bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver transplantation (Ltx) in patients with nonresectable liver metastases from colorectal carcinoma.
Authors: Dueland Svein , Hagness Morten , Line Pal-Dag , Scholz Tim , Jorgensen P. , Fosby Bjarte , Mathisen Ostein , Gladhaug Ivar , Foss Aksel 
Published: February 2017

577 Background: Liver resection is considered the only curative treatment of liver metastases (mets) from colo-rectal (CRC) tumors. Ltx is standard of care in selected patients with hepatocellular carcinoma, cholangiocarcinoma and neuroendocrine tumors. Patients with non-resectable liver metastases (mets) from colo-rectal cancer (CRC) receiving palliative chemotherapy have a median survival of about 2 and 1 year from start of 1. and 2. line chemotherapy, respectively. Overall 5 years survival in CRC patients after start of palliative chemotherapy is about 5-10%. In this study we examined overall survival after Ltx in selected CRC patients. The primary endpoint of the study was overall survival at 2 years after Ltx Methods: Major inclusion criteria were: non-resectable liver mets, no extra hepatic disease or local relapse determined by PET/CT scan, CT- or MRI scan and colonoscopy. No mets. on frozen section biopsies at time of surgery, ECOG 0-1, at least one line of chemotherapy for metastatic disease. Postoperative immunosuppresion: mTOR inhibitor (Rapamune), mycofpenolmofetil and tapering doses of prednisolon. Quality of life questionnaire (EORTC-C30) pre Ltx, 3, 6 and 12 months post Ltx. Results: Thirteen men and 8 women with non-resectable liver only CRC liver mets received Ltx in the period of Nov 2006 to March 2011. Median age was 56 years (range 45-65 years). Thirteen patients had colon cancer and 8 patients had rectal cancer. The T-stage of the primary tumor was T2,T3 and T4 in 2, 16 and 3 patients, respectively. N status of the primary tumor was: pN0, pN1 and pN2 all 7 patients. Nine patients had received 1.line chemotherapy and 12 patients had received 2. or 3.line therapy. The median number of liver mets was 8 (range 2-40) and the median size of the largest lesion was 4.5cm (range 2.8-13cm). The patients had good, stabile or increased Global Health Score and Physical Function at all time points after Ltx. Fifteen patients with follow-up of 2 years or more or death within 2 years of Ltx had 2 years overall survival of 87%. Conclusions: Long term survival is obtained after Ltx in selected patients with non-resectable liver mets from CRC. The patients reported good quality of life and physical function after Ltx.
Does phase I radiotherapy dose of 30.6Gy in 17 fractions provide adequate microscopic nodal disease control in squamous cell carcinoma of the anus?
Authors: Augustin Yolanda Sydney , Tait Diana M. , Hawkins Maria 
Published: February 2017

588 Background: Definitive chemoradiation has been established as the standard of care for patients with squamous cell carcinoma of the anus. The ACT II study recommends 30.6Gy in 17 fractions for Phase I to the lower pelvis with a superior border 2 cm above the inferior aspect of the sacro-illiac joints, then a Phase II boost of 19.8Gy in 11 fractions to the tumor and involved nodes. Our goal was to retrospectively evaluate patterns of failure in the volumes that received microscopic dose 30.6Gy. Methods: Between January 2002 and December 2008, 106 patients with non-metastatic squamous cell carcinoma of the anus were treated with definitive chemoradiation. 81 (76.45%) of these patients received Phase I dose of 30.6Gy.The tumor stage was Tx or T1 in 18 % , T2 in 36% , T3 in 29%, and T4 in 12% of patients. The nodal stage was N0 in 57%, N1 in 13%, N2 in 14% and N3 in 11% of patients. The median radiotherapy dose was 50.4 Gy (range 50.4Gy -60 Gy). Concurrent chemotherapy was given with 5-fluorouracil (5-FU) and cisplatin in 12%, 5-FU and mitomycin C in 34%, capecitabine and mitomycin C in 38% and other regimens in 8% of patients. The median follow-up interval was 43 months (range 3.2 - 112.9 months). Results: A total of 21 patients (19.8%) experienced persistent or progressive disease during follow up. Out of this total, 16 patients received 30.6Gy in Phase I. Of these, 5 patients (4.7%) had persistent disease at the end of chemo-radiation, 4 patients (3.7%) relapsed in the anal region, 2 patients (2.4%) relapsed in the 30.6Gy area and 5 patients (6.2%) developed metastases. 8 patients with local recurrence/persistent disease underwent salvage surgery. Estimated 3 year rates for locoregional control and overall survival were 78% and 82% respectively. Conclusions: The majority of locoregional failures involve the anus and mesorectum, while nodal recurrence occurs rarely supporting the use of 30.6Gy for microscopic nodal disease control. This makes the case for dose escalation of primary tumours in Phase II. Placing the superior border of the radiotherapy field at 2 cm above inferior sacroiliac joints for phase I could potentially spare bone marrow and small bowel toxicity with minimal risk of nodal relapse.
Prognostic factors for long-term overall survival (OS) for patients (pts) undergoing first-line treatment for metastatic colorectal cancer (mCRC) with chemotherapy (CT) plus bevacizumab (bev): Findings from a large observational study.
Authors: Arnold Dirk , Grothe Wilfried , Tummes Dirk , Kindler Manfred , Petersen Volker , Boszeit-Luft Stefanie , Seraphin Joerg , Kutscheidt Andreas 
Published: February 2017

