bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ten-year survival data following resection of locally recurrent rectal cancer (LRRC).
Authors: Cyr David Patrick , Zih Francis Si Wai , Swett-Cosentino Jossie , Luu Shelly , Wells Bryan J , Burkes Ronald L. , Cummings Bernard , Esmail Faryal , Smith Andrew J , Swallow Carol Jane 
Published: March 2017

730 Background: The ‘Beyond TME’ Collaborative identified LRRC as a complex problem requiring multidisciplinary consultation and specialized surgical care. Aggressive en bloc resection of LRRC at specialized cancer centers is associated with 5y survival rates of 25-50%. However, skepticism persists that LRRC can be cured given the lack of published longer-term survival data. We investigated the oncologic outcomes at 10y following resection of LRRC and sought relevant clinicopathologic prognostic variables. Methods: The study cohort consists of 52 consecutive patients (31M, 21F) who underwent LRRC resection at our center between 09/1997 and 08/2005. En bloc sacrectomy was performed in 30 patients (58%) with the goal of achieving complete margin negative (R0) resection. At the time of LRRC resection, 46 of 52 patients had isolated LRRC (M0), and 6 had potentially resectable distant metastasis (M1). Patients were followed with H&P, CT-CAP q4mos X2y, q6mos X3y, then annually. Results: At last follow-up (f/u), 32 patients had died of rectal cancer, 1 died of other causes, 4 were alive with rectal cancer, and 15 (30%) were alive cancer-free. For the entire cohort of 52 patients, median f/u time was 44mos (4-162) and overall survival (OS) was 42% at 5y, 37% at 10y, median 43mos. In the group who were alive at last f/u (N = 19), median f/u time was 123mos (45-162). Prognostic variables for OS in univariate analysis included: m status, resection margin status, receipt of systemic Rx, and receipt of radiotherapy. All patients who had M1 disease at the time of LRRC resection died of recurrent cancer at a median of 21mos (4-46). In the 46 M0 patients, OS was 47% at 5y, 42% at 10y, median 50mos; furthermore, disease-free survival (DFS) was 38% at 5y, 38% at 10y, median 39mos. In patients who had R0 resection (n = 41), OS was 51% at 5y, 45% at 10y, median 72mos. Preoperative chemotherapy at the time of primary presentation (n = 26) or before resection of LRRC (n = 20) was associated with significantly improved prognosis ( p= 0.004, p= 0.03, respectively). Conclusions: Complete resection of LRRC was associated with durable survival in approximately 40% of patients, with plateauing of survival curves after 5y. Preoperative therapy of LRRC may improve survival.
Retrospective analysis of the effects of systemic chemotherapy to the ovarian metastases from colorectal cancer.
Authors: Sekine Katsutoshi , Hamaguchi Tetsuya , Shoji Hirokazu , Nakamura Shoko , Miyamoto Takahiro , Takashima Atsuo , Honma Yoshitaka , Iwasa Satoru , Kato Ken , Takahashi Kenta , Kato Tomoyasu , Kanemitsu Yukihide , Boku Narikazu 
Published: March 2017

731 Background: Ovarian metastases from colorectal cancers are relatively rare. Since most ovarian metastases are also associated with other metastatic sites, the prognosis is reported to be poor. It is not fully understood whether the response to systemic chemotherapy of ovarian metastases differs from that to other metastatic sites. Methods: We retrospectively reviewed the clinical data of patients with ovarian metastases from colorectal cancer treated at our hospital between January 2006 and December 2015. Results: Among the 635 female patients with relapsed or metastatic colorectal cancer, 57 (9.0%) had ovarian metastases before the first-line treatment; 37 patients received palliative chemotherapy, and 20 patients were initially treated by surgical resection. In addition, 38 cases of ovarian metastases developed after the initiation of first-line chemotherapy. Overall, 95 patients (15.0%) with ovarian metastases were treated during this period. The objective response rate for systemic chemotherapy of ovarian metastases was lower than that for other metastatic sites (22.9 % vs 60.9 % for first-line, 3.4 % vs 13.6 % for second-line, 11.1 % vs 26.6 % for third-line, and 0% vs 18.2 % for fourth-line, respectively). After the initiation of chemotherapy, surgical resection of ovarian metastases was positively associated with a longer overall survival (26.8 months for cytoreductive surgery and 17.0 months for only systemic chemotherapy, p < 0.001), especially when the other metastatic sites had not progressed after chemotherapy. Conclusions: Ovarian metastases are less responsive to systemic chemotherapy compared to the extra-ovarian metastases. Our data also suggest that multi-disciplinary treatment strategy including systemic chemotherapy and cytoreductive surgery might improve the prognosis of ovarian metastases.
