bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety profile of thoracoscopic esophagectomy for esophageal cancer compared with traditional thoracotomy from the results of JCOG0502: A randomized trial of esophagectomy versus chemoradiotherapy.
Authors: Nozaki Isao , Kato Ken , Igaki Hiroyasu , Ito Yoshinori , Daiko Hiroyuki , Yano Masahiko , Udagawa Harushi , Nakagawa Satoru , Takagi Masakazu , Okabe Hiroshi , Abe Tetsuya , Nakamura Tetsu , Hihara Jun , Toh Yasushi , Akutsu Yasunori , Shibuya Yuichi , Mizusawa Junki , Nakamura Kenichi , Fukuda Haruhiko , Kitagawa Yuko 
Published: February 2017

82 Background: Esophagectomy for esophageal cancer via the thoracoscopic approach (TA) is expected to reduce the extent of trauma compared with traditional thoracotomy (TT). However, there have been few prospective studies comparing perioperative complications between TA and TT after esophagectomy. Therefore, this study aimed to clarify whether TA is a safe procedure with regard to morbidity and mortality using the data of patients (pts) who underwent esophagectomy in the JCOG0502 trial. Methods: The JCOG0502 trial is a currently on-going randomized trial including a patient preference arm of esophagectomy versus chemoradiotherapy for treatment of clinical stage I esophageal cancer. The primary analysis of overall survival is planned in 2018. In this trial, thoracic squamous cell carcinoma, adenosquamous carcinoma, and basaloid carcinoma of stage T1b/N0/M0 were eligible. When pts were randomized to surgery or selected surgery, esophagectomy with D2–3 lymphadenectomy was performed. TA or TT was selected at the surgeon’s discretion. Perioperative complications were defined as adverse events of grade 2 or greater as per CTCAE v3.0. Results: A total of 379 pts (11 randomized and 368 in the patient preference arm) were enrolled between December 2006 and February 2013 from 37 institutions, and 211 pts underwent surgery. Of these 211 pts, TA was performed in 101 pts while TT was performed in 110 pts. Blood loss was less in the TA group than in the TT group (median, 293 vs. 410 mL, respectively), and the surgical duration was longer in the TA group than in the TT group (median, 510 vs. 398 min). The proportion of intraoperative complications was similarly low in both groups. However, postoperative anastomotic leakage, pneumonia, and atelectasis were less common in the TA group than in the TT group (7%, 8%, and 11% vs. 14%, 17%, and 22%). Moreover, the proportion of recurrent nerve palsy was similar among both groups (15% vs. 16%). Each group had one in-hospital death. Conclusions: This study indicated that TA did not increase morbidity or mortality after esophagectomy and can be safely performed with risks comparable to those with TT. Clinical trial information: UMIN000000551.
Phase II study of trastuzumab in combination with capecitabine and oxaliplatin in patients with advanced gastric cancer.
