bluuebunny/crossref_metadata_2025_split huggingface dataset:
An international patient-centered outcome measurement set for colorectal cancer.
Authors: Mamon Harvey J. , Zerillo Jessica A. , Schouwenburg Maartje Gisele , van Bommel Annelotte , Stowell Caleb , Van De Velde Cornelis J. H. , Tollenaar Rob A.E.M. 
Published: March 2017

753 Background: While there are tools to measure outcomes relevant to patients with colorectal cancer, none is universally accepted and none incorporates components of long-term clinical outcomes, acute complications, and patient-reported outcomes (PROs). Methods: The International Consortium for Health Outcomes Measurement convened an international multidisciplinary working group to develop a comprehensive patient-centered outcome measurement set for patients with all stages of colorectal cancer. The working group utilized a literature review, patient focus group and their own clinical expertise to reach consensus on outcomes and case mix factors through a modified Delphi process. Measurement tools were selected by International Society of Quality of Life Research standards. The final list of PROs was validated through a patient survey. Results: The 29 members of the working group included patient representatives and palliative care, nursing, pathology, medical oncology, colorectal surgery and radiation oncology specialists from academic and nonacademic practices in Europe, Australia, Asia and the USA. The international focus group included 11 patients with colorectal cancer treated with palliative and curative intents. The working group defined four clinical outcomes applicable to all and eight specific to subgroups, such as presence of ostomy for patients with rectal cancer and hospital admission in the last 30 days of life for patients with advanced disease. An algorithm for documenting acute complications was developed. The working group defined 11 PROs applicable to all and eight specific to subgroups, such as erectile dysfunction for patients who received radiotherapy/surgery and neuropathy for those who received chemotherapy. 276 colorectal cancer patients completed the validation survey. Conclusions: Through use of extensive patient input, the international multidisciplinary group developed a patient-centered outcome measurement set incorporating clinical outcomes, acute complications and PROs for patients with colorectal cancer. This comprehensive measurement set allows for standardized international comparison on quality of care outcomes and will be revised annually.
Bevacizumab and its impact on survival for patients receiving subsequent anti-EGFR therapy: Results from the South Australian metastatic colorectal cancer registry.
Authors: Price Timothy Jay , Karapetis Christos Stelios , Roy Amitesh Chandra , Padbury Robert , Maddern Guy , Roder David , Piantadosi Cynthia , Burge Matthew E. , Townsend Amanda Rose 
Published: March 2017

754 Background: Questions over the impact of 1st line bevacizumab on subsequent sensitivity to anti-EGFR therapy have been raised with authors hypothesizing that up-front anti-VEGF agent’s use influences biological changes that increase the risk of acquired resistance to subsequent EGFR inhibitors. Methods: Aretrospective cohort study was performed to compare the characteristics and survival of patients who were treated with an anti-EGFR therapy 2nd line and beyond by two groups defined by the 1st line therapy; 1. chemotherapy (chemo) plus bevacizumab (bev) and 2. chemo alone. Pearson chi test analysis was performed to determine whether receiving 1st line bev was associated with worse OS. Results: 348 mCRC patients who received chemo with or without bev and then an anti-EGFR therapy were studied. Patient characteristics are summarised in table. The significant differences between group 1. Vs. 2. were as follows; median age, lower use of single agent FU, KRAS status not tested, and where BRAF MT status was known (11%); BRAF MT rate. Median OS for the 2 groups was 34.2 mths, and 28.2 mths respectively (p = 0.12). Conclusions: Survival was not significantly different between the two groups, and the trend was towards higher OS with chemo plus bev suggesting that in our registry population, bev administration in first line therapy with chemo did not lead to a worse outcome for those patients subsequently receiving anti-EGFR therapy. [Table: see text]
Reinduction of oxaliplatin-based chemotherapy after exposure to oxaliplatin in adjuvant setting for colorectal cancer.
Authors: Beom Seung-Hoon , Ahn Joong Bae , Shin Sang Joon , Jung Minkyu 
Published: March 2017

