bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral adjuvant chemotherapy using uracil-tegafur (UFT) with leucovorin (LV) after resection of colorectal cancer liver metastases: Long-term survival results of the phase III UFT/LV study.
Authors: Hasegawa Kiyoshi , Saiura Akio , Takayama Tadatoshi , Miyagawa Shinichi , Yamamoto Junji , Bandai Yasutsugu , Teruya Masanori , Yoshimi Fuyo , Kawasaki Seiji , Koyama Hiroto , Oba Masaru , Takahashi Michiro , Yamashita Suguru , Mizunuma Nobuyuki , Matsuyama Yutaka , Watanabe Toshiaki , Makuuchi Masatoshi , Kokudo Norihiro ,   The UFT/LV Study Group
Published: March 2017

672 Background: Surgical resection has been accepted as the standard therapy for colorectal cancer liver metastases (CRLM), however, high recurrence incidence even after curative resection remains a severe problem. The 1st analysis of the UFT/LV trial showed that oral UFT/LV for 6 months significantly prolonged relapse-free survival (RFS) after resection for CRLM (Kobayashi A et al. ASCO 2014, Hasegawa K et al. PlosOne 2016 E-pub). To further evaluate the impact of the UFT/LV therapy on overall survival (OS), we performed the 2nd analysis under longer follow-up period, as have been scheduled by the protocol. Methods: Patients undergoing curative resection of CRLM were randomly assigned to either UFT/LV or surgery alone (control) group. In the UFT/LV group, 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75 mg/day for 28 days followed by 7 days rest in one cycle) were administered. Results: Between 2004 and 2010, a total of 180 patients were enrolled to this trial, among whom 3 patients were ineligible for analysis. Median follow-up of the 2nd analysis was 6 years. The 5y-OS rate in the UFT/LV group was 65.3%, which was slightly better than the control group (62.2%) without statistical significance. The hazard ratio for death in the UFT/LV relative to the control was 0.86 (95% confidence interval: 0.54-1.38, P = 0.54). The OS curves of the 2 groups were identical within 4 years after resection, however, the OS curve of the UFT/LV group seemed to go higher than the control group. The 5y-RFS rate in the UFT/LV group was 36.2%, which was significantly better than that in the control group (32.3%), as have been shown by the 1st analysis. Conclusions: The results of the 2nd analysis suggested that oral UFT/LV adjuvant chemotherapy might be also useful to prolong OS, as have been confirmed for RFS. This regimen can be recommended as an alternative choice after hepatic resection for CRLM. Clinical trial information: C000000013.
Pertuzumab + trastuzumab for HER2-amplified/overexpressed metastatic colorectal cancer (mCRC): Interim data from MyPathway.
Authors: Hurwitz Herbert , Raghav Kanwal Pratap Singh , Burris Howard A. , Kurzrock Razelle , Sweeney Christopher , Meric-Bernstam Funda , Vanderwalde Ari M. , Spigel David R. , Bose Ron , Fakih Marwan , Swanton Charles , Guo Shuangli , Bernaards Coen , Beattie Mary Stanley , Sommer Nicolas , Hainsworth John D. 
