bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant and adjuvant, floxuridine, leucovorin, oxaliplatin, and docetaxel (FLOD) in patients with locally advanced operable gastroesophageal adenocarcinoma: A phase II study with pathologic responses and long term follow-up.
Authors: Ardalan Bach , Gombosh Miriam , Franceschi Dido , Avisar Eli , Yakoub Danny , Ribeiro Afonso , Garrido Jose , Merchant Nipun , Livingstone Alan S 
Published: February 2017

124 Background: A complete pathological response to neoadjuvant chemotherapy without the use of radiation has infrequently been reported in operable chemo-naïve stage III gastro esophageal adenocarcinoma patients. Methods: Twenty-nine patients were enrolled in this study. Neoadjuvant therapy consisted of Floxuridine, Leucovorin, Oxaliplatin, and Docetaxel and was administered in 2, four week cycles. Chemotherapy consisted on day one and day fifteen; Oxaliplatin, Docetaxel, FUDR, and Leucovorin. The latter two drugs were given concurrently over twenty four hours. On day eight, chemotherapy consisted of Docetaxel, FUDR, and Leucovorin. Following therapy, patients underwent surgical resection. Those patients having residual disease were offered adjuvant chemotherapy. Patients having a complete pathological response were not offered any further therapy. Results: Twenty-four out of twenty-nine patients completed neoadjuvant therapy and underwent esophagectomy. Two were declared inoperable after treatment. Three patients died prior to surgery. The median follow-up of all patients is now sixty months. The median overall survival has not been reached at sixty months. Five yr actual OS is 51%. Clinical response to neoadjuvant therapy was seen in (72.4%) patients. Complete pathological response to neoadjuvant therapy was seen in (16.7%) who are disease free at sixty month follow-ups. Seven out of twenty-four patients achieved partial pathological response (29.1%) and received adjuvant chemotherapy. They are all alive (100%). Eight patients achieved less than partial pathological response and received adjuvant chemotherapy, four out of eight are alive at sixty months (50%). Grade three and four toxicities were seen in sixteen out of twenty nine patients during neoadjuvant therapy. Grade three and four toxicities were seen in six out of fourteen patients during adjuvant therapy. Conclusions: Our chemotherapy regimen of Floxuridine, Leucovorin, Oxaliplatin and Docetaxel (FLOD) has resulted in long term survival in patients with adenocarcinoma of the esophagus. Clinical trial information: NCT00448760.
Patterns of radiotherapy and its impact on survival in patients with locally advanced gastric and gastroesophageal junction adenocarcinoma: Before and after the publication of the MAGIC trial.
Authors: Lin Chi , Bhirud Abhijeet , Bennion Nathan Ronald 
Published: February 2017

125 Background: The intergroup 0116 trial for locally advanced gastric (GA) and gastroesophageal junction adenocarcinoma (GEJA) established postoperative chemoradiation therapy as the standard of care. However, since the publication of the MAGIC trial in 2006, some physicians prefer perioperative chemotherapy rather than postoperative chemoradiation. The goal of this study is to examine the use of radiotherapy (RT) and its impact on survival in patients diagnosed 3 years prior to and after the publication of the MAGIC trial. Methods: Patients with stage T2-4 or N+ and M0 GA (3339) or GEJA (1868) diagnosed between 2004 and 2009 who have had a primary tumor resection with at least 3 years of follow up were identified from the SEER database. Regression models were used to analyze factors influencing the use of RT and its effect on survival. Kaplan Meier plots and log-rank tests were used for survival comparisons. Results: From 2004 to 2009, there was no change in the ratio of RT/no RT. About 33% of patients with GA and 53% with GEJA received RT. Multivariate regression analysis showed that patients with T2-3 disease, N+ disease, and younger patients were more likely to receive RT in both GA and GEJA. The median follow-up for GA and GEJA, was 73 and 68 months and median survivals of 27 and 26 months respectively. RT improved median survivals from 20 to 46 months for GA and from 20 to 31 months for GEJA (p < 0.0001). After adjusting for stage and age, patients who received RT had higher odds of surviving 3 years or longer for both GA (OR 2.20, 95% CI 1.86-2.60) and GEJA (OR 1.46, 95% CI 1.19-1.80). Further analysis revealed that RT improved survivals in patients diagnosed either before or after 2006 for both GA and GEJA. Conclusions: The publication of MAGIC trial in 2006 has not affected the patterns of using RT on locally advanced GA or GEJA. Patients who did not receive RT after 2006 continue to have worse survival rates compared to those who have had RT. Further studies are warranted to evaluate the effect of combining the MAGIC chemotherapy regimen and RT on survival and quality of life of these patients.
A phase II trial of trastuzumab combined with irinotecan in patients with advanced HER2-positive chemo-refractory gastric cancer: OGSG1203 (HERBIS-5).
Authors: Nishikawa Kazuhiro , Sakai Daisuke , Kawada Junji , Kawabata Ryohei , Kawase Tomono , Oka Yoshio , Sugimoto Naotoshi , Shimizu Takeshi , Nishijima Junichi , Hasegawa Hiroko , Endo Shunji , Isozaki Yutaka , Kimura Yutaka , Matsuyama Jin , Kurokawa Yukinori , Shimokawa Toshio , Fujitani Kazumasa , Satoh Taroh 
Published: February 2017