755 Background: Oxaliplatin-based chemotherapy is commonly used chemotherapy in the adjuvant setting for colorectal cancer patients. In clinical practice, those patients may be retreated with oxaliplatin after relapse. The efficacy and predictive factor of oxaliplatin re-treatment are little known. Methods: We carried out a retrospective study of 53 consecutive patients who underwent surgery and adjuvant FOLFOX chemotherapy and who were re-treated oxaliplatin-based chemotherapy after relapse at Yonsei Cancer Center from April 2009 through October 2015. The main end-point was progression-free survival (PFS). Results: Among enrolled patients, 33 (62.2%) received curative resection in initially non-metastatic setting and the other 20 (37.7%) did R0 resection including metastasectomy in stage 4 at the time of previous oxaliplatin treatment. Median time from last cycle of adjuvant FOLFOX to the first cycle of palliative oxaliplatin based chemotherapy was 31.5 months. Palliative oxaliplatin was given as second and third or later in 37 (69.8%) and 16 (30.2%) patients respectively. Median PFS and overall survival (OS) were 5.1 and 17.5 months. Response rate and disease control rate to palliative oxaliplatin based treatment were 17.0 % and 66.0%. Patients with both shorter interval from first oxaliplatin exposure to recurrence (<12 months) and shorter interval from recurrence to oxaliplatin re-exposure (<18 months) experienced shorter PFS significantly compared to those who did not (2.8 vs. 7.3m, p = 0.004). It was an independent predictive factor for PFS in addition to use of targeted agent in multivaviate analysis. Conclusions: In this study, re-treatment with oxaliplatin based chemotherapy after recurrence demonstrated modest clinical efficacy. Non-use of targeted agent and both shorter interval from first oxaliplatin exposure to recurrence and shorter interval from recurrence to oxaliplatin re-exposure are poor predictive factors for PFS.
Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios as predictive and prognostic markers in patients with locally advanced rectal cancer treated with neoadjuvant chemoradiation.
Authors: Dudani Shaan , Marginean Horia , Tang Patricia A. , Monzon Jose Gerard , Raissouni Soundouss , Asmis Timothy R. , Goodwin Rachel Anne , Gotfrit Joanna , Cheung Winson Y. , Vickers Michael M. 
Published: March 2017

758 Background: A standard therapy for locally advanced rectal cancer (LARC) includes fluoropyrimidine (FP)-based neoadjuvant chemoradiation (nCRT). Previous studies have inconsistently demonstrated that baseline neutrophil- and platelet-to-lymphocyte ratios (NLR and PLR) are predictive of response to nCRT or prognostic of outcomes in LARC. Methods: We performed a review of patients with LARC undergoing nCRT followed by surgery with curative intent from 2005-2013 in 3 academic cancer centers from 2 Canadian provinces. Data regarding demographics, staging, baseline hematologic variables (<4 weeks prior/up to 2 weeks after initiating nCRT) and treatment details were collected. Outcome measures of interest were pathological complete response (pCR), disease-free survival (DFS) and overall survival (OS). Logistic regression and Cox proportional hazard models were used to assess for an association between baseline hematologic variables and outcomes. Results: Of 1081 identified patients, 845 were included in the DFS/OS analysis. Median age was 61 (range 23-87), 70% male, 85% performance status (PS) 0-1. 31% and 67% had clinical stage II and III disease, respectively. 25% had elevated NLR (≥ 4), and 64% had elevated PLR (≥ 150). 98% of patients received FP-based nCRT, with 96% receiving ≥ 44 Gy (median 50 Gy [range 20-74]). 80% completed neoadjuvant chemotherapy and 94% completed neoadjuvant radiotherapy, with a pCR rate of 23%. After a median follow up time of 64 months, 6% developed local recurrence, 20% developed distant recurrence and 19% have died. 5-year OS and DFS were 78% (95% CI 74-81%) and 76% (95% CI 73-79%), respectively. In multivariate analyses, elevated baseline NLR and PLR were not prognostic for OS or DFS. Elevated NLR was a negative predictor of pCR (OR 0.61, p=0.037, 95% CI 0.38-0.97); there was no association with elevated PLR. Conclusions: Elevated NLR was a negative predictor of pCR, but not prognostic for DFS and OS. PLR was neither predictive nor prognostic.
Chemotherapy for metastatic colon cancer: Effect on survival when the dose is reduced due to side effects.
Authors: Munker Stefan , Gerken Michael , Fest Petra , Ott Claudia , Schnoy Elisabeth , Fichtner-Feigl Stefan , Wiggermann Philipp , Vogelhuber Martin , Herr Wolfgang , Stroszczynski Chrisitan , Schlitt Hans J. , Evert Matthias , Reng Michael , Klinikhammer-Schalke Monika , Teufel Andreas 
Published: March 2017

