bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I/II trial of induction chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) followed by concurrent chemoradiotherapy in locally advanced esophageal squamous cell carcinoma.
Authors: Satake Hironaga , Tahara Makoto , Mochizuki Satoshi , Zenda Sadamoto , Kojima Takashi , Bando Hideaki , Yamazaki Tomoko , Kato Ken , Iwasa Satoru , Honma Yoshitaka , Hara Hiroki , Yokota Tomoya , Hamauchi Satoshi , Kiyota Naomi , Kii Takayuki , Chin Keisho , Ohtsu Atsushi 
Published: March 2020

4074 Background: Standard of care for unresectable locally advanced esophageal squamous cell carcinoma (ESCC) is concurrent chemoradiotherapy (CRT). However, its survival remains limited. Neoadjuvant chemotherapy with docetaxel, cisplatin and 5-FU (DCF) demonstrated promising activity with pathological complete response (CR) of 22% for resectable stage II/III ESCC (Hara H et.al, ASCO 2012). This study was performed to assess the efficacy and safety of induction chemotherapy with DCF followed by CRT in patients with unresectable locally advanced ESCC. Methods: Eligibility criteria included clinically T4 and/or M1 lymph node (LYM) ESCC, PS 0-1, and 20-70 years old. Treatment consisted of docetaxel 70 mg/m2, cisplatin 70 mg/m2 on day 1 and fluorouracil 750 mg/m2 on days 1 to 5, repeated every 3 weeks for three cycles, followed by cisplatin 70 mg/m2 on days 64 and 92, and fluorouracil 700 mg/m2on days 64 to 67 and 92 to 95 concurrently with radiotherapy (60Gy in 30 fractions, 5 days/week). Results: From August 2009 to November 2011, 33 patients were enrolled.There were 16 pts with T4M0 disease, 13 with nonT4M1 LYM, and 4 with T4M1 LYM.Most grade 3 or 4 toxicities were neutropenia (66%), leukopenia (39%), anorexia (18%), dysphasia (12%), nausea (9%), febrile neutropenia (6%), and hyponatremia (6%) during induction chemotherapy. Most grade 3 or 4 toxicities were leukopenia (27%), neutropenia (20%), dysphasia (17%), anorexia (13%), esophagitis (13%), nausea (10%), and febrile neutropenia (3%) during CRT. No treatment related death was observed. The completion rate of protocol treatment was 88% (29/33). The overall response rate after completion of induction chemotherapy was 61%. Eleven pts (38%) achieved CR after completion of protocol treatment. With a median follow-up period of 14 months, 1y-PFS and 1y-OS are 38.5 and 78.6 %, respectively. Of a total of 33 patients, eighteen patients (55%) received secondary treatment. Conclusions: Induction chemotherapy with DCF followed by CRT in unresectable locally advanced ESCC was well tolerated. Although these data are preliminay, this approach warrants further evaluation. Clinical trial information: UMIN000003370.
Interim safety analysis of a phase III trial with 5-FU, oxaliplatin, and docetaxel (FLOT) versus epirubicin, cisplatin, and 5-FU (ECF) in patients with locally advanced, resectable gastric/oesophagogastric junction (OGJ) cancer: The AIO-sto-0210 FLOT4 study.
