicare database. The covariates chosen for retrospective analysis were: sex, T and N stage, histology, total lymph nodes examined, and receipt of neoadjuvant chemotherapy (CT), radiotherapy (RT), or chemoradiotherapy (CRT). After weighting correction by treatment groups, a log logistic regression model for overall survival (OS) was selected based on goodness of fit analysis. Based on bootstrap resampling with 100 repetitions the Concordance Index (CI) was 0.703. Results: 1,128 resected esophageal pts that either did or did not receive neoadjuvant treatment were appropriate for analysis. On log logistic multivariate analysis: age, sex, T stage, N stage, number of lymph nodes harvested, receipt of neoadjuvant CRT, and receipt of chemotherapy were significantly associated with OS. All T stages greater than 1 benefitted from neoadjuvant CRT (p=<0.001). No T stage benefitted from isolated neoadjuvant CT or RT. Patients with nodal metastases benefitted from neoadjuvant CRT (p=<0.001) and CT (p=0.002). Conclusions: SEER-Medicare pts with resected esophageal cancer can be used to produce a survival prediction tool that can: 1) serve as a counseling and decision aid to pts and caregivers regarding their postoperative prognosis and 2) assist in research protocol design. Patients T2 or greater or with lymph node metastases benefitted from neoadjuvant CRT based on our data. This nomogram may underestimate the benefit of neoadjuvant CRT due to its variable downstaging effect on final pathologic stage. This web based tool is available for use at http://skynet.ohsu.edu/nomograms .
Safety, tolerability, and efficacy of the first-in-class antibody IMAB362 targeting claudin 18.2 in patients with metastatic gastroesophageal adenocarcinomas.
Authors: Schuler Martin H. , Zvirbule Zanete , Lordick Florian , Krilova Anna , Helbig Ulrike , Schulze-Bergkamen Henning , Thuss-Patience Peter C. , von Wichert Goetz , Schulmann Karsten , Trarbach Tanja , Bauer Stefan , Mueller Christian , Al-Batran Salah-Eddin , Huber Christoph , Sahin Ugur , Tureci Oezlem 
Published: March 2020

4080 Background: IMAB362 is a monoclonal antibody targeting isoform 2 of the tight junction component claudin 18 (CLDN18.2), a tumor-selective antigen frequently expressed in several types of epithelial adenocarcinomas. Preclinically, IMAB362 exerts its antitumor activity by ADCC, CDC, induction of apoptosis and inhibition of cell proliferation. Methods: Patients with treatment-refractory, metastatic gastroesophageal adenocarcinomas with CLDN18.2-positive tumors as determined by immunohistochemistry were enrolled in two clinical trials of IMAB362 monotherapy. A phase I inter-patient single dose escalation study (n=15, 5 dose groups from 33 mg/m² to 1000 mg/m² with 3 patients each, follow-up 4 weeks) was conducted followed by a phase II study (n=34, 300 mg/m2 [n=4] and 600 mg/m2[n=30]) administered every two weeks for 5 courses, imaging in week 11. Patients with disease control allowed to continue IMAB362 therapy until progression. Analysis of the phase II trial is ongoing. Results: In the phase I trial, all dose levels of IMAB362 were generally well tolerated. Nausea and vomiting were the most common adverse events (AEs). No dose limiting toxicity was observed at single doses up to 1,000 mg/m². Based on pharmacokinetic considerations and preclinical dose/response data, the recommended doses for the phase II multidose trial was 600 mg/m². In the phase II study, 34 patients were evaluable for safety. No grade 4 AEs occurred, grade 3 AEs were vomiting (n=8, 24%), nausea (n=4, 12%) and hypersensitivity (n=1, 3%). As of January 2013, 31 patients were evaluable for efficacy analysis. Four patients had achieved a confirmed partial response, and eight patients had disease stabilization (ORR=13%, DCR=39%). The longest observed response duration thus far was 40 weeks. Conclusions: IMAB362 antibody therapy of patients with advanced CLDN18.2-positive gastroesophageal adenocarcinomas is safe and well tolerated. Early evidence for antitumoral activity was observed in the phase II trial. Further clinical evaluation of IMAB362 in patients with CLDN18.2 tumors is warranted. Clinical trial information: NCT01197885.
