bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repeated anti-CEA-radioimmunotherapy (RAIT) with 131iodine-labetuzumab after resection of colorectal liver metastases (CLM): Long-term results of a prospective phase II study.
Authors: Homayounfar Kia , Sahlmann Carsten O. , Niessner Martin , Meller Johannes , Conradi Lena-Christin , Dyczkowski Jerzy , Ghadimi B. Michael , Becker Heinz , Goldenberg David M. , Liersch Torsten 
Published: February 2017

719 Background: Previously, single anti-CEA-radioimmunotherapy (RAIT) with 131iodine(I)-labetuzumab after complete (R0) resection of CEA-positive CLM was well tolerated and improved overall survival (OS) compared to a control group without RAIT. In this phase II study, we examined safety, feasibility, and long-term efficacy of repeated RAIT in the same setting. Methods: After R0-resection of CEA-positive CLM, 63 pts (42 m, 21 f; median age, 64.5 yrs) with synchronous (n=33) or metachronous (n=30) CLM received RAIT with 40-50 mCi/m2 per dose. 45 pts were intermediate/high risk for early metastatic relapse according to the Fong score. Restaging with CT/MRI and FDG-PET was performed prior to each RAIT. Pts with persistent elevated serum CEA-levels or inconclusive lesions during post-operative restaging received RAIT, but were classified as “non-adjuvant.” Toxicity was classified according to NCI-CTC v2.0. Time to progression (TTP), OS and cancer-specific survival (CSS) were calculated. The median follow-up was 54 (range 6-127) mos. Results: After the first cycle of RAIT 14 of 63 pts experienced grade 4 hematological toxicity. Nineteen pts did not receive the second cycle of RAIT due to prolonged toxicity, impaired performance status (n=6), or metastatic relapse (n=13). The latter were further treated by resection (n=3) or systemic chemotherapy (n=10). Forty-four pts received the planned second cycle of RAIT. Of these, 4 pts newly experienced grade 4 hematological toxicity. For all 63 pts, the median TTP, OS and CSS were 13, 57 and 92 months, respectively. The truly “adjuvant” pts (n=39) had a an improved median TTP (26 vs. 6.6 mos, p<0.0001), OS (76 vs. 42 mos, p=0.03) and CSS (not reached vs. 42 mos, p=0.003) in comparison to “non-adjuvant” pts (n=24). Conclusions: Repeated anti-CEA-RAIT with 131I-labetuzumab is safe, feasible, and well-tolerated (100% compliance), with expected hematological toxicity. The long-term survival after RAIT is very encouraging, in particular for pts deemed truly “adjuvant” post-salvage resection of CLM at restaging prior to RAIT.
Identifying variables influencing the efficiency and efficacy of a multidisciplinary team meeting.
Authors: Basta Yara L. , Baur Onno L. , van Dieren Susan , Klinkenbijl Jean H. G. , Tytgat Kristien M. A. J. 
Published: February 2017

730 Background: Multidisciplinary team meetings (MDM) provide a platform for discussing diagnoses and treatments. Since many healthcare settings have accepted multidisciplinary care as best practice, avenues towards improving MDMs should be investigated. This study aimed to identify variables that influence the efficiency and efficacy of an MDM in a tertiary referral center in the Netherlands. Methods: Consecutive MDMs for hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), esophageal and gastric cancer (ESOGAS) and pancreatobiliary and liver cancer (HPB) were studied. Efficiency was measured as duration of the MDM. Efficacy was assessed by accurate diagnoses. Logistic and linear regression models identified variables influencing the efficiency and efficacy. Results: In 74 MDMs with a mean duration of 63 min (SD 14), 700 patients were discussed of which 114 patients at ≥2 MDMs. A median of 10 patients was discussed per MDM (IQR 6 – 14). Mean discussion time per patient was 05:19 min (SD 2). Corrected for tumor type, the number of patients discussed and the presence of others (e.g., research fellows) in addition to medical specialists, prolonged the MDM (+1.9 min CI 1.2 – 2.6; +0.64 min; CI 0.23 – 1.5 resp.). Including a follow up patient in the MDM, decreased the duration by 3.9 min (CI -5.8 – -2.0). The diagnostic accuracy of the MDM was 95%. The duration of the MDM or number of patients discussed did not influence this (OR 1.1 CI 0.99 – 1.0; OR 0.92 CI 0.79 – 1.1 resp.). The diagnosis was accurately altered for 117 (21%) patients, for 1 patient it was altered incorrectly. Tumor type predicted the accurate diagnoses (OR 0.1 CI 0.02 – 0.71; OR 2.0 CI 0.46 – 8.6; OR 3.1 CI 1.3 – 7.4; for HCC, CRC and ESOGAS respectively. Reference group: HPB). A correct diagnosis was more likely if patients’ cases were presented by their own doctor (OR 5.0 CI 2.0 – 12.5). Conclusions: MDMs play a crucial role in oncology management. For 21% of patients the diagnosis was correctly altered by the MDM. The diagnostic accuracy of the MDM was 95%. The absence of a presenting doctor decreased this accuracy while duration of MDM and number of patients discussed did not affect this accuracy. The presence of research fellows prolonged the duration of the MDM.
Prevalence and outcomes of patients (pts) with EGFR S492R ectodomain mutations in ASPECCT: Panitumumab (pmab) vs. cetuximab (cmab) in pts with chemorefractory wild-type KRAS exon 2 metastatic colorectal cancer (mCRC).
Authors: Price Timothy Jay , Newhall Kathryn , Peeters Marc , Kim Tae Won , Li Jin , Cascinu Stefano , Ruff Paul , Suresh Attili Venkatasatya , Thomas Anne , Tjulandin Sergei , Boedigheimer Michael , Zhang Kathy , Sidhu Roger , Murugappan Swaminathan 
Published: February 2017