Authors: Pauligk Claudia , Meiler Johannes , Hofheinz Ralf Dieter , Kopp Hans-Georg , Mayer Frank , Schmalenberg Harald , Luley Kim , Haag Georg Martin , Schmiegel Wolff H. , Homann Nils , Probst Stephan , Koenigsmann Michael , Prasnikar Nicole , Trojan Jorg , Egger Matthias , Mahlberg Rolf , Heike Michael , Tannapfel Andrea , Jäger Elke , Al-Batran Salah-Eddin 
Published: March 2020

4079 Background: Perioperative ECF is a standard treatment for localized gastric/OGJ adenocarcinoma. However, 5-year survival rate remains below 40%. The FLOT regimen is an effective combination with pathologic response rates in the 15% range. This phase III study compares both regimens in resectable stages. Methods: Pts are stratified by different baseline criteria and randomized to either 3 + 3 perioperative cycles of ECF (epirubicin 50 mg/m2, d1; cisplatin 60 mg/m², d1; 5-FU 200 mg/m², d1-d21, qd21) or 4 + 4 cycles of perioperative FLOT (docetaxel 50mg/m2, d1; 5-FU 2600 mg/m², d1; leucovorin 200 mg/m², d1; oxaliplatin 85 mg/m², d1, qd14). 5-FU can be replaced by capecitabine in the ECF-arm (ECX). Central pathology is performed. This is a preplanned safety analysis after 300 patients. Results: The ongoing studyhas enrolled 380 of planned 590 pts, so far. 305 pts were included in this analysis. Median age is 62 yrs; 78% of pts are male. The primaries were gastric in 44.9%, OGJ in 50.4% and not evaluable/documented in 4.7% of pts. 281 pts were eligible for safety analyses. Median no. of preoperative cycles was 3 and 4 with ECF/ECX and FLOT, respectively, 35.9% vs. 44.6% of pts (ECF/ECX vs. FLOT) started postoperative chemotherapy (ct) and 22.5% vs 33.1% received all planned cycles. Grade 3/4 neutropenia was observed in 28.0% of ECF/ECX and 45.3% of FLOT pts (p=.0026). Thromboembolic events occurred in 14.1% vs. 5.8% in pts with ECF/ECX vs. FLOT (p=.027). Serious adverse events occurred in 52.1% vs. 47.5% of pts with ECF/ECX vs. FLOT (p=.48). Preoperative delay/interruptions of ct were observed in 71.1% vs. 56.8% of pts with ECF/ECX vs. FLOT (p=.013). Dose modifications of preoperative ct were performed in 27.5% vs. 20.1% of treatment cycles with ECF/ECX vs. FLOT, respectively. 197 pts have undergone surgery so far. Severe surgical morbidity was similar in both arms (ECF/ECX, 19.8%; FLOT, 16.8%). Surgical mortality was observed in 4 and 2 pts with ECF/ECX and FLOT. Toxic deaths were observed in 1 pt each. Conclusions: Perioperative FLOT is feasible and safe. Clinical trial information: NCT01216644.
Final results of AGITG ATTAX3 study: Randomized phase II study of weekly docetaxel (T), cisplatin, and fluoropyrimidine (F) with or without panitumumab (P) in advanced esophagogastric (OG) cancer.
Authors: Tebbutt Niall C. , Price Timothy Jay , Sjoquist Katrin Marie , Veillard Anne-Sophie , Hall Merryn , Ferraro Danielle Angela , Wong Nicole , Pavlakis Nick , Strickland Andrew , Varma Suresh Chandra , Cooray Prasad , Young Rosemary , Underhill Craig , Shannon Jennifer Anne , Ganju Vinod , Gebski Val ,   Australasian GI Trials Group
Published: March 2020

4081 Background: This randomized phase II study evaluated the efficacy and safety of P, a fully human mAb against the epidermal growth factor receptor combined with T-based chemotherapy in advanced OG cancer. Methods: Eligible pts had histologically confirmed metastatic OG cancer (adeno-carcinoma and squamous cell carcinoma) were ≥18 years of age, PS 0-2, with adequate renal, haematologic and liver function with measurable disease. All pts provided informed consent. Selection was not based on kras determination. Pts received T 30mg/m2 d1,8, C 60mg/m2 d1 and F; investigator choice of 5FU infusion 160mg/m2/d or capecitabine 