NeoHx study: Perioperative treatment with trastuzumab in combination with capecitabine and oxaliplatin (XELOX-T) in patients with HER2 resectable stomach or esophagogastric junction (EGJ) adenocarcinoma—R0 resection, pCR, and toxicity analysis.
Authors: Rivera Fernando , Jiménez Paula , Garcia Alfonso Pilar , Lopez Carlos , Gallego Javier , Limon M. Luisa , Alsina Maria , Lopez-Gomez Luis , Galán Maica , Falco Esther , Manzano Jose Luis , González Encarnación , Serrano Raquel , Fernandez Parra Eva , Jorge Monica 
Published: March 2020

4098 Background: Perioperative chemotherapy has demonstrated better OS and DFS than surgery alone in resectable stomach or EGJ adenocarcinoma. Trastuzumab has improved OS when added to chemotherapy in pts with HER-2 + metastatic gastric cancer and is interesting to explore its role in the perioperative setting. Methods: A Spanish, multicenter, open-label phase II study evaluated the efficacy and toxicity profile of perioperative XELOX-T (capecitabine 1000 mg/m2/12h po days 1-14, oxaliplatin 130 mg/m2 day 1, trastuzumab 8 mg/kg→ mg/kg day 1, q3w ; 3 preoperative cycles and 3 postsurgery cycles followed by 12 cycles of trastuzumab monotherapy) in patients with T1-2N+M0 or T3-4NxM0 resectable stomach or EGJ adenocarcinoma, HER-2+ ( IHQ3+ or IHQ2+/FISH+). The primary endpoint was 18 months DFS, secondary endpoint included pCR, R0 resection rate, ORR and toxicity of preoperative treatment (NCI CTC v3.0 criteria). Results: From June 2010 to March 2012, 36 pts were included: median age 65 (39-85); ECOG 0/1/2: 16/19/1 pts; localization: stomach 21 pts, EGJ 15 pts; histologic type: intestinal: 23 pts, diffuse: 4 pts, mixed: 1pt, not specified 8 pts; TNM: T 4: 7 pts; N+: 31 pts. Preoperative XELOX-T: Response: PR: 14 pts (39%), SD: 18 pts, PD: 0 pts, NE: 4 pts. G-3-4 toxicity (≥ 5% of pts): diarrhea 22% and asthenia 5%. Surgery was performed in 31 pts: R0: 28 pts (78%, 95% CI: 61-90%), R1: 1 pt, R2: 2 pts (1 had peritoneal carcinomatosis); pCR was observed in 7 pts (19 %; 95% CI: 8-36%) and 22 pts (61%) were pN0. Two pts died due to surgical complications,. We do not have mature data about postoperative XELOX-T yet. Follow-up is still too short for DFS and OS. Conclusions: This preliminary analysis suggests that perioperative XELOX+T in HER-2 positive resectable stomach or esophagogastric junction adenocarcinoma is feasible and has interesting activity. Clinical trial information: NCT01130337.
Determination of the optimal cutoff percentage of residual tumors to define the pathologic response rate (pathRR) of gastric cancer (GC) treated with preoperative therapy (JCOG1004-A).