Demographic and clinical characteristics of patients with metastatic colorectal cancer (mCRC) associated with RAS testing from 129 million covered lives.
Authors: Bach Bruce A. , Christodoulopoulou Alexandra , Klink Andrew , Hechmati Guy , Mujumdar Urvi , Feinberg Bruce A. , Fakih Marwan 
Published: March 2017

739 Background: Guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) recommend that all tumors be tested for RAS mutations to identify patients who will most benefit from chemotherapy regimens with biologic agents. The aim of this study was to describe characteristics of patients captured by a large national health claims database who were tested vs those who were not tested for RAS mutations and to identify potential predictors of RAS testing. Methods: Patients with mCRC diagnosed from 2012–2014 (ICD-9 codes 153.x, 154.0x, or 154.1x and 197.x–198.x) were identified from a US healthcare claims database consisting of 129 million unique covered patient lives. Patient demographics and baseline clinical characteristics were compared between patients who were and were not tested for RAS mutations (identified by CPT codes) using chi-square and t-tests. Odds ratios (ORs) were estimated for potential predictors by fitting multivariate logistic regressions to adjust for patient characteristics. Results: Of the 4,527 mCRC patients identified (mean age at diagnosis, 61.2 years; 54% male); 39% (n = 1,787) had a claim for RAS testing during the study period. Patients tested had similar mean age and comorbidity index at diagnosis compared to those not tested (60.8 vs 61.5 years, P = 0.06; 3.98 vs 3.90, P = 0.47). A greater proportion of RAS-tested patients were commercially insured compared to those not tested (37% vs 26%, P < 0.01). Adjusted for other patient characteristics, patients with commercial insurance (OR: 1.62 [95% confidence interval–CI: 1.41–1.87]), metastases to viscera (OR: 1.61 [95% CI: 1.42–1.84]), or diagnosis of colon primary site compared to rectum (OR: 1.32 [95% CI: 1.16–1.51]) had increased odds of receiving RAS testing; all P < 0.01. Conclusions: These observational data show that mCRC patients with commercial insurance, metastases to viscera, and colon cancer have a higher probability of being tested for RAS mutations. Overall, the data suggest that RAS status is underdetermined, with certain subgroups appearing to be more likely to be tested than others.
Role of systemic immune-inflammatory index, tumor infiltrating neutrophils and PD-1+ T cells to predict the postoperative recurrence after S-1 adjuvant chemotherapy for gastric cancer: A retrospective study.