128 Background: Irinotecan is a key drug in second- or further-line chemotherapy for patients with advanced gastric cancer. Continuous administration of trastuzumab beyond first progression is expected to contribute to the benefit of chemotherapy for HER2-positive gastric cancer. We assessed the efficacy and safety of combination chemotherapy with trastuzumab and irinotecan in Japanese patients with advanced HER2-positive chemo-refractory gastric cancer. Methods: Intravenous infusion of irinotecan every 2 weeks at a dose of 150 mg/m2; intravenous infusion of trastuzumab at a dose of 8 mg/kg on day 1 of the first cycle, followed by 6 mg/kg every 3 weeks. Administration of irinotecan and trastuzumab were repeated in independent schedules. The primary endpoint was disease control rate. The secondary endpoints were adverse events, response rate, time-to-treatment failure, progression-free survival, overall survival, and response rate stratified by prior trastuzumab use. This study was conducted by the Osaka Gastrointestinal Cancer Chemotherapy Study Group (OGSG). Results: From October 2012 to Augst 2014, 30 patients were enrolled and one patient withdrew before study treatment. Accordingly, 29 patients were assessable for efficacy and safety. The disease control rate was 65.5% [95% C.I. 45.7 - 82.1%], and the response rate was 20.7% [95% C.I. 8.0 - 39.7%]. The median progression free survival and the median overall survival were 3.7 and 7.5 months, respectively. The major grade 3/4 toxic effects were neutropenia (24%); anemia (24%); leucopenia (21%); anorexia (11%); fatigue (14%); hypoalbuminemia (24%); and hypokalemia (14%). One death (NOS) was considered to be related to the study. Conclusions: The results of combination Trastuzumab with irinotecan showed feasible and promising efficacy against advanced HER2-positive chemo-refractory gastric cancer. These findings indicated that trastuzumab continuation use might be beneficial. Clinical trial information: 000008626.
Clinical impact of preoperative albumin to globulin ratio in gastric cancer patients with curative intent.
Authors: Toiyama Yuji , Okigami Masato , Yasuda Hiromi , Ohi Masaki , Tanaka Koji , Inoue Yasuhiro , Mohri Yasuhiko , Kusunoki Masato 
Published: February 2017