500mg/m2bd continuous ±P 9 mg/kg d1 q3w. Treatment was administered for 8 cycles or until PD. The primary endpoint was response rate according to RECIST (1.1) assessed q6w. Planned enrolment target was 100 pts. Stratification variables included histology, PS and choice of F. Results: From April 2010 to November 2011, 77 pts were enrolled from 15 institutions. A safety alert from the REAL3 study (also involving P in OG cancer) prompted an unplanned review of data from ATTAX3 by the IDMC. The IDMC found no evidence of adverse outcomes associated with P, but as it did not appear that P would significantly improve efficacy, they recommended cessation of the study to new enrolment. Previously enrolled pts were treated and followed according to protocol. Median follow up is 24m. Treatment arms were well balanced; median age 59, 64y, male 77%, 87%, PS0-1 95%,90%, adenocarcinoma 90%,90%, capecitabine 67%, 66% for TCF/TCF-P, respectively. Common grade 3/4 toxicities include infection 18%,24%, febrile neutropenia 10%, 5%, anorexia 10%, 24%, nausea 18%,30%, stomatitis 3%,5%, diarrhoea 15%,24% , acneiform rash 0%, 8%, fatigue 18%, 30%, hypomagnesemia 10%, 16% for TCF/TCF-P. Efficacy outcomes are summarized in Table. Conclusions: The addition of P to T-based chemotherapy in advanced OG cancer did not improve efficacy and was associated with an increase in some toxicities. Clinical trial information: ACTRN12609000109202. [Table: see text]
Pattern of local-regional relapse and survival after bimodality therapy for esophageal cancer: Implications for the surveillance strategy.
Authors: Sudo Kazuki , Xiao Lianchun , Wadhwa Roopma , Taketa Takashi , Blum Mariela A. , Skinner Heath D. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Komaki Ritsuko , Rice David C. , Swisher Stephen , Hofstetter Wayne Lewis , Ajani Jaffer A. 
Published: March 2020

4083 Background: Evidence for definitive chemoradiotherapy (bimodality therapy [BMT]) has been established for patients with esophageal and gastroesophageal junction cancer (EGEJC) who do not qualify for surgery. Surveillance for these patients is often recommended but the literature lacks guidance for an evidence-based surveillance strategy after BMT. Methods: We analyzed 276 patients with EGEJC who underwent BMT and had pre- and postchemoradiation endoscopic biopsies and imaging studies available for review. Patients who underwent planned surgery or salvage surgery (SS) within 6 months from BMT were excluded. We reviewed the pattern of relapse over time. Local-regional disease (LRD) after BMT was classified as regional disease (RD) or luminal-only disease (LD). Overall survival (OS) probabilities were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: For 276 patients, the median follow-up time was 53.0 months (95% confidence interval [CI], 47.3-58.7). A total of 184 (66.7%) patients had a persistent disease or relapse after BMT: 120 distant metastases (43.5% of 276) and 64 LRD (23.2% of 276). Of 64 LRD, 58 (91%) were diagnosed within 2 years of BMT and 63 (98%) were diagnosed within 3 years (see Table). Twenty-three of 64 LRD patients underwent SS. For patients with SS, the median OS time from diagnosis of LRD was 58.0 months (95% CI, not reached), and that for patients without SS was 9.0 months (95% CI, 7.3-10.7); this difference was highly significant (p < 0.001). Conclusions: Our data suggest that 91% of LRD occurred within 2 years after BMT and the OS with SS for LRD was better than that without SS. These data can contribute to the development of an evidence-based surveillance strategy. [Table: see text]
Phase II study of mFOLFOX with bevacizumab (Bev) in metastatic gastroesophageal and gastric (GE) adenocarcinoma (AC).