Authors: Tanaka Hiroaki , Tamura Tatsuro , Hiramatsu Soichiro , Muguruma Kazuya , Miki Yuichiro , Shibutani Masatsune , Yamazoe Sadaaki , Kimura Kenjiro , Nagahara Hisashi , Toyokawa Takahiro , Amano Ryosuke , Maeda Kiyoshi , Hirakawa Kosei , Ohira Masaichi 
Published: March 2017

74 Background: The adjuvant chemotherapy with S-1 is the standard treatment for Stage II/III gastric cancer in Japan. Immunological status of host is critical for treatment outcome. Several investigators showed that systemic immune-inflammaotry indexes including neutrophil lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) well reflected the tumor progression. Methods: We analyzed clinical data obtained from 170 patients with pathological stage II/III gastric cancer who underwent surgery followed by S-1 adjuvant chemotherapy at Osaka City University Hospital between 2006 and 2015. Tumor infiltrating cells were detected by immunohistochemistry. Results: We found recurrent diseases in 70 (41%) patients including 15 in stage II and 55 in stage III. In univariate analysis using Cox proportion model, 2 grade of mGPS, the increase value of post-operative CEA, CA19-9, number of lymphocytes and NLR were associated with recurrence. Post-operative elevation of CEA and NLR were identified as independent risk factors for recurrence in multivariate analysis. Increase value of pre-operative NLR and CEA was significantly associated with early recurrent within one year after surgery. Tumor infiltrating neutrophils and PD-1+ T cells had correlated with the increase of pre-operative NLR and CEA value, respectively. Patients with low PD-1+T cells and low neutrophils had better prognosis than those with high infiltration. Conclusions: Post-surgical elevation of CEA and NLR value were useful as a predictive marker for recurrence in patients treated with S-1 adjuvant chemotherapy after surgery for gastric cancer. Early recurrence had correlated with tumor infiltrating neutrophils and PD-1+T cells. Our results suggested that systemic and local immune suppression should be an important element to exacerbate prognosis after chemotherapy for resectable gastric cancer.
Overall survival of elderly metastatic colorectal cancer patients treated in second and third line by tumor site.
Authors: Luhn Patricia , Cha Edward , Hsieh Angela Fu-Chi , Taylor Michael , Grossman William 
Published: March 2017

742 Background: The anatomical side of the colon where a tumor arises has been shown to be prognostic in patients treated with first-line therapy; patients with tumors that arise from the left side of the colon have significantly longer survival compared with patients whose tumors arise from the right side of the colon. However, there is little evidence of whether this factor is prognostic in later lines of treatment. The objective of this study was to determine the impact of tumor side on the survival of metastatic colorectal cancer patients who received second line (2L) or third line (3L) therapy. Methods: Metastatic (stage IV) colorectal cancer patients in the Surveillance, Epidemiology, and End Results (SEER) database linked to Medicare claims diagnosed 2001-2005 who received 2L (n = 921) or 3L (n = 502) therapy were included in the study. Overall survival (OS) was determined from the start of the indicated line of therapy and was estimated using the Kaplan-Meier method; statistical differences were tested using the log-rank tests. Results: The distribution of tumor sites was similar for 2L and 3L treated patients (right: 36%; left: 58%; transverse: 6%; for 2L). The median follow up time from start of therapy was 11 months (mo) for 2L and 10 mo for 3L patients. Median OS for left-sided tumors receiving 2L+ therapy was 13.6 mo (95%CI: 11.9, 14.8) compared with 8.7 mo (95%CI: 7.5, 9.9) for right-sided tumors (log-rank p < 0.001). Similar results were seen in patients receiving 3L+ therapy, although the difference was of lesser magnitude. The median OS for patients with left-sided tumors was 10.8 mo (95%CI: 9.6, 12.9) compared with 7.6 mo (95%CI: 5.7, 9.4) for right-sided tumors (log-rank p = 0.002). Conclusions: These results suggest that side of tumor origin remains a prognostic factor for colorectal cancer patients treated in later lines of therapy (2L+).
Fast track multidiscipline treatment versus conventional treatment for colorectal cancer: The results of a prospective randomized controlled study (FTMDT trial).