761 Background: 5-Fluorouracil (5FU), Folinic acid (FA), and Oxaliplatin (FOLFOX) or 5FU, FA, and Irinotecan (FOLFIRI) are standard regimens for palliative chemotherapy of metastatic colon cancer. Since data showing the influence of dose reduction in palliative treatment are rare, the objective of this single center, retrospective study was to further characterize the influence of dose reduction on efficacy of these therapeutic regimens. Methods: 109 patients, diagnosed with stage IV colon cancer between 2004 and 2012 and receiving palliative first-line chemotherapy with either FOLFOX or FOLFIRI regimens in our outpatient clinic were analyzed for treatment efficacy. Patients who received dose reductions due to side effects usually received doses of 80% or lower of per protocol dose. Survival data were obtained from the Regensburg Tumor Registry. Survival analysis was performed using Kaplan-Meier statistical analysis. Results: Dose reduction was independent of age. Major reasons for dose reduction were neutropenia (30%) followed by polyneuropathy (16%) and diarrhea (14%). Dosage was more often reduced in patients receiving FOLFOX based therapy. Two-year survival of FOLFOX and FOLFIRI treated patients was comparable (35%). We observed no significant (p = 0.323) difference on two-year survival in patients receiving a reduction of chemotherapy with dose reduction (48%) compared to standard dose (31%). Further subgroup analysis did not reveal any subgroup of patients suffering from side effects with significantly worse outcome upon dose reduction. In contrast, patients who underwent dose reduction received more cycles of chemotherapy (13.7 vs. 10.8 cycles) and cumulative dosage was similar in both groups. Conclusions: A moderate reduction of chemotherapy due to side effects has no measurable effect on survival in patients with palliative colorectal cancer. This may be partially due to a longer treatment of patients with reduced chemotherapy dosage if side effects are present.
Comparison of survival for left-sided KRASwt mCRC patients treated with anti-EGFR based therapy as compared to right-sided mCRC.
Authors: Petruzelka Lubos B. , Obermannova Radka , Hejduk Karel , Ostrizkova Lenka , Zdrazilova-Dubska Lenka , Brancikova Dagmar , Bencsikova Beatrix , Vyzula Rostislav , Vocka Michal 
Published: March 2017

763 Background: Anti-EGFR-antibody-based treatment is a standard of care in patients with RASwt metastatic colorectal cancer (mCRC). Right-sided mCRC is associated with frequent presence of KRAS mutation and with worse prognosis. Here we show the clinical outcome of 1st, 2nd, and 3rd-line anti-EGFR therapy in KRASwt mCRC patients in the context of primary tumor location. Methods: Data from 3 national comprehensive cancer centers in the Czech Republic were collected prospectively from 01/2009 to 03/2016. A retrospective analysis of outcomes of 567 pts with KRASwt mCRC treated with anti-EGFR was performed. Right-sided colon was defined as coecum, ascending colon and transverse; while left-sided contains the splenic flexure, descending and sigmoid colon. The group of metastatic rectal cancer was analyzed separately. The primary objective was assessment of OS and PFS in 1st, 2nd, and 3rd-line treatment of mCRC. OS and PFS were calculated using the Kaplan-Meier method and statistical significance was assessed using the log-rank test. Results: Right-sided tumor location was in 125 pts (22.0%), left-sided in 231 (40.7%) and rectal in 211 (37.2%). Median OS and PFS in months with 95% CI and log-rank test p-value are shown in a table. Conclusions: KRASwt mCRC patients with primary tumor in left-sided colon and rectum have comparable clinical outcome when treated with anti-EGFR-based therapy. In metastatic disease, primary right-sided KRASwt carcinoma is associated with short PFS and OS across all anti-EGFR-based treatment lines. The work was partially supported by Czech Ministry of Helth project no. 16-31966A and Technology Agency of the Czech Republic no. TA04010838. [Table: see text]
Immunotherapy using activated T cells with chemotherapy for metastatic colorectal cancer.
Authors: Yoshida Yoichiro , Aisu Naoya , Nagano Hideki , Komono Akira , Kojima Daibo , Mera Toshiyuki , Tanaka Toshihiro , Naitoh Keiko , Yasumoto Kosei , Kamigaki Takashi , Goto Shigenori , Hasegawa Suguru 
Published: March 2017