13 Background: Albumin to globulin ratio (AGR) has mainly been used as a clinical indicator for multiple myeloma or other immunoproliferative diseases. Recently, AGR has been reported to predict long term mortality in patients with nasopharyngeal carcinoma, colorectal cancer, lung cancer and breast cancer. However, clinical impact of preoperative AGR in gastric cancer (GC) has not yet been addressed. Therefore, we, for the first time, investigated the association between AGR and clinico-pathological findings including overall survival (OS) and disease free survival (DFS) in GC patients with curative intent. Methods: Clinicopathological findings including preoperative laboratory data (carcinoembryonic antigen [CEA], carbohydrate antigen [CA] 19-9 and AGR) from 384 curative GC patients were assessed as indicators of early recurrence and poor prognosis in this retrospective study. AGR was calculated as [AGR = albumin/ (total protein - albumin)]. The cut-off value of AGR was 1.4 in current study. Results: Several pathological categories related with tumor progression such as lymph node metastasis, tumor serosal invasion, large tumor size, venous invasion were significantly associated with lower AGR levels. In addition, significant negative correlation between AGR and age was found. Among preoperative serum markers, AGR was an independent predictor of early recurrence in curative GC patients after adjusted by age and sex. On the other hand, 2 pathological factors such as lymph node metastasis and serosal invasion were independent factors to identify early recurrence in curative GC patients among postoperative categories. Furthermore, sub analysis revealed that GC patients with AGR < 1.4 showed significant poorer DFS in both lymph node metastasis and serosal invasion group, respectively. Conclusions: Preoperative AGR may represent a simple, potentially useful predictive biomarker for selecting GC patients who might need neoadjuvant chemotherapy. Furthermore, AGR may select candidates who are better to introduce more intensive adjuvant chemotherapy after curative operation in stage II-III GC.
Preoperative prediction of peritoneal metastasis in gastric cancer as an indicator for neoadjuvant treatment.
Authors: Mori Koichiro , Toiyama Yuji , Ohi Masaki , Nagano Yuka , Uratani Ryo , Oki Satoshi , Okigami Masato , Yasuda Hiromi , Saigusa Susumu , Tanaka Koji , Inoue Yasuhiro , Mohri Yasuhiko , Kusunoki Masato 
Published: February 2017

14 Background: Although Gastric cancer (GC) mortality has been reduced by advances in new treatments and in chemotherapy, it still has a poor prognosis and high mortality. One of the reasons for poor prognosis is that at the time of diagnosis advanced GC with metastatic disease is often detected and it is frequently accompanied by peritoneal metastasis. Imaging studies are frequently used to predict peritoneal metastasis, however, these modalities did not obtain consistently high sensitivity and specificity in assessing peritoneal metastasis. Therefore, we investigated whether the combination of several serum markers and clinical factors could be used for preoperative prediction of peritoneal metastasis in GC as an indicator for neoadjuvant treatment. Methods: A total of 493 patients with GC were enrolled in our Hospital. Preoperative serum tumor markers [carcinoembryonic antigen (CEA) and carbohydrate antigen (CA)19-9], systemic inflammatory marker C-reactive protein (CRP), host immune markers [neutrophil and lymphocyte counts and their ratio (NLR)], albumin as a nutritional marker, and objective preoperative clinical factors were available as indicators of postoperative peritoneal metastasis. Results: This study included a total of 344 men and 149 women who were classified according to UICC TNM Classification: 264 patients had stage I disease, 79 stage II, 78 stage III and 72 stage IV. Specific clinical factors, including tumor size, histopathology of biopsy sample, and tumor morphology, were significantly correlated with peritoneal metastasis. CA19-9, lymphocyte count and NLR were also predictive factors for peritoneal metastasis. Multivariate analysis identified the clinical factors tumor morphology and histopathology, and laboratory markers CA19-9 and lymphocyte count as independent factors predictive for peritoneal metastasis. Next, a combination of independent predictive factors achieved high predictive accuracy (0.882) for peritoneal metastasis preoperatively. Conclusions: A combination of preoperative tumor features and serum parameters is an alternative method to preoperatively discriminate patients with GC with peritoneal metastasis from those without.
Trastuzumab induced cardiotoxicity in HER2-positive metastatic esogastric cancers.
Authors: Martin-Babau Jerome , Eusen Yves , Verveur Cedric , Trouboul Fanny , Cheneau Caroline , Jestin Le Tallec Veronique , Simon Helene , Metges Jean-Philippe 
Published: February 2017