Authors: Nakamura Kenichi , Kuwata Takeshi , Shimoda Tadakazu , Mizusawa Junki , Katayama Hiroshi , Kushima Ryoji , Taniguchi Hirokazu , Katai Hitoshi , Yoshikawa Takaki , Yabusaki Hiroshi , Kawashima Yoshiyuki , Kawabata Ryohei , Fukushima Norimasa , Iwasaki Yoshiaki , Tsuburaya Akira , Kinoshita Taira , Sano Takeshi , Sasako Mitsuru , Fukuda Haruhiko 
Published: March 2020

4104 Background: PathRR is a common endpoint used to assess the efficacy of preoperative therapy for GC. PathRR is estimated based on the percentage of the residual tumor area in the preexisting tumor bed. Various cut-off definitions that have used for past studies (e.g. 10%, 33%, 40%, 50%, 67%) often impair the comparability of pathRRs between studies. Methods: Individual patient data from four JCOG trials evaluating preoperative chemotherapy were used (JCOG0001, irinotecan+cisplatin, n=55; JCOG0002, S-1, n=55; JCOG0210, S-1+cisplatin, n=50; JCOG0405, S-1+cisplatin, n=53). Pathological specimens were evaluated from 173 out of 188 patients (92%) who underwent surgery. Residual and preexisting tumor areas were traced on a virtual microscopic slide by one pathologist and another confirmed these areas. The hazard ratio (HR) in overall survival was calculated for each cut-off percentage by stratified Cox regression analysis including the study as a stratification factor, and concordance probability estimates (CPE) were also calculated. Results: The numbers of patients with 0-10%/11-33%/34-50%/51-66%/67-100% residual tumors were 43/33/27/23/47, respectively. Overall, HR was the largest in the 10% cut-off and CPE was the largest in 33%. When patients with R1/R2 resections were excluded, both HR and CPE were the largest in the 10% cut-off. In subgroup analyses, almost all cut-offs predicted survival well regardless of the histologic type (intestinal/diffuse), and no cut-off predicted survival for type 4 (linitis plastica type) tumors. Conclusions: PathRR is not recommended for clinical trials including type 4 tumors. The 10% cut-off is recommended for non-type 4 tumors, though 33% is also applicable. [Table: see text]
The Chinese subgroup from a randomized phase III study of lapatinib in combination with weekly paclitaxel versus weekly paclitaxel alone as second-line treatment of HER2-amplified advanced gastric cancer (AGC) in Asian countries.
Authors: Sun Guo-ping , Sun Yan , Xu Rui-hua , Xu Jian-Ming , Li Jin , Wang Jin-Wan , Qin Shukui , Feng Ji Feng , Ba Yi , Shen Lin , Bai Yu-Xian , Sun Yihong , Pan Hongming , Cheng Ying , Yu Shiying , Zhong Haijun , Bai Li , Luo Rongcheng , Kobayashi Mikiro , Ohtsu Atsushi 
Published: March 2020

4109 Background: TyTAN is a randomized phase III study to evaluate lapatinib (L) plus paclitaxel (P) in pretreated HER2 amplified (HER2+) advanced gastric cancer (AGC). The disease characteristics and GC treatment pattern differed in Japan and in China, so a subgroup analysis was done for subjects recruited in mainland China. Methods: AGC subjects with prior 5-FU and/or cisplatin and HER2 amplification by fluorescence in situ hybridization (FISH) in tumor tissue were randomized 1:1 to L (1500mg QD) and P (80mg/m2, Day 1, 8, 15 q4w) or P alone (80mg/m2, Day 1, 8, 15 q4w). 1st endpoint was overall survival (OS). 2nd endpoints included progression free survival (PFS), overall response rate (ORR) and safety. A total of 95 subjects recruited from mainland China. Results: TyTAN was not significant in OS (HR0.84), but 2 months OS improvement was observed in L+P arm. The results from Chinese subgroup are shown in the Table. The most common adverse events in Chinese subjects were similar as in whole population (neutropenia, diarrhea, rash, leukopenia, anemia, fatigue). Compare to the overall results, less Chinese subjects reported nausea and vomiting. Conclusions: This analysis showed that there were clear regional differences as observed between subjects in China and Japan. The addition of L to P was associated with a clinically meaningful benefit in subjects recruited from mainland China. These data warrants further prospective evaluations on the impact of regional differences in the outcome of HER+ GC in East Asian patients. Clinical trial information: NCT00486954. [Table: see text]
Hepatic arterial infusion for unresectable intrahepatic cholangiocarcinoma: An update on survival from two prospective clinical trials.