767 Background: The programmed death-1 (PD-1), an inhibitory receptor expressed on activated T cells, is demonstrated to induce an immune-mediated response and play a critical role in tumor initiation and development. T cell activation induces effective antitumor immune response in cancer patients. Adoptive immunotherapy of cancer is evolving with the development of novel technologies that generate proliferation of large number of T cells. We evaluated the safety and efficacy of the combination of adoptive immunotherapy using αβ T cells with chemotherapy for metastatic colorectal cancer (mCRC). Methods: Seventeen patients with mCRC received XELOX + bevacizumab + ex vivo expanded αβ T lymphocytes as a first-line chemoimmunotherapy. Results: Median age of the 17 patients (6 men, 11 women) was 64 years (range:38–80). The T cell number was more than 5.0×109 for each infusion. Median progression-free survival was 15.2 months. Response rate was 80% (complete response (CR) = 23.5%, partial response (PR) = 47.1%, stable disease (SD) = 29.4% and progressive disease (PD) = 0%). Most adverse events were mild to moderate in intensity and immunotherapy-associated toxicity was minimal. Conclusions: Combination of adoptive αβ T cell immunotherapy with chemotherapy for mCRC is safe and effective.
A phase I/II study for panitumumab combined with TAS-102 in patients with RAS wild-type metastatic colorectal cancer (APOLLON study): Phase I results.
Authors: Kato Takeshi , Kagawa Yoshinori , Komatsu Yoshito , Oki Eiji , Yoshino Takayuki , Yamazaki Kentaro , Yasui Hirofumi , Satake Hironaga , Shibuya Kazunori , Oba Koji , Yamaguchi Kensei 
Published: March 2017

770 Background: Both panitumumab (Pmab), the anti-EGFR antibody and TAS-102, the combination drug of trifluridine and tipiracil are approved agents for the treatment of metastatic colorectal cancer (mCRC). In preclinical models, the combination of Pmab with TAS-102 demonstrated enhanced activities compared with either drug alone. This phase I/II study is designed to investigate the safety and efficacy of Pmab combined with TAS-102 in patients (pts) with RAS ( KRAS/NRAS) wild-type mCRC refractory to standard chemotherapies. Here we reported the results of phase I part. Methods: Eligible pts are aged 20-74 y, ECOG performance status (PS) 0-1 with confirmed RAS wild-type mCRC, and refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin and anti-angiogenesis therapy, and had no prior treatment with anti-EGFR antibody, TAS-102 or regorafenib. Phase I part is designed to evaluate the incidence of dose limiting toxicities (DLTs) during the first course and to determine recommended phase II dose (RP2D) in the dose de-escalation design (3 + 3 manner) of Pmab (6 mg/kg on days 1 and 15, every 4 weeks per course) combined with TAS-102 (35 mg/m2 BID on days 1-5 and 8-12, every 4 weeks). DLTs were defined as drug-related adverse events (AEs) as follows; febrile neutropenia, G4 neutropenia > 7days, G4 thrombocytopenia, inability to start the 2nd course more than 14 days delay, and G3/4 non-hematological toxicities. Results: Seven pts (3 male, 4 female) with a median age of 68 (range 57-71) were enrolled. Pts were ECOG PS 0 (3/7) or 1 (4/7) with primary tumor located in the colon (3/7) or rectum (4/7). One pt was excluded for the DLT evaluation due to protocol deviation. No DLT was observed in the 6 DLT-evaluable pts. Most frequent drug-related AEs during the DLT evaluation period were G2/3 neutropenia, G1/2 stomatitis, G1 nausea, G1 anorexia and G1/2 rash. Three pts achieved a partial response, and 3 pts had a stable disease. Conclusions: The RP2D for Pmab combined with TAS-102 was determined as the standard dose of Pmab and TAS-102. The enrollment of phase II part is ongoing to evaluate the PFS rate at 6 months by investigator assessment as a primary endpoint with the target number of 46 pts. Clinical trial information: 02613221.
Does primary site of colorectal cancer become a prognostic factor of patients undergoing curative resection of liver metastases?
Authors: Kizawa Rika , Ichikawa Yasushi , Kumamoto Fumitaka , Sawada Yu , Matsuyama Ryusei , Kobayashi Noritoshi , Goto Ayumu , Tokuhisa Motohiko , Ishibe Atsushi , Momiyama Masashi , Suwa Yusuke , Hiroshima Yukihiko , Matsuo Kenichi , Ota Mitsuyoshi , Akiyama Hirotoshi , Yamanaka Takeharu , Tanaka Kuniya , Endo Itaru 
Published: March 2017