Authors: Li Jia , Kortmansky Jeremy S. , Fischbach Neal A. , Stein Stacey , Yao Xiaopan , Hochster Howard S. , Lacy Jill 
Published: March 2020

4084 Background: The median survival for patients (pts) with metastatic GE AC in phase III studies is <12 mos. Bev has demonstrated promising activity in metastatic GE AC when used in combination with cisplatin-based regimens in studies with patients from the Americas. We conducted a prospective phase II trial to investigate the efficacy of Bev in combination with mFOLFOX6 in pts with metastatic GE AC. Methods: Pts with previously untreated metastatic GE AC (gastric, GE junction, distal esophagus) received mFOLFOX6 (LV 400 mg/m2, 5-FU 400 mg/m2 bolus and 2400 mg/m2 over 46 hr continuous infusion, Ox 85 mg/m2) and Bev 10 mg/kg q 2 wks. Response by RECIST was evaluated by CT q 8 wks. Primary objective was time to progression (TTP); secondary objectives were safety, response rate (RR), and overall survival (OS). Results: 39 pts were enrolled between 09/08 and 06/12. Pt characteristics are as follows: median age, 59 yo (range 27-79); M/F, 31/8; ECOG PS 0/1, 11/28; gastric/distal E and GEJ, 13/26; metastatic sites: lymph nodes 23, liver 19, lung 9, peritoneum 9; >2 metastatic sites, 20; prior gastrectomy or esophagectomy, 7. Nine pts remain on study, and 15 pts are alive. Median # of cycles administered is 11 (range 4 - >31). RR is 56.4% (4 CR, 18 PR). Median TTP is 8.2 mos. Median OS is 15.2 mos. Three pts survived >24 mos. Grade 3/4 toxicities include neutropenia (13, 33.3%), neuropathy (8, 20.5%), DVT/PE (5, 12.8%), thrombocytopenia (3, 7.7%), anemia (1, 2.6%), hypertension (1, 2.6%), and proteinuria (1, 2.6%). We observed no GI perforations or grade 3/4 GI hemorrhagic events. Conclusions: FOLFOX6/Bev is well tolerated and associated with increased TTP and OS in pts with metastatic GE AC compared to historical data from similar populations treated without Bev. Our findings validate previous studies with Bev in combination with cisplatin-based regimens in pts from the Americas with metastatic GE AC. This study is supported by Genentech. Clinical trial information: NCT00673673.
FOLFIRI plus sunitinib versus FOLFIRI alone in advanced chemorefractory esophagogastric cancer patients: A randomized placebo-controlled multicentric AIO phase II trial.
Authors: Moehler Markus Hermann , Thuss-Patience Peter C. , Schmoll Hans-Joachim , Hegewisch-Becker Susanna , Wilke Hansjochen , Al-Batran Salah-Eddin , Weissinger Florian , Kullmann Frank , Von Weikersthal Ludwig Fischer , Siveke Jens T. , Kanzler Stephan , Schimanski Carl Christoph , Otte Melanie , Schollenberger Lukas , Koenig Jochem , Galle Peter Robert 
Published: March 2020

4086 Background: Sunitinib is an receptor tyrosine kinase (RTK) inhibitor of VEGFR1-3, PDGFR-α-β, and other RTK. After we established Sunitinib (Sun) alone associated with limited response rate (RR) and good tolerability in refractory advanced esophagogastric cancer patients (Moehler et al. EUR J Cancer. 2011, 47: 1511), this double-blinded placebo-controlled phase II evaluated safety and efficacy of SUN as add-on in second-line or third-line FOLFIRI (ClinicalTrials.gov NCT01020630). Methods: Patients with failure of any prior docetaxel and/or platinum-based chemotherapy were randomized to receive 6-week cycles including FOLFIRI two weekly and SUN (25 mg) versus (vs) placebo (PLA) daily for 4 consecutive weeks followed by a 2-week rest. Primary endpoint was progression-free survival (PFS). Results: 91 randomized patients (ITT) had similar characteristics in both groups (SUN/PLA 