Authors: Ryu Min-Hee , Ryoo Baek-Yeol , Park Young Soo , Park Sook Ryun , Kim Jong Gwang , Han Hye-Suk , Chung Ik-Joo , Song Eun-Kee , Lee Kyung Hee , Kang Seok Yun , Kang Yoon-Koo 
Published: February 2017

83 Background: Trastuzumab (Herceptin) in combination with capecitabine and cisplatin has been the standard first-line chemotherapy in patients with HER2-positive advanced gastric cancer (AGC). Oxaliplatin is generally less toxic and more convenient than cisplatin, and currently replacing cisplatin for the treatment of AGC. This study aims to investigate the efficacy and safety of trastuzumab in combination with capecitabine and oxaliplatin (HER-XELOX) in HER2-positive AGC. Methods: With Simon’s minimax two stage design (P0[response rate of historic control]=0.4, P1=0.55, two-sided alpha=0.1, beta=0.2, and 10% drop-out rate), a total of 55 patients with AGC positive for HER2 defined as either HER2 immunohistochemistry (IHC) 3+ or IHC 2+and FISH+ were enrolled from Aug 2011 to Feb 2013. HER-XELOX regimen consisted of trastuzumab 8 mg/kg i.v. on day 1 in cycle 1 and then 6 mg/kg in subsequent cycles, capectabine 2000 mg/m2/day p.o. on days 1-14, and oxaliplatin 130 mg/m2i.v. on day 1, every 3 weeks. HER-XELOX was administered as a first-line chemotherapy until disease progression, unacceptable toxicity, or consent withdrawal. Results: Among the 55 patients, 37 (66%) patients were male. Median age was 57 years (range, 29-74). ECOG performance status was 0-1 in 51 (93%) patients. Fifty three (96.4%) patients had metastatic disease, and 2 (3.6%) had locally advanced unresectable disease. With complete response in 2 patients and partial response in 35 patients, confirmed overall response rate was 67.3% (95% CI, 54-80%). With a median follow-up of 13.8 months (range, 6.1-23.9) in surviving patients, median progression-free survival was 9.8 months (95% CI, 7.0-12.6). Median overall survival was 21.0 months (95% CI, 6.4-35.7). Common grade 3 or 4 toxicities with frequency > 10% included neutropenia (18.2%), anemia (10.9%), and neuropathy (10.9%). There was no febrile neutropenia. One patient died of treatment-related diarrhea and sepsis. Conclusions: HER-XELOX regimen is well tolerated and highly effective in patients with HER2-positive AGC. Clinical trial information: NCT01396707.
Utilization of laparoscopy for resections of stomach and esophagus cancers: Is hospital the deciding factor?
Authors: Bliss Lindsay A. , Chau Zeling , Yang Catherine J. , Smith Jillian K. , Witkowski Elan R. , Ragulin-Coyne Elizaveta , Ng Sing Chau , Critchlow Jonathan F. , Moser Arthur J. , Tseng Jennifer F. 
Published: February 2017

86 Background: Foregut surgery is technically complex. Outcomes for such high-stakes operations receive increasing scrutiny and the use of minimally invasive approaches has been further adopted. This study aims to determine national trends in laparoscopy utilization and patient outcomes for potentially curative cancer resections of the esophagus and stomach. Methods: Retrospective review of all esophageal and gastric cancer resections in the Nationwide Inpatient Sample during 1998 to 2011. Univariate analyses of sex, race, admission status, Elixhauser comorbidity score, year, insurance, hospital characteristics, procedure, and center volume were performed by chi-square. Cochran-Armitage test was used for trends. Logistic regressions were used to model inpatient mortality, complications and laparoscopy. Results: From 1998 to 2011, 120,527 and 25,540 patients (nationally-weighted records) underwent gastrectomies and esophagectomies for cancer. From early (1998-2002) to late (2008-2011) study years, inpatient mortality decreased from 6.69% to 3.88% (<0.0001) and complications increased from 27.41% to 31.63% (<0.0001) for gastrectomy. Similarly, inpatient mortality decreased from 9.75% to 5.53% (<0.0001) and complications increased from 37.69% to 43.07% (<0.0001) for esophagectomy. Use of laparoscopy in gastrectomy increased from 1.64% to 5.89% (p <0.0001) and in esophagectomy from 0.80% to 5.74% (<0.0001). Patients undergoing laparoscopy had lower inpatient mortality (3.13% vs. 5.96%, p=0.0010) and were less likely to experience complications (26.20% vs. 31.47%, p=0.0121). After adjustment, independent predictors of the use of laparoscopy included elective admission, female sex, resection after 2003 and resection at a large (vs. medium), urban, teaching high volume center (vs. low volume center) in the Northeast (vs. Midwest and South). Conclusions: Inpatient mortality and complications for gastrectomy and esophagectomy have improved over the past decade. Use of minimally invasive techniques is expanding with associated superior patient outcomes. Resection hospital characteristics drive which patients undergo laparoscopy for esophagus and stomach cancers.
A randomized phase III trial of second-line chemotherapy comparing CPT-11 alone versus S-1 plus CPT-11 combination therapy in advanced gastric cancer refractory to first-line therapy with S-1 (JACCRO GC-05).