Published: March 2017

676 Background: Among recent advances in precision medicine, HER2 has emerged as a potential therapeutic target for advanced colon cancer. MyPathway is a multi-basket study evaluating the efficacy and safety of targeted therapies in non-indicated tumor types harboring relevant genetic alterations. We present updated data for an expanded cohort of patients with HER2-amplified/overexpressed mCRC receiving HER2-targeted therapy with pertuzumab + trastuzumab. Methods: MyPathway (NCT02091141) is a multicenter, open-label, phase IIA study. Patients in this analysis had treatment-refractory HER2-amplified/overexpressed mCRC by gene sequencing, FISH, or IHC. Patients received standard doses of pertuzumab + trastuzumab until disease progression or unacceptable toxicity. The primary endpoint is investigator-assessed overall response rate. The cutoff date was July 31, 2016. Results: Of 34 patients with mCRC enrolled, 32 have had ≥1 tumor assessment. At a median follow-up of 5.2 (range 0.7–18.3) months from treatment initiation, 12 patients had partial responses (PR), with stable disease (SD) for >4 months in 3 additional patients (Table). The safety profiles were consistent with the product labels. Conclusions: Interim data show that HER2-targeted therapy with pertuzumab + trastuzumab, a chemotherapy-free regimen, is active in heavily pretreated HER2-amplified/overexpressed mCRC. The ORR was 37.5%, responses were durable (median 11.1 months), and the CBR was 46.9%. Accrual to MyPathway is ongoing. Clinical trial information: NCT02091141. [Table: see text]
BBI608-224: A phase Ib/II study of cancer stemness inhibitor napabucasin (BBI-608) administered with panitumumab in KRAS wild-type patients with metastatic colorectal cancer.
Authors: Larson Tim , Ortuzar Waldo Feliu , Bekaii-Saab Tanios S. , Becerra Carlos , Ciombor Kristen Keon , Hubbard Joleen Marie , Edenfield William Jeffery , Shao Spencer H. , Grothey Axel , Borodyansky Laura , Xu Bo , Li Wei , Li Youzhi , Li Chiang , Khan Waheed 
Published: March 2017

677 Background: Napabucasin a first-in-class cancer stemness inhibitor in clinical development, suppresses cancer stemness by targeting Stat3-driven gene transcription. Preclinically, potent and broad-spectrum anti-cancer activity was observed in vitro and in vivo, alone and in combination with other agents. In a phase 1 study, napabucasin monotherapy was well tolerated with encouraging signs of anti-tumor activity at the RP2D of 500 mg BID. Methods: The current open-label, multi-center study includes phase II expansion in pts with refractory, K- Raswt mCRC to confirm safety and anti-tumor activity of napabucasin administered orally at 480mg BID in combination with panitumumab (6mg/kg bi-weekly). Results: 72 pts were enrolled, 48 pts were evaluable by RECIST of which 7 (15%) and 41 (85%) had 2 or >3 prior treatment lines, respectively. Of the 48 evaluable pts, 64.6% (31/48) were previously treated with an anti-EGFR agent. No new adverse events (AEs) were observed and most common AEs included grade 1/2 diarrhea, nausea, abdominal cramps, and vomiting. Among 48 pts enrolled who received RECIST evaluation, Disease Control Rate (DCR) was observed in 25 pts (52.1%) of which 3 pts achieved PR (6%) and 22 pts achieved SD (45%). Among 31 pts previously treated with anti-EGFR therapy, DCR was observed in 15 pts (48%) compared with DCR of 59% observed in 10 out of 17 anti-EGFR naïve pts receiving a scan. Conclusions: This phase II study confirmed that napabucasin can be safely combined with panitumumab at full dose and shows encouraging anti-tumor activity in pts with K- Ras wt mCRC, regardless of prior anti-EGFR exposure, suggesting that napabucasin may sensitize pts to repeat anti-EGFR therapy. Clinical trial information: NCT01776307. [Table: see text]
Evolution in multimodality management of locally advanced rectal cancer.
Authors: Roxburgh Campbell SD , Strombom Paul , Lynn Patricio B , Cercek Andrea , Saltz Leonard , Gollub Marc Jeffrey , Crane Christopher H , Wu Abraham Jing-Ching , Shia Jinru , Vakiani Efsevia , Smith Jesse Joshua , Temple Larissa K. F. , Nash Garrett Michael , Guillem Jose G. , Paty Philip , Garcia-Aguilar Julio , Weiser Martin R. 