45/46). Both groups had 2.7 treatment cycles. Objective RR was 20/29%, and tumor control rate was 58/56 % for SUN/PLA, respectively. Median PFS was similar for SUN vs. PLA with 3.6 vs. 3.3 months, respectively (HR 1.11; 95%CI 0.70-1.74, P = 0.66). Median overall survival (OS) was longer for SUN vs. PLA with 10.5 vs. 9.0 months, in ITT (HR 0.816; 95%CI 0.50 - 1.34, P = 0.42, one-sided 0.21) and in the per protocol population (HR 0.71; 95%CI 0.41 - 1.24, P = 0.23) respectively. No unexpected higher toxicities, SAE or SUSAR occurred with SUN. For SUN/PLA, all grade AEs (%) possibly related to study drug were nausea 49/47%, fatigue 36/29%, vomiting 27/29%, diarrhoea 36/38%, neutropenia 62/22%, stomatitis 27/20%, and palmar-plantar erythrodysaesthesia 13/3%, and Grade 3+ AEs (%) were neutropenia 56/20%, diarrhoea 2/13%, nausea 7/7%, fatigue 0/9% and pain 0/9%, respectively. Performed quality of life outcomes were mostly in favor of Sunitinib. Conclusions: In our phase II trial, Sunitinib added to FOLFIRI increased hematotoxicity and did not improve response rates or PFS in chemotherapy-resistant GC patients. Since the regimen was safe and patients had a trend to better OS, biomarker analyses will be performed to identify subgroups that benefit from add-on Sunitinib. Clinical trial information: NCT01020630.
Who benefits from radiotherapy for gastric cancer? A meta-analysis.
Authors: Ohri Nitin , Garg Madhur , Aparo Santiago , Kaubisch Andreas , Tome Wolfgang A. , Kennedy Timothy J. , Kalnicki Shalom , Guha Chandan 
Published: March 2020

4093 Background: Randomized trials have demonstrated significant survival benefits with the use of adjuvant (including neoadjuvant) chemotherapy or chemoradiotherapy for gastric cancer. The importance of adjuvant radiotherapy (RT) remains unclear. Here we perform an up-to-date meta-analysis of randomized trials testing the use of radiotherapy for resectable gastric cancer. Methods: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials for randomized trials testing adjuvant RT for resectable gastric cancer. Hazard ratios describing the impact of adjuvant RT on overall survival (OS) and disease-free survival (DFS) were extracted directly from the original studies or calculated from survival curves. Pooled estimates were obtained using the inverse variance method. Subgroup analyses were performed to determine if the efficacy of RT varies with chemotherapy use, RT timing, geographic region, type of nodal dissection performed, and lymph node status. Results: Thirteen studies met all inclusion criteria and were used for this analysis. Adjuvant RT was associated with a significant improvement in both OS (HR=0.78, 95% CI: 0.70 to 0.86, p<0.001) and DFS (HR=0.71, 95% CI: 0.63 to 0.80, p<0.001). In the five studies that tested adjuvant chemoradiotherapy against adjuvant chemotherapy, similar effects were seen for OS (HR=0.83, 95% CI: 0.67 to 1.03, p=0.087) and DFS (HR=0.77, 95% CI: 0.91 to 0.65, p=0.002). Available data did not reveal any subgroup of patients that does not benefit from adjuvant RT. Conclusions: In randomized trials for resectable gastric cancer, adjuvant RT provides an approximately 20% improvement in both DFS and OS. Available data do not reveal a subgroup of patients that does not benefit from adjuvant RT. Further study is required to optimize the implementation of adjuvant RT for gastric cancer with regards to patient selection and integration with systemic therapy.
Nomogram predicting long-term survival probability of thoracic esophageal squamous cell carcinoma after radical esophagectomy.