Authors: Nishikawa Kazuhiro , Tanabe Kazuaki , Fujii Masashi , Kunisaki Chikara , Tsuji Akihito , Matsuhashi Nobuhisa , Takagane Akinori , Ohno Tetsuro , Kawase Tomono , Kochi Mitsugu , Yoshida Kazuhiro , Kakeji Yoshihiro , Ichikawa Wataru , Chin Keisho , Terashima Masanori , Takeuchi Masahiro , Nakajima Toshifusa 
Published: February 2017

87 Background: In East Asia, S-1 + CDDP (SP) has been employed as first-line therapy for advanced gastric cancer (AGC) from the results of SPIRITS trial. Patients who were resistant to chemotherapy with S-1 in the first-line treatment were widely treated with taxane alone or CPT-11 alone as the second-line treatment. On the other hand, the response rate of combination therapy with S-1 is higher than that of CPT-11 alone. Then, we hypothesized that S-1 + CPT-11 prolongs survival in the second-line treatment comparing with CPT-11 alone after failure in the first-line treatment with S-1. (NCT00639327). Methods: Patients with AGC who confirmed disease progression by imaging after the first-line therapy with SP, S-1 + cocetaxel or S-1 alone except S-1 + CPT-11 were allocated into S-1 plus CPT-11 group (Group A) or CPT-11 alone group (Group B) as second-line chemotherapy. Patients who were relapsed to adjuvant chemotherapy with S-1 were not enrolled. Primary endpoint was overall survival, and secondary endpoints were progression free survival, response rate and adverse events. Results: From March 2008 to June 2011, 304 patients were enrolled, and 294 were eligible for analysis. The overall survival was 8.8 months (M) in the Group A and 9.4M in the Group B. There is no statistically significant difference in both groups (P=0.9156). The progression free survival was 4.8M in the Group A and 4.9M in the Group B (P=0.1568). The response rate was 7.6% in the Group A and 7.4% in the Group B. Grade 3 or higher leukopenia, neutropenia and febrile neutropenia were observed more frequently in the Group A than in the Group B. Conclusions: From our results, we do not recommend consecutive use of S-1 as second-line treatment in patients who are refractory to S-1 in first-line chemotherapy. Clinical trial information: 00639327.
ICORG 06-41: A phase II trial of single-agent sorafenib in the treatment of platinum-pretreated relapsed gastroesophageal adenocarcinoma (GECa).
Authors: Connell Louise Catherine , O'Reilly Seamus , Webb Glenn , Moulton Brian , Parker Imelda , McDermott Raymond , McCaffrey John , Grogan William , Leonard Gregory , Power Derek Gerard , Horgan Anne M. , Bird Brian , O'Byrne Kenneth John 
Published: February 2017

88 Background: Over 1 million individuals worldwide annually are diagnosed with GECa. The majority of patients(pts) present with inoperable locally advanced or metastatic disease(dx). Even with resectable dx 5 year survival is low at ~40% with current best treatment (tx). Following initial platinum based therapy there is no established standard 2nd line tx. Besides HER2-directed therapy there has been little progress with targeted biologic agents. ICORG, the all-Ireland Cooperative Oncology Research Group investigated the utility of the tyrosine kinase inhibitor sorafenib in a multicentre trial. Methods: A prospective Phase II, nonrandomised, open label, one arm study of single agent sorafenib in the tx of platinum pre-treated relapsed GECa was conducted. Primary objective was dx control rate (DCR) post 4 months of tx. Secondary endpoints were OS, PFS, TTP, ORR, tolerability/toxicity and biomarkers of tx response/resistance. The protocol allowed for an interim analysis to be performed if clinically indicated. A sample size of 54 pts was identified using the single stage Fleming design approach to test whether the proportion responding, P, is ≤ 0.35 or ≥ 0.50. Pts received Sorafenib 400mg bid p.o. continuously q28days until dx progression or intolerable toxicity. Response by RECIST was evaluated by CT q8weeks. For pts with sufficient tumour samples translational studies were done. Results: An interim review performed in Nov 2012 (35 months post study opening) indicated that 33/41 evaluable pts recruited to date had progressed before completing 4 months of tx. Therefore, the number of evaluable pts with dx control could not reach the pre-specified figure of 22, & the hypothesis P >= 0.50 was rejected. Fifteen pts had just 1 cycle of tx, 5 of whom completed ≤ 2 weeks. A further 14 pts had 2 cycles. Median survival time to progression was 56 days (95% CI 53 – 59 days).Median OS was 120 days (95% CI 91 – 149 days). Safety data analyses and translational studies are ongoing and will be available for presentation at the meeting. Conclusions: Sorafenib as monotherapy is inactive in platinum pretreated pts with relapsed GECa. A significant unmet clinical need for novel effective therapies remains. Clinical trial information: 2008-005062-31.