Authors: Konstantinidis Ioannis , Do Richard Kinh Gian , Gultekin David H. , Gonen Mithat , Schwartz Lawrence H. , Fong Yuman , Allen Peter J. , D'Angelica Michael Ian , DeMatteo Ronald P. , Klimstra David S. , Kemeny Nancy E. , Jarnagin William R. 
Published: March 2020

4116 Background: Patients with unresectable intrahepatic cholangiocarcinoma (IHC) experience poor survival. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (Dex) (with or without bevacizumab (Bev)) in advanced IHC. Methods: Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Disease response was based on RECIST. All patients underwent pre-treatment dynamic contrast enhanced MRI (DCE-MRI), and tumor perfusion data were correlated with outcome. Results: Forty-four patients were analyzed (FUDR=26, FUDR/Bev=18). At a median follow-up of 30 months, 41 patients had died of disease and 3 were alive. Partial response was observed in 48% of patients, and another 50% had stable disease. Three patients underwent resection after HAI and 84% received additional HAI after removal from the study. Median survival was similar in both trials (FUDR=29 months vs. FUDR/Bev=28.5 months p=0.96). Ten patients (23%) survived ≥3 years including 5 (11%) ≥ 5 years. Tumor perfusion, as measured on pre-treatment DCE-MRI (area under the gadolinium concentration curve (AUC180)), was significantly higher in ≥3-year survivors, and was the only factor that distinguished this group from <3-year survivors (mean AUC180 48.9mM.s vs 32.3mM.s, respectively; p=0.003). Time to liver progression was longer in ≥3-year survivors (19.8 months vs 11.2 months, respectively; p=0.02). Conclusions: HAI chemotherapy can result in prolonged survival in unresectable IHC. Pre-treatment DCE-MRI may predict response and survival. [Table: see text]
Cisplatin and gemcitabine for advanced biliary tract cancer: A meta-analysis of two randomized trials.
Authors: Mizuno Nobumasa , Valle Juan W. , Furuse Junji , Jitlal Mark , Beare Sandy , Wasan Harpreet , Bridgewater John A. , Okusaka Takuji 
Published: March 2020

4120 Background: Two recent randomised studies (ABC-02 [UK] and BT22 [Japan]) have demonstrated the superiority of cisplatin and gemcitabine (CisGem) chemotherapy over gemcitabine (Gem) alone for patients with pathologically-proven advanced biliary tract cancer (BTC: cholangiocarcinoma, gallbladder and ampullary cancers). Methods: We performed a meta-analysis of individual patient-level data of these studies to establish the effect of CisGem vs. Gem on progression-free survival (PFS), overall survival (OS) and performed exploratory sub-group analyses. Results: A total of 493 patients, median age 64 years (range 23-84 years) with approximately equal sex distribution, were randomised (ABC-02 study n=410; BT22 study n=83) to receive either CisGem (n=245) or Gem (n=248). CisGem demonstrates a significant improvement in PFS (hazard ratio (HR)=0.64 (95%-CI: 0.53-0.76), p<0.001) and OS (HR=0.65 (95%-CI: 0.54-0.78), p<0.001) over Gem. This effect is most marked in patients with good performance status (PS 0-1): HR for PFS is 0.61 (95%-CI: 0.51-0.74), p<0.001 and HR for OS is 0.64 (95%-CI: 0.53-0.77), p<0.001. CisGem resulted in improved PFS and OS for intra- and extra-hepatic cholangiocarcinomas and gallbladder cancer. The treatment effect between UK and Japanese patients was consistent with respect to OS (HR=0.65, 95%-CI 0.53–0.79 and 0.65, 95%-CI 0.42–1.03, respectively); with similar median survival in the combination arms (median 11.7 and 11.1 months, respectively). Subgroups least likely to benefit included patients with ampullary tumours and poor performance score (PS2). Conclusions: CisGem is the standard of care for the first-line treatment of good-PS patients with advanced BTC regardless of ethnicity. Future studies should aim to enhance the effectiveness of this regimen in the first-line setting and establish the role of subsequent (second-line) therapy. Clinical trial information: ABC-02: NCT00262769, BT22; NCT00380588.