740 Background: Mutations resistant to anti-EGFR treatment (tx), beyond those in RAS, have been reported and include EGFR S492R. We report results for pts with EGFR S492R mutations in the phase 3 ASPECCT trial. Methods: Pts were randomized 1:1 to receive pmab or cmab. Crossover was not allowed. The primary endpoint was non-inferiority of overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. EGFR S492R was evaluated by digital droplet PCR in plasma samples collected pre-tx and post-tx (safety follow-up 4 wks after the last dose). Outcomes were analyzed by EGFR S492 status. Results: Of 999 pts randomized and treated, post-tx samples were available for EGFR S492 assessment from 53% of pts (261/496) in the pmab arm and 57% of pts (285/503) in the cmab arm. EGFR S492R was detected in 1% of pts in the pmab arm and 16% of pts in the cmab arm in post-tx samples. EGFR S492R was not detected in pre-tx samples. Results are shown (table). Conclusions: In a retrospective analysis of pts with available samples from ASPECCT, 16% of pts in the cmab arm and 1% of pts in the pmab developed EGFR S492R mutations. Pts with EGFR S492R in the cmab arm had longer tx duration before progressive disease (PD) and appeared to have worse OS vs pts with wild-type S492 in the cmab arm. Clinical trial information: NCT01001377. [Table: see text]
Impact of CGA in therapeutic decisions: ELDERLY trial.
Authors: Gallego Plazas Javier , Asensio Martinez Elena , Lozano Inmaculada , Ricote Guillermo , Ore Martin , Cotes Almudena , Magdaleno Alejandra , Ors Mamen , Baron Jose M. , Campello Eric , Guaraz Patricia , Fernandez Silvia , Martinez Natividad 
Published: February 2017

759 Background: Based on results from phase III clinical trials chemotherapy treatment benefit in patients ≥70 years old with stage III and IV colorectal cancer (CRC III-IV) is a subject in question. The ELDERLY trial aims to explore in a pilot program viability and convenience of an evidence based protocol for Comprehensive Geriatric Asessment (CGA) as well as the contribution of further evaluations. Methods: Patients ≥70 years old with CRC III-IV were prospectively and consecutively included. After initial treatment recommendation was made, study protocol for CGA (functional, nutritional, cognitive, social, psychological, and comorbidities) was carried out. Based on CGA, early death risk prediction model and chemotherpy toxicity risk stratification subsequent final treatment recommendation was obtained. Follow up of patients and comparison to historical controls is underway. Results: 20 patients (10 CRC III, 10 CRC IV), median age 79.2 years (71-85), 65% males, were included. ECOG PS was: 0 in 35% of patients, 1 in 35%, 2 in 20%, and 3 in 10% of patients. Initial treatment recommendation was: standard for 60% of patients, adapted standard for 25%, and no treatment for 15% of patients. According to Köhne et al. (Oncologist 2008) fitness categories 25% of patients were in group I, 55% in group II, and 20% of patients in group III. Early death risk, according to Soubeyran et al. (J Clin Oncol 2012), was high for 5% of patients. Chemotherapy toxicity risk, according to Hurria et al. (J Clin Oncol 2011) was low for 15% of patients, intermediate for 60%, and high for 25% of patients. Final treatment recommendation was: standard for 25% of patients, adapted standard for 55%, and no treatment for 20% of patients. Initial and final treatment recommendation diverged in 55% of patients (more conservative final treatment recommendation in 45%, and more intense final treatment recommendation in 10%). Conclusions: Evidence based protocol CGA modified initial treatment recommendations. Follow up of patients and comparison to historical controls could contribute to improve the knwoledge and convenience of this and further evaluations.
Safety and efficacy of adjuvant modified FLOX for patients (pts) with stage III colorectal cancer (CRC) treated in the community.
Authors: Protasio Bruno Mendonca , Matutino Adriana Reis Brandao , Lage Liana Valente , De Santana Iuri Amorim , Ramos Ricardo Emanuel De Oliveira , Caires-Lima Rafael , Caires Inacelli Queiroz De Souza , Riechelmann Rachel Pimenta , Saragiotto Daniel Fernandes , Sabbaga Jorge , Hoff Paulo Marcelo 
Published: February 2017