Serum angiopoietin-like protein 2 as a novel biomarker of diagnosis and prognosis in gastric cancer.
Authors: Toiyama Yuji , Inoue Yasuhiro , Kitajima Takahito , Shimura Tadanobu , Imaoka Hiroki , Kondo Satoru , Ide Shozo , Okigami Masato , Yasuda Hiromi , Saigusa Susumu , Ohi Masaki , Tanaka Koji , Mohri Yasuhiko , Kusunoki Masato 
Published: February 2017

9 Background: Angiopoietin-like protein 2 (ANGPTL2) is a secreted glycoprotein with homology to the angiopoietins and is known to act as a causative mediator of chronic inflammation and inflammatory carcinogenesis. Recently, we demonstrated that ANGPTL2 overexpresses in gastric cancer (GC) compared to normal gastric mucosa and high ANGPTL2 is associated with poor prognosis. Therefore, if tumor-derived ANGPTL2 over-secretes systemically, focusing ANGPTL2 in blood is logical to evaluate its ability as a biomarker. Accordingly, we quantified serum ANGPTL2 level and assessed its clinical significance in GC patients. Methods: We screened serum ANGPTL2 levels from 32 GC and 24 normal controls (NC) by ELISA (cohort 1). Next, we validated 194 serum samples from GC and 48 NC (cohort 2). Finally, we examined ANGPL2 expression in matched GC tissues of cohort 2 (n=194) by immunohistochemistry (IHC). The IHC score of ANGPTL2 was determined on the basis of both staining intensity and the percentage of positive cells. Results: In cohort 1,serum ANGPTL2 levels in GC were significantly higher than that in NC (p<0.05). Serum ANGPTL2 differentiated GC from NC with high accuracy (AUC=0.814). Analysis of cohort 2 also indicated that serum ANGPTL2 levels in GC were significantly higher compared to NC (p<0.0001), and increased according to UICC stage progression. In addition, serum ANGPTL2 had a promising AUC (0.831) with high sensitivity (73.0%) and specificity(82.2%) to distinguish GC from NC. High serum ANGPTL2 was significantly associated with lymphatic invasion (p=0.03), vessel invasion (p=0.02), distant metastases (p=0.0002), early recurrence (p=0.004) and poor survival (p=0.01), consequently emerged as an independent predicting recurrence marker (HR=5.06, p=0.0004) and prognostic marker (HR=3.6, p=0.01) in GC. Of interest, ANGPTL2 levels in serum from GC patients closely correlated with IHC scores of cytoplasmic ANGPTL2 at the invasive margin of matched GC tissues (r= 0.16, p=0.02). Conclusions: Serum ANGPTL2 levels, which might be secreted from primary or metastatic site into blood stream, have extremely strong potential as a novel biomarker for diagnosis, predicting recurrence and poor prognosis in GC patients.
FDG-PET scan after induction chemotherapy for esophageal squamous cell cancer (ESCC) to predict for outcomes after chemoradiation (chemoRT) and to guide salvage chemotherapy during RT.
Authors: Ku Geoffrey Yuyat , Janjigian Yelena Yuriy , Kriplani Anuja , Ong Leonard , Rusch Valerie W. , Bains Manjit S. , Rizk Nabil P. , Sarkaria Inderpal S. , Capanu Marinela , Goodman Karyn A. , Ilson David H. 