Published: March 2017

684 Background: This study reports the evolving multimodality management of locally advanced rectal cancer (LARC) and associated outcomes at a high volume center. Methods: Patients with Stage II/III LARC <15cm from the anal verge evaluated by the colorectal surgery service were identified from a prospective database. Clinical management including neoadjuvant therapy (NT) and surgical treatment along with pathologic and perioperative outcomes were collected. Results: Between June 2009 and March 2015, 798 patients were evaluated and received NT for LARC. Majority were staged cT3/T4 (84%) or cN+ (78%), and 635 had surgery within 26wks following NT. Reliance on MRI staging increased from 57% to 98% during the study period (P < 0.001). There was increased usage of total NT (NEO) with pre-op chemotherapy (CT) and chemoradiotherapy (CRT) (17% to 76%, p < 0.001) with a concomitant decrease in use of CRT alone (77% to 16%, p < 0.001) and post-op CT (70% to 15%, p < 0.001). The proportion undergoing surgery beyond 8wks after NT rose from 41% to 62% (P < 0.001) and beyond 8 wks after CRT rose from 45% to 72% (p < 0.001). The percentage of patients not undergoing resection by 26wks (nonoperative management) rose from 12% to 27%, P < 0.001). Minimally invasive surgery (MIS) increased from 33% to 71% (P < 0.001); in 2014-15 98% of MIS was robot-assisted. Over the study period there was a decrease in LOS (mean 8.1 to 6.5 days, p < 0.001), grade III-V complications (13% to 7%, p < 0.05), surgical site infections (25% to 8%, p < 0.001), and anastomotic leak (11% to 3%, p < 0.05). The proportion undergoing ileostomy closure within 15 wks rose from 7% to 73% (P < 0.001). Involved CRM rates decreased from 9% to 3% (P < 0.01). TNM downstaging increased from 62% to 74% (p = 0.002). Complete response rates (clinical and pathologic) at 26wks was 26% in 2009-10 and 32% in 2014/5 (p = 0.067). Conclusions: Over the past decade, there has been a shift to MRI staging, total NT (NEO), and MIS rectal resection at 8-12 weeks. This has been associated with higher response rates, shorter LOS, and fewer complications.
Clinical outcomes of positive resection margins after endoscopic resection of early colorectal cancer.
Authors: Kim Jin-Oh 
Published: March 2017

688 Background: The management of patients with a positive resection margin after endoscopic resection of early colorectal cancer (ECC) depends on various clinical factors, including the pathology. There is little information on the clinical outcomes according to the subsequent management of a positive resection margin in patients with ECC treated by endoscopic resection. We assessed the management according to the pathology of the positive margin and evaluated the clinical outcomes. Methods: Consecutive patients with ECC who underwent endoscopic resection from January 2004 to December 2014 were reviewed. This study retrospectively analyzed 363 lesions from 338 patients (mean age, 60.1 years; 68% [230/338] male). Results: The resection margin was positive in 29.2% of patients, including cancer cells in 9.9%, adenoma in 16.5%, and high-grade dysplasia (HGD) in 2.8%. Subsequent surgery was performed on 11.8% of patients, 72.2% (26/43) of whom were cancer cell–positive, while 23.3% (10/43) were resection margin–negative but had deep submucosal (SM) or lymphatic invasion. Remnant cancer cells were identified in 25.6% (11/43) of the operated group and 81.8% (9/11) of the cancer cell–positive group. On early follow-up surveillance colonoscopy (mean interval, 3.57 months) in 88.2% of patients (320/363), including 95.7% (67/70) of the adenoma and HGD-positive group, only one (0.3%, 1/320) case of remnant adenoma was found. In the multivariate analysis, deep SM invasion ( p=0.026), number of pieces of piecemeal resection (p=0.03) and cancer cell positivity ( p=0.001) predicted subsequent surgery. In the multivariate analysis, an endoscopic appearance of incomplete resection ( p=0.002) and cancer cell positivity (p=0.041) were related to the identification of remnant cancer cells after subsequent surgery. Conclusions: Patients with an adenoma-positive resection margin had favorable clinical outcomes during subsequent surveillance. The choice of subsequent surgery was related to deep SM invasion and cancer cell–positive resection margins, and subsequent surgery group showed a high rate of remnant cancer cells.