590 Background: Bev+CT has been shown to improve OS vs. CT alone in phase III and IV mCRC studies. However, as only a subset of pts experience OS >30 months (m), clinical factors may help to identify pt groups with the largest potential benefit. Methods: This large observational study included pts receiving bev with various first-line CT regimens in Germany from 2005–2009, with predefined assessment of OS, progression free survival (PFS), toxicity and 22 baseline variables, including pt characteristics, pre-treatment duration/procedures, blood parameters, tumour characteristics. Pts with long-term OS (defined as OS >30m) were compared to those with OS <30m. Surviving pts with observations <30m were defined as ‘censored’. Association between variables and OS was explored by univariate analyses and then multivariate analysis (logistic regression) to find independent variables for long-term OS. Results: 392 (22%) out of 1777 eligible pts had OS >30m (195 events, median OS 46.8m), 717 pts (40%) had OS <30m (median OS 14.3m), and 688 (38%) pts were censored. Median PFS was 17.7m (329 events) for pts with OS >30m, 7.7m for pts with OS <30m, and 11.8m (313 events) for censored pts. In the univariate analysis, nine variables were associated with OS >30m: age (continuous variable; p=0.0008), ECOG PS (0 vs. 1–4; p=0.0025), WBC <8.0/nL (p=0.013), CEA <20ng/mL(p<0.0001), single metastatic site (p<0.0001), initial pT4 vs. others (p<0.0001), pN0 vs. pN1/2 (p=0.0002), initial M0 vs. M1 (p=0.0021), grading G1/2 vs. G3/4 (p<0.0001). Independent variables for pts with OS <30m were found in the multivariate analysis. Conclusions: In general, the prognostic factors identifying long-term survivors in the CT only era are confirmed in this large cohort with bev treatment. However, the predominant role of grading and CEA level are remarkable. [Table: see text]
A phase II study of neoadjuvant chemotherapy with bevacizumab plus mFOLFOX6 for resectable synchronous liver metastasis (SLM) from colorectal cancer: The first report of the Miyagi Hepato-Biliary Pancreatic Clinical Oncology Group.
Authors: Katayose Yu , Yamauchi Junichiro , Oikawa Masaya , Sakurai Naoki , Musya Hiroaki , Shimamura Hiromune , Miura Koh , Nakagawa Kei , Egawa Shinichi , Unno Michiaki ,   Miyagi-HBPCOG
Published: February 2017

593 Background: The prognosis of synchronous liver metastases (SLM) from colorectal cancer is poor. Therefore, we conducted a phase II study of neoadjuvant chemotherapy for SLM to determine the appropriate initial treatment. Here, we assessed the effectiveness of bevacizumab combined with mFOLFOX6. Methods: Patients with SLM within 10 nodules were enrolled after R0-resection of the primary colorectal cancer, and received 8 courses of mFOLFOX6 with bevacizumab (the first and last courses were mFOLFOX6 only). The primary endpoint was response rate (RR). Results: Between June 2008, and November 2008, 47 patients (pts) were enrolled from 17 centers. The median age was 62 years (range 32-72 yrs). The median number of metastases was 2 nodules. Three pts were excluded from evaluation of RR because they did not receive any scheduled chemotherapy. The RR was 70.5% (2 complete responses and 29 partial responses). 11 pts (25%) showed stable disease and 2 pts (4.5%) had progressive disease. The liver resections rate was 90.9% (40 pts) and the R0-resection rate was 86.3%(38 pts). Adverse events in order of prevalence were sensory neuropathy, neutropenia, hypertension, leucopenia and so on. Grade 3 and 4 AEs occurred in 21 pts with the most common being Neutropenia. There were 3 Grade 4 AEs: renal failure and 2 pts of neutropenia. Grade 3 or 4 AEs are summarized below. There were no grade 5 AEs. Of note, liver resections were safely performed in the three pts with Grade 4 AEs. Conclusions: Neoadjuvant chemotherapy with bevacizumab plus mFOLFOX6 for liver metastases is effective and well tolerated. The benefit of this therapy as the initial treatment of SLMneeds to be evaluated further by comparison with adjuvant therapy. (This trial is on University hospital Medical Information Network-Clinical Trials Registry (UMIN-CTR). UMIN's unique trial number is UMIN000001568.) [Table: see text]
Phase II study of S-1 plus leucovorin (a new 1-week treatment regimen followed by a 1-week rest period) in patients with untreated metastatic colorectal cancer in Japan and China.
Authors: Denda Tadamichi , Li Jin , Xu Ruihua , Xu Jianming , Ikejiri Koji , Shen Lin , Toh Yasushi , Shimada Ken , Kato Takeshi , Baba Hideo 
Published: February 2017