152 Background: Trastuzumab is widely used in Her2 positive metastatic esophageal and gastric cancers along with chemotherapy. Cardiotoxicity of trastuzumab has been described precisely in Her2 positive breast cancers and occurs with asymptomatic lowering of LVEF (Left Ventricular Ejection Fraction) in up to 10% of cases. Esogastric cancer patients are usually older and have more comorbidities than patients followed for breast cancer. Methods: This monocentric retrospective study measured the incidence of symptomatic and asymptomatic cardiotoxicity in patients treated for metastatic esogastric cancers and its potential impact regarding overall survival from October 2009 to September 2015. Patients should receive trastuzumab with chemotherapy during the period of study for treatment of Her2 positive metastatic esogastric cancer as first-line chemotherapy. Results: 27 patients received trastuzumab along with chemotherapy during the period of study. Median age was 62.3 years, sex ratio 21 M/6 W. The median number of cycles of trastuzumab was 5 cycles. The asymptomatic cardiotoxicity rate, defined by a drop of more than 10% of LVEF between the enrollment echocardiogram and the third month treatment echocardiogram, was of 22%. Symptomatic cardiotoxicity was observed in two patients (7.4%), with one cardiac failure and one myocardial infarction, with no associated death. Cardiovascular comorbidities and cardiac irradiation which is recurrent in this indication did not appear as a predictive factor of cardiotoxicity (p = 1). Overall survival of patients was not statistically modified by the occurring of cardiotoxicity even if we noted a trend to better outcome of the patients presenting an asymptomatic LVEF lowering. Conclusions: This study is to our knowledge the first to focus specifically on the cardiotoxicity of trastuzumab in esogastric metastatic Her2 positive cancer in the real world. These patients seem to be at a higher asymptomatic cardiac risk than breast cancer patients. However cardiovascular comorbidities didn’t appear as predictive factors of trastuzumab induced cardiotoxicity and should not prevent patient from benefiting of this treatment.
Pathologic and clinical outcomes in cT2N0 esophageal cancer: A cohort study.
Authors: Bhuchar Gauri , Altujjar Mohammad , Raja Siva , Murthy Sudish C. , Raymond Daniel , Videtic Gregory M.M. , McNamara Michael J. , Khorana Alok A. , Adelstein David J. , Sohal Davendra 
Published: February 2017

157 Background: The management of clinically staged T2N0 (cT2N0) esophageal cancer remains controversial and clinical staging can be inaccurate. We evaluated concordance between clinical and pathologic staging as well as outcomes in a cohort study of patients initially staged as cT2N0. Methods: We conducted a cohort study of consecutive patients with esophageal cancer staged as cT2N0 after imaging (CT, PET scans) and endoscopic ultrasound, who underwent surgical resection and were followed at the Cleveland Clinic from Jan 2000 to Jun 2014. Clinical, chemotherapy (CT), radiation (RT), pathologic, and survival details were evaluated. For statistically significant associations, adjusted hazard ratios (HR) with 95% confidence intervals (CI) and 2-sided p-values are presented. Results: The study population comprised 66 consecutive patients with cT2N0 esophageal cancer. Median age was 60 years; 76% were male; 97% were Caucasian. Gastroesophageal junction was the primary site in 56%; distal esophagus in 29%; middle esophagus in 14%; histology was adenocarcinoma in 62 (94%) cases. 20 patients received preop treatment (Rx): CT+RT (15), CT (5). In patients without preoperative Rx (n = 46, 70%), pathologic staging was > T2N0 in 54% (n = 25; T3 = 17, T4 = 1, N+ = 20), < T2N0 in 37% (n = 17), and T2N0 in 9% (n = 4). No < T2N0 or T2N0 patient received postop Rx. Of 25 > T2N0, 15 received postop Rx: CT+RT (14), CT (1). 5-fluourouracil-cisplatin was the most common CT regimen. Median overall survival (mOS) after 7 years of median follow-up was: overall, 48 mths (34 deaths, 52%); < T2N0/T2N0, 93 mths; > T2N0 with postop Rx, 69 mths; > T2N0 without postop Rx, 15 mths (p > 0.05 for comparison). Only node-positive disease on pathology was associated with mortality (mOS for N+ vs. N- was 28 vs. 118 mths, HR for mortality = 2.74, 95% CI = 1.30-5.76, p = 0.008); T-stage, surgical margins, timing or type of therapy were not. Conclusions: Clinical staging of cT2N0 esophageal cancer is concordant with pathologic staging in less than 10% of patients; a majority are under-staged. Strong consideration should be given to pre- or post-operative treatment in this population. Improvements in clinical staging approaches are urgently needed to avoid over- and under-treatment in this setting.
Correlation of locoregional treatment failures with radiotherapy target volumes after radiochemotherapy for esophageal cancer.
Authors: Gani Cihan , Fischer Stefan Georg , Zips Daniel 
Published: February 2017