The relationship between tumor location, tumor microenvironment, systemic inflammation, and cancer-specific survival in patients undergoing surgery for colon cancer.
Authors: Patel Meera , Park James Hugh , van Wyk Hester Catharina , Edwards Joanne , Horgan Paul G. , McMillan Donald C 
Published: March 2017

689 Background: Evidence from clinical trials and cohort studies suggest primary tumour location is a prognostic factor in patients with advanced colorectal cancer and that right and left colonic tumours should be considered as distinct clinical and biological entities. The aim of the present study was to examine the relationship between tumour location, tumour microenvironment, systemic inflammatory response (SIR), and cancer-specific survival (CSS) in patients undergoing surgery for colon cancer. Methods: Clinicopathological characteristics were extracted from a prospective database of patients who underwent potentially curative surgery for colon cancer between 1997 and 2016, at a single centre. The tumour microenvironment was assessed retrospectively using routine H&E pathological sections. Results: 722 patients were included. The majority of patients were over the age of 65 years (69%), were male (52%), had right-sided (RS) tumour location (63%), had TNM stage I/II disease (64%) and 25% received adjuvant chemotherapy. RS location was associated with poor tumour differentiation ( p =< 0.001) and high venous invasion ( p =0.003) but not with TNM stage (p= 0.310), perineural invasion ( p= 0.286), tumour budding ( p= 0.568), margin involvement ( p= 0.424), peritoneal involvement ( p= 0.689), tumour necrosis ( p= 0.423) or tumour cell proliferation ( p= 0.605). RS location was not associated with tumour inflammatory cell infiltrate at the margin (CD3+ p= 0.103, CD8+ p= 0.620) or in the tumour (CD3+ p= 0.540, CD8+ p= 0.713) or with tumour stroma percentage ( p= 0.843). RS location was associated with high mGPS ( p =0.007) and neutrophil:platelet score ( p =0.001) but not NLR ( p= 0.387). Finally, there was no difference between RS and left sided tumour location in the administration of adjuvant chemotherapy (p= 0.901) or CSS ( p= 0.951). Conclusions: Few clinicopathological features were associated with tumour location in patients undergoing surgery for colon cancer. However, RS tumour location was consistently associated with a higher SIR. This may account for the poor prognosis associated with RS tumours in patients with advanced colon cancer.
Racial and gender disparities in therapy and outcomes of squamous cell cancer of the anus.
Authors: Gupta Arjun , Arora Nivedita , Zhu Hong , Christie Alana , Meyer Jeffrey John , Khan Saad A. , Beg Muhammad S. 
Published: March 2017

691 Background: Squamous cell carcinoma of the anus (SCCA) is one of the few cancers with a rising incidence in the United States. We aimed to characterize race and gender-based disparities in receipt of therapy, and overall survival (OS) of SCCA using the Surveillance, Epidemiology and End Results (SEER) database. Methods: Cases of locoregional SCCA diagnosed between 2000-2012 in the SEER database were included. Demographics, tumor characteristics, therapy and outcomes were extracted. Primary end point was OS. Univariable and multivariable Cox proportional hazard models were constructed to test factors associated with OS. Data were reported as hazard ratios (HR) and 95% confidence intervals (CI). SAS version 9.4 was used for analysis. Results: We identified 7882 cases of locoregional SCCA, median age 58 years, 61.2% women, 86.3% white. A majority of patients (82.3%) received radiation therapy; with the lowest rate in black males (76.7%) and highest in white females (86.1%). The median OS was 135 months, and it was lower in the elderly, > 65 years (68 months), men (108 months), blacks (109 months) and those who did not receive radiation therapy (121 months). In multivariate analysis, increasing age (HR 1.19, 95 % CI 1.16-1.20 per 5 years increase), gender (HR 1.59, 95% CI 1.47- 1.73, men vs women), race (HR 1.51, 95% CI 1.34- 1.71, blacks vs whites), and receipt of radiation therapy (HR 0.90, 95% CI 0.82-0.99), were associated with OS (all p < 0.05). Race was a significant predictor of receiving radiation therapy on univariate analysis. Table 1 outlines the rates of receipt of radiation and the median OS of the four racial/gender groups. Conclusions: Significant race and gender-based disparities exist in the survival of patients with locoregional SCCA. Even after adjusting for baseline and treatment characteristics, blacks had poorer OS, suggesting difference in tumor biology. Further investigation into the causes, and methods to eliminate these disparities are warranted. [Table: see text]
Safety and effectiveness of regorafenib (REG) in patients with metastatic colorectal cancer (mCRC) in routine clinical practice: An interim analysis (IA) from the prospective, observational CORRELATE study.