598 Background: The previous phase II study of the oral S-1 plus oral Leucovorin (LV) (2 weeks’ treatment regimen followed by a 2 week rest period) for patients (pts) with untreated metastatic colorectal cancer (mCRC) have shown to be effective, but the grade 3 toxicities (diarrhea, stomatitis, and anorexia) were observed with relatively high frequency. In this phase II study, we tried to improve the administration schedule of S-1 plus LV regimens for well-tolerated toxicities and evaluated the efficacy. Methods: Pts were eligible as follows: histologically confirmed adenocarcinoma, age≥20, ECOG PS 0-1, no prior chemotherapy, at least one measurable lesion by RECIST ver1.0 criteria, adequate organ function, and written informed consent. S-1 (40-60 mg bid) and LV (25 mg bid) were orally administered for 1 week, followed by an 1 week rest period. Treatment was repeated until the onset of disease progression or unacceptable adverse events occurred. The primary endpoint was the response rate (RR), and the secondary endpoints were efficacy and safety. Results: From October 2008 to June 2009, 73 pts were enrolled in Japan and China. Of the eligible 71 pts, median age was 60 (range 27-84), Male/Female was 38/33, PS:0/1 was 39/32, and Japan/China was 32/39. RR as primary endpoint was 53.5% (95% CI, 41.3-65.5), and Disease Control Rate was 83.1%. With a median follow-up period of 26.4 months, the median Progression Free Survival was 6.5 months. Median Overall Survival was 24.3 months with the survival rate of 77.5 % at 1 year and 53.2 % at 2 years. The incidences of grade 3 adverse drug reactions were diarrhea 8.3 %, stomatitis 8.3%, anorexia 2.8%, neutropenia 9.7%, and there was no treatment-related death. Conclusions: The newly improved 1 week S-1 plus LV treatment regimen showed good efficacy and better tolerability than the 2 weeks’ treatment regimen. This therapy showed promising activity in pts with untreated mCRC without the concurrent use of irinotecan, oxaliplatin, or molecular-targeted drugs. This trial was supported by Taiho Pharmaceutical CO., LTD. ClinicalTrials.gov Identifier: NCT00891332 .
Phase II study alternating mFOLFOX 6 and FOLFIRI (FIREFOX) plus bevacizumab (bev) regimen in first-line treatment of advanced colorectal cancer in Japanese patients (KSCC 0801).
Authors: Ogata Yutaka , Akagi Yoshito , Kakeji Yoshihiro , Emi Yasunori , Oki Eiji , Saeki Hiroshi , Touyama Tetsuo , Samura Hironori , Baba Hideo , Natsugoe Shoji , Shirouzu Kazuo , Tokunaga Shoji , Maehara Yoshihiko ,   Kyushu Study Group of Clinical Cancer
Published: February 2017