Authors: Ding Ke-Feng , Li Jun , Zhou Jiao-Jiao , Kong Xiang-Xing , He Jin-Jie , Yuan Ying , Yan Min , Chen Rong , Huang Xue-Feng , Chen Gang , Ying Xiao-Jiang , Dai Xiao-Yu , Li Gen-Hai , Zhang Su-Zhan , Zheng Shu 
Published: March 2017

743 Background: Fast Track Multi-Discipline Treatment (FTMDT) integrates fast-track perioperative treatment (laparoscopic or open surgery) plus XELOX adjuvant chemotherapy for colorectal cancer (CRC). This study aimed to verify the effects of FTMDT model and to clarify the value of laparoscopic surgery in fast-track perioperative treatment. Methods: The study (NCT01080547) was a prospective randomized controlled multi-centers study. Group I (FTMDT) received fast-track treatment plus XELOX chemotherapy (Group Ia received laparoscopic surgery and Group Ib received open surgery). Group II (conventional treatment, CT) received conventional treatment plus mFOLFOX6 chemotherapy (Group IIa received laparoscopic surgery and Group IIb received open surgery). The primary endpoint was total hospital stays during treatment. The secondary endpoints included surgical complications, chemotherapy related adverse events, quality of life and hospitalization costs. Results: Between April 2010 and June 2014, 374 patients were enrolled and 342 patients were finally analyzed. The total hospital stays were shorter in FTMDT than CT (median 13 days vs. 23.5 days, P= 0.0001) but similar between Group Ia and Group Ib (median 13 days vs. 14 days, P= 0.1951). The postoperative hospital stays were shorter in FTMDT than CT (median 6 days vs. 9 days, P= 0.0001) but similar between Group Ia and Group Ib (median 6 days vs. 6 days, P= 0.2160). Resume of flatus and defecation was earlier in FTMDT ( P< 0.05) and Group Ia was the earliest. The in-hospital complication rate was lower in FTMDT (6.40% vs. 14.71%, P= 0.014) but similar between Group Ia and Group Ib. The surgery cost of Group Ib was the lowest ( P< 0.05). The rate of chemotherapy related adverse events was similar between FTMDT and CT( P> 0.05). The EORTC QLQ-C30 physical functioning and fatigue in one week postoperative were better in FTMDT than CT( P< 0.05). Conclusions: FTMDT model enhanced the postoperative recovery of CRC patients. On the premise of fast-track perioperative treatment, laparoscopic surgery showed minor advantage over open surgery which had economic advantages. Clinical trial information: NCT01080547.
Phase I/II trial of dose reduced capecitabine in elderly or frail patients with untreated advanced colorectal cancer.
Authors: Breadner Daniel Adam , Welch Stephen , Jonker Derek J. , Klimo Paul , Cripps M. Christine , Biagi James Joseph , Lam Wendy , Whiston Frances , Stitt Larry , Vincent Mark David 
Published: March 2017

745 Background: Capecitabine (Cape) was initially assessed at a dose of 2500 mg/m2 in young or robust patients that do not represent the population in which oncologists consider Cape monotherapy in advanced colorectal cancer (aCRC). In practice Cape is frequently given to elderly or frail patients at 2000 mg/m2 but the optimal dosing remains controversial. Methods: A multi-centered phase I/II trial of reduced dose Cape 2000 mg/m2 d1–14 q21d was conducted in 221 patients in one or more of the following subsets: age65 years (167 pts), ECOG PS 1 (139 pts), elevated LDH (105 pts), prior pelvic RT (54 pts). Results: Median age was 72 years. A median 5 and mean 8 cycles were given (range 0 to 50). The phase I portion of the study determined prior pelvic radiation required dose reduction to 1500 mg/m2 for diarrhea. Grade 3/4 toxicity occurred in 25% of patients during the first 3 cycles (8.1% hand-foot syndrome, 7.7% diarrhea). Dose reductions were required in 14% and dose delays in 21%. Response rate is 13.6%, with 69.7% disease control rate. Median PFS was 5.6 months. Post progression 125 patients (67%) received further chemotherapy, 56 received further Cape monotherapy with a median of 4 additional cycles. Median overall survival for all patients is 14.3 months. Median survival was significantly higher for baseline ECOG 0 vs. ≥ 1 and normal vs. elevated LDH. When comparing patients receiving 2000 compared to 1500 mg/m2 the ORR was 19% vs. 17%, and the DCR was 73% vs. 63%. Median PFS was 5.9 vs. 4.7 months, and the OS was equal at 14.3 months. Hand-foot syndrome was more common at the higher dose, 46% vs. 30%, any grade. Conclusions: This report suggests dose reduced Cape has less toxicity compared to full dose, with only a small tradeoff in efficacy seen as a lower ORR. However, its improved tolerability likely leads to an increased number of cycles of therapy, and the PFS seems consistently higher at the lower dose. This trial reduces uncertainty regarding further dose reductions to 1500 mg/m2 for frail patients, in whom quality of life may be paramount. This should be viewed as compelling evidence, in the absence of a head to head clinical trial, that 2000, or even 1500, mg/m2 is an appropriate dose in elderly or frail patients with aCRC.