772 Background: The comparison of prognosis between right and left-sided colon cancer (RC, LC) has recently attracted a lot of attention. We examined whether primary location of colo-rectal cancer represents a prognostic factor of patients received curative resection of liver metastasis. Methods: We reviewed all patients undergoing resection of liver metastasis of colo-rectal cancer from1992 to 2013 in the 2 YCU hospitals, and selected eligible 377 patients (59 [15.6 %] with RC, 318 [84.4 %] with LC) undergoing R0 or 1 resection of primary and metastatic lesions. Patients with transverse colon cancer were excluded. We stratified patients according to previously-reported prognostic factors of hepatic metastasis resection, and conducted univariate analysis by Log Rank test to compared overall survival (OS) in each stratum. Using those results, independent factors affecting OS were determined by multivariable Cox regression. Results: The median OS of 377 patients was 66 months, and disease free survival (DFS) was 11.6 months. Univariate analysis revealed that the number and maximum diameter of liver metastasis, existence of other metastasis apart from liver, CEA, and having pre- or post- operative chemotherapy showed significant difference of OS. Primary site did not show significant difference of OS (p = 0.547), but median OS of LC (67 months) was 24 months longer than of RC. As for DFS, there was no significant difference between RC and LC (10.75 vs. 11.6 months, p = 0.873). Multivariate Cox regression analysis was conducted using former factors showing significant difference and primary site. Then primary site was an independent prognostic factor (p = 0.047). LC showed a lower risk than RC (HR: 0.675). Conclusions: The primary site did not affect DFS, but could become a prognostic factor of OS with patients undergoing curative resection of liver metastases. It suggested that curative resection of liver metastases could contribute to prolong survival, regardless of RC or LC. And there is some possibility that the primary site affects prognosis after post-operative recurrence of colo-rectal cancer liver metastases.
Treatment strategy for colorectal liver metastases: Clinical impact of FOLFOXIRI regimen for unresectable cases.
Authors: Morine Yuji , Shimada Mitsuo , Imura Satoru , Ikemoto Tetsuya , Iwahashi Shuichi , Saito Yu , Ishikawa Daichi , Teraoku Hiroki , Yoshikawa Masato , Higashijima Jun 
Published: March 2017

780 Background: Recent advances in systemic chemotherapy, including molecular target agents, can introduce “Conversion surgery” and achieve R0 resection even for initially unresectable colorectal liver metastasis (CRLM). We investigated the optimal indication for initial surgical induction and treatment strategy for unresectable CRLM. Methods: Our current surgical indication for CRLM as follows: i) curative resection is achievable, ii) no limitation of tumor size and number, and iii) future remnant liver volume over 35%. Additionally, same indication is applied even after chemotherapy.Two hundreds forty-one cases from 1994 to 2015, consisted of 134 initially resectable case and 107 unresectable cases, were included. Among 107 unresectable cases, 55 cases received current chemotherapy such as FOLFOX, FOLFILI, XEROX and FOLFOXIRI. Results: 1) Optimal indication for initially resectable case:Multivariate analysis revealed MDN (Maximum Diameter × Number) index more than 30 of metastatic liver tumor (HR3.06), non-curative resection of metastatic liver tumor (HR4.082) and poor differentiation of primary tumor (HR11.14).2) Treatment strategy of unresectable case for “Conversion surgery” (FOLFOXIRI vs. other regimen): Forty-two unresectable cases with MDN > 30 were included. Of those 14 cases, FOLFOXIRI regimen was applied. Regarding clinicopathological factors, the use of molecular targeted drug was introduced in all patients of FOLFOXIRI group, but 67.9% patients of other regimen group. The “Conversion” rate in FOLFIXIRI group and other regimen group were 64.3% and 39.3% (p = 0.126), and median period until “Conversion” were 6.2 courses and 11.8 courses (p = 0.038). Regarding tumor necrotic rate, FOLFOXIRI regimen induced higher necrotic rate than other regimen group (77.9% vs. 50.4%, p = 0.073). Overall survival in FOLFOXIRI group has been better than that in other regimen group and 3-years survival rates were 83.3% and 48.0% (p = 0.044). Also, relapse free survival in FOLFOXIRI group was significantly better than that in other regimen group (p = 0.002). Conclusions: MDN can predict surgical outcome for CRLM. FOLFOXIRI plus molecular target drug may be a promising option for CRLM with MDN > 30.