602 Background: The Kyushu Study group of Clinical Cancer conducted a phase II study that evaluated the FIREFOX regimen. (KSCC0701, Akagi et al, J Clin Oncol 28:15s, 2010). This study demonstrated the efficacy and mild neurotoxicity of this regimen. The present study evaluated the efficacy and safety of the FIREFOX plus bevacizumab (bev). Methods: Eligibility criteria included histologically confirmed advanced colorectal cancer, ECOG PS 0-2 and adequate bone marrow, renal and hepatic function. Patients (pts) received an alternating regimen of 4 cycles of mFOLFOX-6 plus bev (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2, bev 5 mg/kg d1 followed by 400 mg/m2 bolus 5-FU and a 46-hr 2,400 mg/m2 5-FU infusion every 2 weeks) followed by 4 cycles of FOLFIRI plus bev (oxaliplatin replaced with irinotecan 150 mg/m2 d1). This schedule was repeated until unacceptable toxicity or disease progression occurred. The primary endpoint is progression-free survival. (UMIN000001312) Results: Of the 52 pts enrolled from May 2008 to July 2009. Two of the patients did not fulfill the eligibility criteria. M/F, 30/20; median age, 59.5 years (range 37 - 75); ECOG PS 0/1/2, 46/4/0. The median number of administration cycles was 14 (range, 2 - 44). Response rate (RECIST criteria) for CR, PR, SD, PD and NE were 2 (4%), 28 (56%), 14 (28%), 4 (8%) and 2 (4%), respectively. An overall response rate was 60% (95% CI: 45 - 74%). Median progression-free survival was14.2 M (95% CI: 10.6 M-16.3 M) and median overall survival was 27.5 M (95% CI; 22.4 M – not determined). The 2-year survival rate was 56.8%. Of the 52 pts evaluated for toxicity. The most common grade 3-4 adverse events were leukopenia (7.7%), neutropenia (32.7%), anemia (1.9%), fatigue (9.6%), anorexia (13.5%), stomatitis (3.8%), neurotoxicity (3.8%), hypertension (1.9%), diarrhea (7.7%), febrile neutropenia (3.8%), nausea (9.6%), vomiting (5.8%), hypersensitivity (3.8%), and thromboembolism (1.9%). Conclusions: The results of this phase II study show that the FIREFOX plus bev regimen is effective and well tolerated in the first-line treatment of advanced colorectal cancer. The low rate of neurotoxicity is also promising.
Cohort study evaluating the impact of a discharge letter (DL) compared with usual care on adherence to surveillance following treatment for stage II/III colorectal cancer (CRC).
Authors: Davies Janine Marie , Batuyong Eugene , Lupichuk Sasha M. , Hilsden Robert , Eliasziw Misha , Easaw Jacob C. 
Published: February 2017

620 Background: The 2005 ASCO guidelines recommend surveillance testing and frequencies following surgical +/− adjuvant therapy for stage II/III CRC. In Canada, many patients are discharged from their oncologist to their primary care physician (PCP) for ongoing surveillance. However, adherence to surveillance recommendations is low. This cohort study evaluated adherence to surveillance 1 year after treatment of stage II/III CRC prior to and following implementation of a DL. Methods: Cohort 1 (C1) patients were retrospectively identified from the Alberta Cancer Registry following adjuvant therapy (as applicable) at a tertiary cancer centre (07/2006 - 09/2007). Cohort 2 (C2) patients were prospectively identified from the Registry and clinic records following adjuvant therapy (as applicable), as those discharged from the centre (10/2007 - 4/2009); DL was sent to the patient and PCP recommending surveillance tests and dates. Clinical, laboratory, diagnostic imaging, and endoscopy data was collated. Adherence at 1 year follow-up was compared between cohorts using Kaplan-Meier time-to-event analyses. Results: C1 (n=218) was larger than C2 (n=114) despite the longer accrual time for C2. There were no differences between cohorts by age, sex, primary site of disease, stage, or adjuvant oxaliplatin use. During year 1 of follow-up, 11.8% and 11.4% recurred (local or metastatic) and 6.5% and 2.7% died (p=0.1) in C1 and C2 respectively. Comparing C1 with C2, 14.8% vs. 23.0% of patients had one CEA test within 3 months, 45.2% vs. 72.2% within 6 months, and 71.7% vs. 85.1% within 1 year (p<0.001). Only 44.0% (C1) and 68.6% (C2) had 2 CEA tests within 1 year. Only 3.9% (C1) vs. 6.6% (C2) of patients had 4 CEA tests within the year following treatment as recommended. The rate of CT imaging was 32.3% (C1) and 56.1% (C2); endoscopy was 36.7% (C1) and 42.1% (C2). Conclusions: Implementation of a DL improved compliance with surveillance at 1 year of follow-up following discharge from a tertiary cancer centre, although optimal adherence remains low. However, adherence to CT imaging nearly doubled. Evaluation of compliance at 3 years of follow-up is ongoing.
Phase I trial of yttrium 90 resin microspheres in the treatment of colon cancer liver metastases progressing despite hepatic arterial as well as systemic chemotherapy: Preliminary results.
Authors: Sofocleous Constantinos T , Kemeny Nancy E. , Pandit-Taskar Neeta , Do Kinh Gian , Brody Lynn A , Garcia Alessandra R , Capanu Marinela , Chou Joanne F. , Petre Elena N , Carrasquillo Jorge A. 
Published: February 2017