Authors: Mao Weimin , Zhou Xinming , Chen Qixun , Jiang Youhua , Yang Xun , Wu Jie , Tao Kaiyi , Zheng Weihui , Yan Zhen , Liu Liang , Wu Shaoyuan , Su Dan 
Published: March 2020

4094 Background: Nomograms have been widely and successfully used for numerous cancers to obtain reliable prognostic information for each individual patient.To date, however, no studies have conducted survival estimates using nomograms for esophageal squamous-cell carcinoma (ESCC) in Chinese population.The purpose of this study is to develop a nomogram to predict the long-term survival probabilities in patients diagnosed with ESCC after radical esophagectomy. Methods: This study involves a dataset containing 1923 patients who underwent radical esophagectomy for ESCC at Zhejiang Cancer Hospital in Hangzhou, China. Among them, 1,578 patients with no missing data were used to build a prognostic nomogram based on Cox proportional hazard regression model. A multivariate survival analysis using Cox regression model was applied to identify significant variables with P-values <0.05. On the basis of the predictive model with the identified variables, a nomogram was constructed for predicting five-year and ten-year overall survival probabilities. The prediction model was internally validated using bootstrap resampling, assessing its optimism-corrected discrimination and calibration. Results: The median of overall survival times of 1578 ESCC patients was 35.6 months, and the 5-year and 10-year survival rate was 32% and 20%, respectively. The multivariate Cox model identified alcohol, tumor length, surgical approach, number of surgical removed lymph node, ratio of metastatic lymph nodes, region of lymph nodes dissection, depth of invasion, differentiation of tumor, postoperative complications as covariates significantly associated with survival. Across the 100 bootstrap replicates, the median optimism-corrected summary C-index for predicting survival was 0.713 (SE=0.011). Conclusions: A nomogram predicting 5- and 10-year overall survival after radical esophagectomy for ESCC in Chinese population was constructed and validated based on nine significant variables. The nomogram can be applied in daily clinical practice for individualized survival prediction of ESCC patients after potentially curative esophagectomy.
Result of clinical study on feasibility of laparoscopy-assisted D2 distal gastrectomy to treat advanced gastric cancer (COACT_1001).
Authors: Kim Young Woo , Park Young-Kyu , Yoon Hong Man , Nam Byung-Ho , Ryu Keun Won , Lee Young-Joon , Jeong Oh , Yoon Ki Young , Lee Jun Ho , Lee Sang Eog , Yu Wansik , Jeong Sang-Ho , Kim Taebong 
Published: March 2020

4105 Background: Benefit of quality of life made laparoscopic gastric cancer surgery attractive, but there are still concerns about laparoscopic lymph node dissection. The aim of this study was to evaluate a feasibility of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection compared with open distal gastrectomy (ODG) for advanced gastric cancer (AGC). Methods: Patients with cT2-T4a and cN0-2 (AJCC 7th staging system) distal gastric cancer were randomly assigned to LADG or ODG. The primary endpoint was the non-compliance rate of the lymph node dissection defined as rate of cases where there was more than one missing lymph node station according to the guidelines of the Japanese Research Society for Gastric Cancer lymph node grouping. Secondary endpoints were perioperative complications, changes of inflammatory and immunological parameters, postoperative hospital stay, and 3 year disease free survival. This trial was registered at ClinicalTrials.gov as NCT01088204. Results: Between Jun 2010 and Oct 2011,204 patients were randomly allocated and underwent either LADG (n=105) or ODG (n=99). 8 patients were excluded in the intention to treatment analysis because of protocol violation and patient’s withdrawal of permission, and finally 100 patients in LADG and 95 patients in ODG were analyzed. There were no significant differences of overall non-compliance rate of lymph node dissection between LADG and ODG groups; they were respectively 47.0% and 43.2%. (p=0.648). In the subgroup analysis according to the stratified risk groups, non-compliance rate in LADG was significantly higher than ODG (52.0% vs. 25.0%, p=0.043) for clinical stage III but it was not significantly different for stage II (46.2% vs. 48.9%, p=0.788). Intraoperative event rate was not significantly different between groups (LADG;6.0% and ODG;4.2%, p =0.748). Complications rate in early postoperative period up to 1 month was also not different between groups (LADG;17.0 %, ODG;18.8%, p=0.749). Conclusions: LADG was feasible in AGC compared with ODG, especially in clinical stage II in terms of non-compliance rate of D2 lymph node dissection and perioperative complications. Clinical trial information: NCT01088204.