166 Background: Radiotherapy is a mainstay in curative treatment concepts of esophageal cancer. Despite extensive treatment fields locoregional recurrences are frequent. We therefore aimed to evaluate the exact patterns of locoregional recurrence and correlate these recurrences with radiotherapy target volumes. Methods: Diagnostic PET-CT or CT imaging studies showing locoregional recurrences after preoperative or definitive radiochemotherapy for squamous or adenocarcinoma of the esophagus were matched with CT scans used for treatment planning. Distance of the recurrence from the Clinical Target Volume (CTV), Planning Target Volume (PTV) and the dose at the failure site were the determined. Target volume definition was in line with international standards. Results: We identified 104 patients treated with either definitive (n = 81) or preoperative radiochemotherapy (n = 23). After exclusion of patients with a history of second malignancies we found 25 locoregional recurrences in 20 patients. Median time to locoregional failure was 8 months (range 2-26 months). Six of 25 recurrences (24%) were located intraluminal in the initial Gross Tumor Volume (GTV), three of 25 (12%) were in-field nodal failures and five (20%) more than 1 cm distant from the PTV. Nine (36%) locoregional recurrences occurred within 1 cm of the cranial or distal end of the CTV, between the CTV and PTV or out-of-field adjacent to the PTV. Two patients developed anastomotic recurrence after surgery. Conclusions: Matching of diagnostic CTs showing local recurrences with radiotherapy planning CT data set allows the correlations of local recurrences with target volumes. Despite extensive safety margins, field margin recurrences remain a considerable problem in the treatment of esophageal cancer. The use of advanced radiotherapy techniques might facilitate larger treatment volumes without increasing toxicity.
Factors predictive of tumor recurrence and overall survival in patients with esophageal cancer who have pathologic complete response after neo-adjuvant therapy.
Authors: Gangi Alexandra , Hoffe Sarah E. , Frakes Jessica M. , Almhanna Khaldoun , Pena Luis , Fontaine Jacques , Blackham Aaron Udell , Pimiento Jose Mario 
Published: February 2017

170 Background: Pathologic complete response (pCR) to neoadjuvant therapy is presumably associated with favorable outcomes in patients (pts) with esophageal cancer, but reported survival rates vary. This study evaluates patterns of recurrence after curative esophagectomy and identifies factors predictive of recurrent disease and overall survival (OS) in patients with pCR. Methods: An IRB-approved, retrospective review of a prospective esophageal cancer database was conducted. Patient demographics, perioperative data, and outcomes were examined. Recurrences were classified as locoregional (LR) or systemic. Cox regression model and Kaplan–Meier (KM) plots were used for survival analysis. Results: 837 pts with invasive esophageal cancer treated at a single institution from 1994 to 2013 were identified. 176 pts underwent neoadjuvant therapy followed by surgery and had pCR. Of these, 93.7% had adenocarcinoma and 6.3% had squamous cell cancer. Mean age was 56.6 and most pts were white (96.6%) males (79.5%). Median follow up was 42.6 months. 95 pts were treated before 2007 and 81 after. Most pts (85%) underwent transthoracic esophagectomy. All 176 pts received chemotherapy and radiation; dose-specific information was available on 144 pts, of whom most received 50.4 Gy (45%). 170 pts had recurrence data available: 39 (22.9%) had recurrent disease at a mean of 18.3 months; 5 (2.9%) with LR and 34 (20%) with systemic disease. On multivariate analysis, when evaluating patient demographics, pretreatment stage, type of surgery, type of chemotherapy, and number of lymph nodes resected, only pretreatment stage was associated with recurrence (p = 0.04). Median time to recurrence was 26.3 months for LR disease and 10.9 months for systemic disease (p = 0.3). KM estimates determined that pre-treatment stage and time of treatment ( < 2007 or ≥ 2007) were predictive of improved OS (p < 0.01, = 0.03). Conclusions: The incidence of disease recurrence in pts who experience pCR is low. The pretreatment stage and time of treatment were independent predictors of improved OS. Enhancing treatment strategies to maximize pCR would improve outcomes in pts with esophageal cancer.