760 Background: Based on the NSABP-C07 trial, FLOX became one of the standard adjuvant regimens for pts with stage III CRC. However, its efficacy and safety have not been evaluated outside of clinical trials. Methods: Retrospective analysis of all consecutive stage III CRC pts who received adjuvant chemotherapy with modified FLOX (5-FU bolus 500 mg/m2 and bolus of LV 20 mg/m2 for 6 consecutive weeks and oxaliplatin 85 mg/m2 in 2 hours-infusion at weeks 1, 3 and 5, every 8 weeks). Logistic regression (LR) multivariable models were used to identify predictors of relapse at 2 years and factors associated with grade ≥3 toxicity. Two-sided p<0.05 were significant. Results: From Feb 2007 to Oct 2013, 267 pts were eligible: median age was 59 years, 53.2% were male and 83 (32.2%) were operated emergently. Most pts (68.2%) had stage IIIB CRC, with a median of 21 (range: 1-119) lymphnodes resected. Pathology characteristics: 32 (12%) were poorly differentiated, 132 (49.4%) had angiolymphatic invasion and 75 (28.1%) had perineural invasion. Median time to chemotherapy initiation was 63 days (range: 10-188). With a median follow-up of 24 months, 67 (25.1%) pts recurred. In LR, urgent surgery (odds ratio [OR]=1.9, 95% IC: 1.03-3.49; p=0.039), angiolymphatic invasion (OR=1.99, 1.09-3.64; p=0.024), and delay/dose reduction of chemotherapy (OR=2.62; 1.45-4.72; p=0.001) were predictors of recurrence at 2 years. Any grade ≥3 toxicity occurred in 98 (36.7%) pts, with diarrhea (16.1%), and neutropenia (15.3%) being the most frequent ones. A total of 9 (3.4%) pts died from any cause within 60 days of starting modified FLOX. Age ≥65 years (OR=2.6, 1.26-5.38; p=0.01) was associated with a higher risk of grade ≥3 toxicity in LR. Conclusions: The adjuvant modified FLOX was effective in stage III CRC pts treated in the community but offered significant risk of serious toxicity and death. This regimen should be probably restricted to fit pts who are ≤65 years. Also, similar to the stage II setting, we found that stage III CRC pts whose primary tumor were ressected emergently, those with angiolymphatic invasion or who received less dose-intense chemotherapy were at higher risk of recurrence.
Phase II trial of levocetirizine with capecitabine and bevacizumab to overcome the resistance of antiangiogenic therapies in refractory metastatic colorectal cancer.
Authors: Amin Manik , Desai Monica Dandona , Sorscher Steven , Lim Kian-Huat , Wang-Gillam Andrea , Tan Benjamin R. , Picus Joel , Highkin Maureen , Lears Kimberly , Lockhart Albert C. 
Published: February 2017