Authors: Ducreux Michel , Öhler Leopold , Scheithauer Werner , Metges Jean-Philippe , Dourthe Louis-Marie , De Groot Jan Willem , Thaler Joseph , Yeh Kun-Huei , Lin Jen-Kou , Falcone Alfredo , Punt Cornelis J. A. , Contijoch Ann M. , Fiala-Buskies Sabine , Cervantes-Ruiperez Andres , O Connor Juan Manuel ,   On Behalf of the CORRELATE Investigators
Published: March 2017

700 Background: REG significantly improved overall survival (OS) vs placebo in patients with mCRC who progressed on available treatments in the randomized, double-blind, phase 3 trials CORRECT and CONCUR. CORRELATE aims to characterize the safety and effectiveness of REG for the treatment of mCRC in an unselected real-world patient population treated in routine clinical practice. Here we report the results of a planned IA. Methods: This global study aims to recruit 1000 patients with mCRC previously treated with approved therapies and for whom the decision to treat with REG has been made by the treating physician according to the local health authority approved label. Dose interruptions and reductions are permitted for the management of adverse events (AEs). The primary endpoint is the incidence of treatment-emergent AEs (TEAE; NCI-CTCAE v4.03). Secondary endpoints include OS, progression-free survival, and the disease control rate. The first planned interim analysis includes the first 500 patients observed for at least 3 months. Here, we report an IA of safety. Results: Median age was 65 years (range: 29–89) and 61% of patients were male. Most patients had a baseline ECOG PS 0/1 vs 2–4 (41%/43% vs 8%) and 50% had KRAS mutations. Most common metastatic sites at study entry were liver (52%) and lung (43%). The median treatment duration was 2.4 months (range: 0.1–10.6). The daily starting REG dose was 160 mg, 120 mg, and 80 mg in 53%, 34%, and 12% of patients, respectively; 26% of patients had dose reductions, 21% due to TEAEs. TEAEs of any grade occurred in 91% of patients, and in 76% TEAEs were considered REG related. Grade ≥ 3 TEAEs occurred in 55% of patients. In 31%, grade ≥ 3 TEAEs were REG related, with fatigue (7%), hand-foot skin reaction (5%), and hypertension (5%) being most common. Grade 5 TEAEs occurred in 13% of patients and were REG related in < 1%. Conclusions: In this observational study, the planned IA showed that the rate of REG-related grade ≥ 3 TEAEs appeared to be somewhat lower than rates observed in the phase 3 trials in patients with mCRC. The starting dose for approximately half the patients was less than 160 mg/day. Clinical trial information: NCT02042144.
Oncopre: A new chemotherapy benefit prediction algorithm to assist treatment decision making.
Authors: Yusuf Dimas , Ho Maria Yi , Kennecke Hagen F. , Cheung Winson Y. 