625 Background: Prospective evaluation of the safety of Selective Interval Radiation Therapy (SIRT) using yttrium 90 microspheres (Y90) in patients with colon cancer liver metastases (CLM) who failed hepatic arterial (pump) and systemic chemotherapy. Methods: This prospective single center study, assessed the safety, dose limiting toxicities (DLT) and the maximum tolerated dose (MTD) of Y90 in a selected, heavily pretreated population. Upon IRB and FDA approval individualized Y90 doses were calculated according to a volumetric method and the body surface area (BSA) method as instructed by the company. SIRT treatment was administered in three escalating dose levels (cohorts): the first cohort received 70%, the second 85%, and the third 100% of the calculated dose. All patients received chemotherapy as deemed by the patients' medical oncologist post SIRT treatment. DLT was defined as new, post treatment, grade 3 toxicities, and evaluated according to the NCI Common Toxicity Criteria (NCI-CTC) 3.0. Response to treatment was evaluated by imaging (using a combination of WHO, RECIST, modified RECIST and SUV changes) and CEA levels. Kaplan Meier methodology was employed to calculate Progression Free (PFS) and Overall (OS) Survival. Results: From September 2009-2011, 19 patients received Y90. Common complaints post treatments were: grade 1-2 fatigue and grade 1 fever, which are known side effects of SIRT. No DLTs were observed. Grade 3 hyperbilirubinemia was recorded for two patients and was attributed to progressive disease; one patient in the third cohort suffered grade 3 nausea and pain. Twelve patients (70.6%) responded (defined as stable disease or better) while five (29.4%) progressed-this was based on evaluations from initial post treatment imaging. Two patients’ imaging is pending. Median PFS and OS were 6 [95%CI: 3.2-9.7] and 16 [95%CI: 5.8-17.6] months respectively. Conclusions: It is safe to administer the entire dose of Y90 in patients with CLM who progressed despite prior pump and systemic chemotherapy. Oncologic outcomes are promising.
Use of genetic variants of LMTK3 to predict tumor recurrence in female localized gastric adenocarcinoma.
Authors: Wakatsuki Takeru , Bohanes Pierre Oliver , Zhang Wu , Gerger Armin , Yang Dongyun , Ning Yan , Winder Thomas , Labonte Melissa Janae , Wilson Peter M.D. , Benhaim Leonor , El-Khoueiry Rita , El-Khoueiry Anthony B. , Iqbal Syma , Giamas Georgios , Stebbing Justin , Lenz Heinz-Josef 
Published: February 2017

63 Background: Previous study suggests that high basal Lemur Tyrosine Kinase 3 (LMTK3) expression was associated with advanced stage of primary breast cancers as well as decreased overall and disease-free survival. LMTK3 was also found overexpressed in gastric cancer. Our previous data showed the mutant variants of two single nucleotide polymorphisms (SNPs) in LMTK3 (rs8108419 and rs9989661) were independently associated with reduced time to tumor recurrence (TTR) in colon cancer (CC). We hypothesized that LMTK3 rs808419 and rs9989661 may predict TTR in a cohort of localized gastric cancer patients. Methods: Either blood or FFPE tissue specimens obtained from 137 localized (stage Ib-IV) GA patients (54 females and 83 males) were included in this study. All patients were treated with surgery alone or surgery and adjuvant (radio)-chemotherapy at the University of Southern California/Norris Comprehensive Cancer Center (USC/NCCC), the Los Angeles County/University of Southern California Medical Center, or the Memorial Sloan-Kettering Cancer Center from 1992 to 2008. The median follow-up was 3.3 years. LMTK3 rs8108419 and rs9989661 were determined by PCR-RFLP. The primary endpoint of the study was TTR. Results: LMTK3 rs9989661 was significantly associated with TTR in females GA patients. Female patients with minor C allele (TC or CC) (n=25) of LMTK3 rs9989661 showed significantly longer median TTR=7.0 (95%CI: 2.1-8.3+) years compared to those harboring homozygous TT genotype. (n=28), TTR=1.7 (95%CI: 0.7-7.0+) years.( log-rank p=0.025; univariate analysis). After Cox proportional hazards model adjustment for stage and type of adjuvant chemotherapy, this result remained significant (HR: 0.14, 95%CI: 0.02-0.94, multivariate Wald p value = 0.043 in the dominant model). No significant association was found between TTR and LMTK3 rs9989661 in men and rs8108419 in both genders. Conclusions: This pilot study demonstrating LMTK3 rs9989661 may be potential molecular marker to predict TTR in female localized GA. Larger prospective trials are warranted to confirm these findings, and in vitro and in vivo studies are needed to identify the underlying biological mechanism.