763 Background: Despite clinical success of VEGF blockade in mCRC, resistance to anti-angiogenic drugs invariably develops. IL-8 and other cytokines have been implicated in resistance development to anti-angiogenic therapy. Levocetirizine is a third generation antihistamine with anti-inflammatory and IL-8 suppression properties. We conducted a phase II trial combining levocetirizine with capecitabine and bevacizumab to potentially overcome anti-angiogenic therapy resistance in patients with refractory mCRC. Methods: This was a single-center open-label prospective trial in refractory mCRC patients. Treatment consisted of oral capecitabine 850mg/m2 – 7 days on and 7 days off, IV bevacizumab 5 mg/kg every 14 days and oral levocetirizine 5 mg daily in 14 day cycles. The primary end point was PFS and secondary endpoints included ORR and tolerability. An exploratory endpoint included correlation of PFS with cytokine (IL-8 & IL-6) levels. A sample size of 36 evaluable patients could identify a median PFS of 3.4 months at a 0.05 significance level. To document cytokine changes related to levocetirizine treatment, patients were randomized to Arm A where levocetirizine was started 7 days after starting chemotherapy or to Arm B where levocetirizine was started 7 days prior to chemotherapy. For PFS determination both arms were combined for analysis. Cytokine levels were measured at baseline and with each cycle of chemotherapy (up to three cycles). Results: 43 patients were enrolled in the trial to have 36 evaluable patients. Arm A enrolled 20 patients and Arm B enrolled 23 patients. Of the patients evaluable for best response, 19 had SD and 12 had PD. Median PFS of all patients on the study was 3.4 months (ranging 0.9 to 10.6 months). Conclusions: Median PFS in the trial was comparable to and possibly better than other regimens used in the refractory setting (e.g., median PFS of 1.9 months for regorafenib). Cytokine analysis is in progress and these results and correlations with patient outcomes will be presented to assess the impact of cytokine blockade on mCRC treatment. Clinical trial information: NCT01722162.
Tumor response assessment by measuring the single largest lesion per organ in patients with advanced gastric cancer or colorectal cancer.
Authors: Kim Jung Han , Jang Hyun Joo , Kim Hyeong Su , Song Hun Ho , Zang Dae Young 
Published: February 2017

766 Background: The Response Evaluation Criteria in Solid Tumors Guidelines version 1.1 (RECIST 1.1) adopted a total of five target lesions to be measured, with a maximum of two lesions per organ. To the best of our knowledge, the criterion of two target lesions per organ in the RECIST 1.1 is arbitrary and has not been supported by any objective evidence. We hypothesized that measuring the single largest lesion in each organ (modified RECIST 1.1; mRECIST 1.1) might show almost the same response classification as measuring two target lesions per organ (RECIST 1.1). Methods: We compared tumor responses according to the modified RECIST 1.1 and RECIST 1.1 using computed tomography in patients with advanced gastric cancer (GC) or colorectal cancer (CRC) who received a first-line chemotherapy. Results: A total of 89 patients who had at least two target lesions in any organ according to the RECIST 1.1 were included: 51 with GC and 38 with CRC. Regardless of the primary sites, the number of target lesions according to the modified RECIST 1.1 was significantly lower than that according to the RECIST 1.1 (p < 0.001). The assessment of tumor responses showed a high concordance between the two criteria, with a kappa value of 0.906 (95% CI, 0.826-0.986). Only five patients (5.6%) showed disagreement in the tumor response assessment between the two criteria: 3 in GC and 2 in CRC. Four patients showed disagreement between PR and SD, and one showed disagreement between SD and PD. The overall response rates of chemotherapy, which were calculated regardless of the primary sites and anti-cancer treatment, were not significantly different between the two criteria (42.7% versus 42.7%, p = 1.0) (Table). Conclusions: The modified RECIST 1.1, with a decreased number of target lesions, was comparable to the original RECIST 1.1 in the assessment of tumor response in patients with advanced GC or CRC. Our results suggest that it may be possible to measure the single largest lesion per organ for assessing tumor response. [Table: see text]
Assessing alternative dosing strategies for granulocyte-colony stimulating factor (G-CSF) use with FOLFOX6 therapy for treatment of colorectal cancer in a prospective cohort.
Authors: Stinson Jordan , Ko Yoo-Joung , DeAngelis Carlo , Giotis Angie , Pasetka Mark 
Published: February 2017

771 Background: While clinical guidelines recommend an average of 11 injections of granulocyte-colony stimulating factor (G-CSF) per cycle of chemotherapy, few studies support alternative dosing strategies for G-CSF use by cancer type and chemotherapy regimen. Methods: From 2004 to 2013, 63 colon and 47 rectal cancer patients were recruited and monitored throughout the course of their FOLFOX6 therapy. G-CSF use was determined by a clinical pharmacist and tracked every week to ensure patients received an adequate number of injections and were compliant with each cycle. All patients received at least two cycles of G-CSF. Occurrence of neutropenia, febrile neutropenia, and thrombocytopenia were compared between patients receiving four and five injections per cycle. Results: There were 54 males and 56 females with a median age of 56. 104 patients received adjuvant chemotherapy with the remaining six being in the metastatic setting. 83 of 110 (75%) patients experienced no delays after initiation of G-CSF with 67 (61%) of those patients receiving four or five injections per cycle. The remaining 27 of 110 (25%) patients experienced a delay in treatment after at least one cycle of G-CSF completed (15 neutropenic delays, four FN delays, and 12 thrombocytopenic delays). Significantly, only seven of those 27 (26%) patients had a neutropenic delay that occurred as a result of a failed dosing strategy after G-CSF was initiated. Of these seven neutropenic delays, five (71%) were the result of a four dose injection pattern, but none were the result of the five dose injection pattern scheme. All other delays, after at least one cycle of G-CSF (74%), were caused by patients’ non-compliance The overall compliance rate with G-CSF injections was 93%. Conclusions: Only 7 of 110 (6.4%) patients experienced a G-CSF failure. It is recommended that G-CSF be administered on day 4, 6, 8, 10, and 12 of each FOLFOX6 cycle to maintain absolute neutrophil counts and prevent treatment delays.
Perioperative management of esophageal cancer surgery based on a modified ERAS protocol.
Authors: Ogata Takashi , Makuuchi Yousuke , Segami Kenki , Kawabe Taiichi , Hayashi Shigeya , Sato Tsutomu , Osaka Yoshiaki , Tatibana Shingo , Tsuchida Akihiko , Cho Haruhiko , Yoshikawa Takaki 
Published: February 2017