Hepatic artery therapies for unresectable colorectal liver metastases: Pooled survival analysis of 968 patients from TACE, yttrium-90, and HAI studies.
Authors: Moutinho Vitor , Connell Louise Catherine , D'Angelica Michael Ian , Kemeny Nancy E. 
Published: March 2017

747 Background: Approximately 140,000 people are newly diagnosed with colorectal cancer (CRC) annually, while 50,000 will die from the disease. Median survival has increased with use of modern chemotherapy and biologic agents. Sixty percent of advanced CRC patients (pts) present with or develop liver metastases, with additional treatment options such as hepatic artery therapies. However, there is no strong scientific evidence to support the use of transarterial chemoembolization (TACE), Yttrium 90 (Y90) or chemotherapy infusion (HAI). Methods: Pooled survival analysis of 968 pts with unresectable colorectal liver metastases (CLRM) treated with hepatic artery therapies, including HAI, Y90 or TACE. A rigorous selection of studies was conducted to ensure exchangeability across studies and adequate comparison of groups. Kaplan Meier survival curves were reconstructed from original publications. Data was further stratified into presence or absence of extra-hepatic disease (EHD). Results: Total of 968 pts with mean age 60.5 years, 65.5% male, 64.9% ECOG 0 and 42.4% with EHD. Patient characteristics in the various studies as per Table. Initial analysis showed a significant reduction in the hazard of death comparing HAI & Y90 (HR = 0.45[0.38, 0.55]). There was a 67% reduction in the hazard of death comparing HAI to TACE (HR = 0.33[0.27, 0.41]). Median survival in pts without and with EHD was 32 &16 months for HAI, 11 & 6 months for Y90 and 11 & 8 months for TACE (p < 0.0001). Conclusions: Based on our analysis, HAI offers better survival rates when compared to TACE and Y90. This survival advantage for HAI is not only limited to CRC pts with hepatic disease only, but also is evident in those pts with unresectable CLRM in the setting of co-existent EHD. [Table: see text]
Role of cetuximab in conversion therapy in advanced KRAS WT colorectal cancer with liver limited disease: A systematic review and meta-analysis.