Published: February 2017

94 Background: Pre-operative or definitive chemoRT is accepted treatment for locally advanced (LA) ESCC. We have retrospectively shown that assessment by PET scan following induction chemo prior to chemoRT and surgery predicts outcomes in SCC Pts (Cancer 118:2820; 2012). Some Pts with progression on PET after induction chemo had long-term survival when changed to alternative chemo during RT. Methods: We retrospectively reviewed all Pts with LA ESCC who received induction chemo and chemoRT from 2002 to 2010; all Pts had PET scan before and after induction chemo. Results: 62 Pts were identified, median age 63, median Karnofsky performance status 80%, 75% with uN+ disease. 43 (69%) received induction chemo with platinum/irinotecan (CPT-11), 13 (21%) with platinum/paclitaxel and 6 (10%) with docetaxel/CPT-11 ± cisplatin. 38 Pts (61%) were PET responders (PETr; ≥35% decrease in mSUV of tumor) and 24 (39%) were PET non-responders (PETnr; <35% decrease). All PETr received same chemo during RT. Of PETnr, 9 continued with same chemo during RT and 15 were changed to a different chemo with RT. 33/38 PETr (87%) achieved a clinical complete response (cCR) vs. 4/9 (44%) of PETnr/no chemo change vs. 11/15 (73%) of PETnr/chemo change (p=0.01 for PETr vs. PETnr/no chemo change; p=0.25 for PETr vs. PETnr/chemo change). 17 Pts had resection, all R0; 5/12 PETr (42%) had pathologic CR (pCR) while 0/3 PETnr/no chemo change Pts had pCR. Median disease-specific survival (not reached vs. 19 mos, p=0.002) and overall survival (OS; 69.6 vs. 17.4 mos, p=0.0056) were significantly better for PETr vs. PETnr. Median OS for PETnr/chemo change was 19.6 mos vs. 13.3 mos for PETnr/no chemo change (p=0.50); 6/15 PET nr who had different chemo with RT have extended survival, including 4 who are without disease at 2.8 – 9+ years. Conclusions: PET scan after induction chemo appears to predict for outcomes in ESCC Pts who received chemoRT. Long-term survival is possible in PETnr who switch to different chemo during RT. Such a strategy should be prospectively evaluated in a clinical trial.
Predictors of disease control in patients treated with platinum-based chemotherapies for metastatic squamous-cell esophageal cancer: First results of the e-DIS trial.
Authors: Adenis Antoine , Bennouna Jaafar , Galais Marie-Pierre , Tresch Emmanuelle , Francois Eric , Etienne Pierre-Luc , Ben Abdelghani Meher , Michel Pierre , Seitz Jean-François , Conroy Thierry , Ghiringhelli Francois , Bedenne Laurent , Samalin Emmanuelle , Piessen Guillaume , Hiret Sandrine , Peugniez Charlotte , Herin Helene , Clisant Stephanie , Kramar Andrew , Mariette Christophe 
Published: February 2017

95 Background: There is little evidence that chemotherapy (CT) impacts on outcome of patients with MSEC. We designed an ongoing randomized phase 2 trial to detect a progression-free survival benefit of CT continuation over CT discontinuation in disease-controlled and ECOG≤2 patients at 6 weeks after an initial CT treatment. The aim of the present study was to identify predictors of disease control at 6 weeks (DC6wkx) in MSEC patients receiving platinum-based CTs as first-line treatment for metastatic disease. Methods: Among 68/70 evaluable patients included between 1/2011 and 7/2013 who received at least 1 CT cycle, 58 were evaluable for disease assessment at 6 weeks. Ten patients were not evaluable (early death: 4, patient’s decision: 2, concomitant disease 1, early progressive disease 1, other reasons: 2). Baseline demographic, clinical, biological, and tumor characteristics were tested for prediction of DC6wkx. Significant variables for DC6wkx were identified with the chi-squared test and logistic regression. Results: Baseline patients characteristics were as follows: median age: 61.5yo; male: 57/68; ECOG 0/1/2: 13/42/13; metachronous/synchronous MSEC: 38/30; number of metastatic sites 1/2/>2: 35/20/13; metastatic location: lung 36, liver 23, bone 11, nodes 37, other 11; prior exposure to CT: 37/68; time from previous CT exposure: ≤ 6m 6/37, 6-12m 14/37, > 12m 17/37; gr>2 dysphagia (Atkinson) 19/67; BMI<18.5kg/m²: 13/68. Current CTs were FU-CDDPq3w 2/68, LV5FU2-CDDPq2w 15/68, FOLFOX 51/68, and patients received the following number of cycles 1/2/>2: 5/7/54. DC6wkx rate was 65.7%, with 16/68 PR (23.5%) and 28/68 SD (42.2%). Albumin (p<0.01), BMI (p<0.02), bone metastases (p<0.005), gender (p<0.047) and ECOG status (p<0.05) were predictive of DC6wkx. Normal or overweight BMI, grade 0 albumin, and no bone metastases, were predictive of DC6wkx in multivariate analysis. Conclusions: DC at 6 wks was 65.7% in MSEC receiving platinum-based CTs as first line treatment for metastatic disease. Normal or overweight BMI, normal albumin, and the absence of bone metastasis were significant predictors of DC6wkx in this prospective phase 2 trial. Clinical trial information: NCT01248299.