99 Background: We have performed perioperative management using modified ERAS protocol after esophageal cancer surgery. Our protocol includes plaque control in collaboration with dental clinic, breathing training, nutrition support for low-nutrition, preoperative oral rehydration, pain control, early mobilization, early enteral nutrition and intestinal peristalsis monitoring by abdominal Xp with contrast agents after surgery, and so on. Methods: The aim of the study is to clarify the safety of our modified ERAS protocol as perioperative management of esohphageal surgery. 136 cases of thoracic esophageal cancer patients were performed with 3 field lymph node dissection between January 2011 and July 2014 using modified ERAS protocol(group A). 29 cases were performed classical postoperative management between September 2008 and November 2009(group B). We compared ventilator weaning dates, start dates of postoperative ambulation, start dates of enteral feeding, start dates of oral intake, length of hospital stay, the number of hospital death between group A and group B. Results: In group A, except two cases was extubated in POD1, start dates of postoperative ambulation was POD1(median), start dates of enteral feeding was POD1(median), start dates of oral intake was POD6(median), length of hospital stay was 15days(median), and the number of hospital death was 1case. On the other hand, in group B, dates of extubation was POD4(median), start dates of postoperative ambulation was POD2(median), enteral feeding was not sued for postoperative management, start dates of oral intake was POD15(median), length of hospital stay was 29days(median), and the number of hospital death was 2case. After introduction of this protocol, all these values were significantly reduced in group A rather than in group B. Walking distance were 130m(POD1), 322m(POD2), 509m(POD3), completion rate of enteral feeding was 90%, and the safety of enteral nutrition was also confirmed by peristalsis monitor using abdominal Xp with contrast agents or defecation state. Conclusions: It was considered that perioperative management of esophageal cancer surgery based on modified ERAS protocol is contribute to the early recover of postoperative status.
Sensitivity of cytology and immunohistochemistry for diagnosis of pancreaticobiliary cancer.
Authors: Burnett Atuhani S. , Bailey Joanelle , Oliver Joseph B , Ahalawat Sushil , Chokshi Ravi J. 
Published: February 2017

TPS490 Background: Biliary strictures present a diagnostic challenge to differentiate benign disease from hepatopancreaticobiliary (HPB) malignancies. ERCP cytology is commonly performed in these patients; however, its sensitivity for diagnosis of HPB malignancy is poor (41.6%). Many adjunctive tests have been investigated to improve the sensitivity of HPB biopsies. In a recent meta-analysis by our group the best immunohistochemical (IHC) stains were a combination of IMP3, S100A4, and standard cytology. IHC stains for S100P and pVHL negativity were also helpful. Based on this meta-analysis we have designed a retrospective analysis of old cell block specimens to demonstrate the sensitivity and specificity of a combination IHC staining panel in detecting HPB maliganancies. Methods: Retrospective IHC staining will be carried out on old cell blocks from ERCP brushings and EUS-FNA. Expression of IMP3, S100A4, S100P, and pVHL will be determined. Using this panel as a combination we will determine its sensitivity and specificity on 200 patient samples. We will further determine how many stains are necessary to achieve maximum sensitivity by subtraction of data from one or more IHC stains followed by repeating sensitivity calculations. Finally, we will calculate the cost of conducting these tests and determine the cost-benefit ratio of employing these tests in the wider clinical setting. Conclusions: Overall we feel these studies will advance the precision with which clinicians can determine the presence of HPB malignancy in patients undergoing biopsy. This will ultimately lead to fewer patients with benign disease undergoing resection unnecessarily.