Authors: McMullen Michelle , Davidson Andrew , Khattak Muhammad Adnan 
Published: March 2017

748 Background: Majority of advanced colorectal cancer (CRC) patients with liver limited disease (LLD) that undergo curative partial liver resection relapse within 5 years. Peri-operative chemotherapy is currently utilized, however the benefit of this is modest only. The addition of anti-EGFR therapy with cetuximab to chemotherapy has consistently demonstrated improvements in objective response rate (ORR) but its impact on potentially curative R0 resection, progression free survival (PFS) and overall survival (OS) remains debatable. The aim of this study was to evaluate the evidence for the use of cetuximab with chemotherapy, in the peri-operative setting for patients with advanced KRAS-WT CRC and unresectable LLD. Methods: Comprehensive literature search was conducted using PubMed and MEDLINE. Inclusion criteria identified studies evaluating the efficacy of chemotherapy and cetuximab vs. chemotherapy alone in advanced KRAS-WT CRC with unresectable LLD. Phase II studies evaluating chemotherapy-cetuximab without control arms were also included. Pooled data was included in meta-analysis and analysed using the Stata v.7. The primary endpoint was the R0 resection rate. Secondary endpoints were ORR, PFS and OS. Results: 5 trials, describing a total of 617 patients, were included in the analysis1–5. Patients receiving cetuximab in addition to chemotherapy were more likely to achieve R0 resection than patients receiving chemotherapy alone (OR 2.13; 95% CI 1.23-3.68, p < 0.05). Patients on cetuximab had improved ORR compared to patients not on cetuximab (OR 2.59; 95% CI 1.74-3.87, p < 0.05). Patients receiving cetuximab had a mean PFS 3.1 months higher than patients not on cetuximab (95% CI 2.76-3.45, p < 0.05). Patients on cetuximab also had a mean OS 0.67 months longer than those not on cetuximab (95% CI 0.44-0.91, p < 0.05). Conclusions: The addition of cetuximab to chemotherapy in the treatment of advanced KRAS-WT CRC with unresectable LLD leads to better outcomes compared to chemotherapy alone.
Aflibercept (Z) in combination with FOLFIRI for second-line treatment of patients (pts) with metastatic colorectal cancer (mCRC): Safety and quality of life (QoL) data from the Spanish subgroup of the Aflibercept Safety and Quality-of-Life Program (ASQoP).
Authors: Rivera Fernando , Polo Marques Eduardo , Aranda Enrique , Fernandez-Martos Carlos , La Casta Munoa Adelaida , Guillen Carmen , Lopez Rafael , Gil Silvia , Lema Laura , Aparicio Jorge , Martinez Villacampa Mercedes , Pisa Aleydis , Borrega Pablo , Lopez-Vivanco Guillermo , Garcia Alfonso Pilar 
Published: March 2017

751 Background: In the VELOUR trial, adding Z to FOLFIRI improves OS, PFS and RR in mCRC pts progressing after oxaliplatin ±biologic agents. The ASQoP trial (NCT01571284) was designed to gather safety and QoL data from mCRC in real-life setting. We report data collected by the Spanish investigators. Methods: ASQoP is single-arm, open-label trial evaluating safety and QoL of Z in mCRC pts as 2nd line. Eligible pts received Z (4mg/kg) q2wks on day 1/cycle, followed by FOLFIRI (dosing was at physician’s discretion) until disease progression, unacceptable toxicity, death, or investigator/pt decision. The EQ-5D was used for utility index (UI) measure and the EORTC QLQ-C30 as generic cancer instrument. QoL population consisted of pts completing the questionnaire at baseline and ≥1 assessment post-baseline and received ≥1 part of 1 dose of study treatment. Results: The safety population comprised 77 pts with ≥1 completed cycle of treatment. Grade (G)3/4 AEs were reported in 72.7% of pts (vs 83.5% in VELOUR), being G3 most commonly reported. There was no G4 hypertension, stomatitis, or proteinuria. G4 Diarrhea was found in 1.3% of pts. Mean baseline UI was 0.7 (95% CI, 0.63-0.78) in 51 pts, and remained relatively stable at cycles 3 (n=39) and 7 (n=24), with a mean (±SD) change from baseline of 0.03 (±0.26) and -0.06 (±0.35), respectively. Mean baseline global health status score was 63.1 (95% CI, 55.8-70.4) in 54 pts, and remained stable up to cycle 9 with a mean (±SD) change from baseline of 4.17 (±38). Conclusions: Thisanalysis has identified no new safety signals and suggests an acceptable toxicity profile with a relatively stable UI and QoL in Spanish mCRC pts in the real-life setting. [Table: see text]