Comparison of the long-term toxicities conferred by two different doses of definitive chemoradiotherapy for stage II/III esophageal squamous cell carcinoma.
Authors: Kubo Emi , Kato Ken , Okita Natsuko T. , Takashima Atsuo , Honma Yoshitaka , Iwasa Satoru , Hamaguchi Tetsuya , Yamada Yasuhide , Shimada Yasuhiro , Ito Yoshinori , Itami Jun 
Published: February 2017

96 Background: Deﬁnitive chemoradiotherapy is one of the options for stage II/III esophagealsquamous cell carcinoma (ESCC). RTOG9405 recently reported that a higher dose of radiation did not confer any additional survival benefit over the standard dose (50.4 Gy). We comparedthe long-term toxicities conferred by chemoradiation at a dose of 60 Gy and 50.4 Gy for stage II/III ESCC. Methods: Eligibility criteria included clinical stage II/III (non-T4) (UICC-TNM, 6th edition) ESCC, performance status 0-2, and age 20-75 years. The study group comprised 254 patients who received definitive chemoradiotherapy as first-line therapy between January 2000 and August 2010 in our hospital. Group J (n=207) received 2 cycles of cisplatin (40 mg/m2 on days 1 and 8) with fluorouracil infusion (400 mg/m2/day on days 1-5 and 8-12), or 2 cycles of cisplatin(70 mg/m2 on day 1) with fluorouracil infusion (700 mg/m2/day on days 1-4) and concurrent radiotherapy at 60 Gy. Group R (n = 47) received 2 cycles of cisplatin (75 mg/m2 on day 1) with fluorouracil infusion (1000 mg/m2/day on days 1–4) and concurrent radiotherapy at 50.4 Gy. Long-term toxicity was evaluated according to the Common Terminology Criteria for Adverse Event Ver. 3.0. Results: The characteristics of both groups are as follows (J:R group): median age, 64:63; male/female, 178/29:42/5; PS 0/1/2, 90/104/1:33/14/0; stage IIA/IIB/III: 48/58/101:6/20/21. The median follow-up period was more than 60 months for both groups, with 5-year survival rates of 43.6% and 58.6% for the J and R group, respectively. The proportion of patients with grade 3/4 long-term toxicity in each group was as follows (J/R group): pleural effusion, (8.7%/0%; p = 0.036); pericardial effusion, (6.7%/2.1%; p = 0.196); radiation pneumonitis, (2.4%/4.2%); esophagitis, (0.9%/0%); and pericarditis, (2.4%/0%). Grade 3/4 late toxicity was observed more frequently in the J group (15.0%) than in the R group (6.4%) (p = 0.087). Treatment-related death due to pneumonitis was observed in only 1 patient in group J. Conclusions: The RTOG regimen at a dose of 50.4 Gy showed promising results while inducing lower late toxicity rates than when administered at 60 Gy.