Published: March 2017

705 Background: Clinical decision support tools (CDSTs) can help physicians make complex treatment decisions and inform care. For colon cancer, CDSTs such as Adjuvant! Online and Numeracy were widely used to estimate the effects of adjuvant treatment and guide conversations with patients. Existing CDSTs, however, do not consider more contemporary predictive and prognostic factors, such as microsatellite instability (MSI), BRAF mutational status, or the presence of additional high risk clinical or pathological features (HRFs), in their assessment of outcomes. Current CDSTs are also not optimized for handheld devices. Methods: We developed ONCOPRE, which is an adjuvant chemotherapy benefit calculator for colon cancer that addresses the limitations of current CDSTs. Based on a comprehensive review of epidemiological data and results of landmark trials, ONCOPRE was devised to predict 5-year colon cancer recurrence and death. To validate ONCOPRE, we compared its predictions with those generated by existing CDSTs as well as real-world data from 7 tertiary cancer centers across Canada. Results: ONCOPRE is able to predict 5-year DFS and OS of patients with colon cancer based on age, sex, TNM status, and contemporary risk factors such as MSI status, BRAF mutations, and other HRFs. ONCOPRE’s predictions compare favorably with real-world data and predictions from other CDSTs. ONCOPRE’s predictions are typically more optimistic than historical outcomes, and this likely reflects the fact that current day colon cancer patients experience better prognosis with the use of modern therapy and improved supportive care. These attributes make ONCOPRE a potentially new benchmark among CDSTs that can reliably predict colon cancer outcomes. Conclusions: ONCOPRE ( http://www.oncopre.com/beta/ ) represents a new CDST that can assist in adjuvant treatment decision-making and patient counseling. We make the case that the next generation of CDSTs in oncology must take into account more contemporary clinical, biochemical, and genetic risk factors since these elements significantly affect outcomes. The ONCOPRE platform serves as a potential model on which to develop prediction tools for other forms of cancers.
Phase 1 trial of OCV-C02, a peptide vaccine for metastatic colorectal cancer patients refractory to all standard chemotherapies.
Authors: Iwasa Satoru , Taniguchi Hiroya , Yamazaki Kentaro , Yoshino Takayuki , Kiryu Chika , Liew Ei Leen , Naka Yoshiharu , Sakata Yuh 
Published: March 2017

706 Background: OCV-C02 is a peptide vaccine consisting of 2 peptide epitopes derived from ring finger protein 43 and translocase of outer mitochondrial membrane 34. In colorectal cancer (CRC), they are upregulated in approximately 80% of tumor tissues. This study was conducted to assess safety, preliminary efficacy and immunological responses to OCV-C02. Methods: Key eligibility criteria for this open label, sequential cohort, dose escalation study were patients (pts) with unresectable metastatic CRC (mCRC) refractory to all standard chemotherapies and HLA-A*24:02. Pts in cohorts 1 to 4 received OCV-C02 0.3, 1, 3 and 6 mg/body respectively, subcutaneously, on days 1, 8, 15 and 22 of the 28-day treatment cycle. Cycle was repeated in pts without progressive disease, until occurrence of unacceptable toxicity or disease progression. Primary endpoint was dose limiting toxicity (DLT) that was defined as treatment-related ≥ grade 3 or 4 hematological or ≥ grade 3 non-hematological adverse events (AEs) observed from days 1 to 29 of Cycle 1. Secondary endpoints were treatment emergent AEs (TEAEs), efficacy and immunological responses. Efficacy was evaluated by overall response rate, disease control rate (DCR), time to treatment failure (TTF) and overall survival (OS). Immunological responses were evaluated by cytotoxic T lymphocytes (CTL) and delayed-type hypersensitivity (DTH). Results: A total of 24 pts were treated. No DLT occurred in cycle 1 and no major safety issues throughout the trial. All pts had ≥ 1 TEAE. Frequently reported TEAEs included injection site reaction (25%), vomiting (25%), decreased appetite (20.8%) and pyrexia (16.7%). More than 50% of TEAEs were of grade 1 or 2 in severity. None achieved complete or partial response. Six pts had stable disease and DCR were 16.7%, 50% and 33.3% for cohorts 2, 3 and 4, respectively. TTF was 1.8, 0.9, 2.3 and 1.6 months and OS was 7.9, 11.6, 8.4 and 7.4 months for cohorts 1, 2, 3 and 4, respectively. CTL and DTH responses following vaccination were observed across the 4 cohorts. Conclusions: OCV-C02 at 0.3 to 6 mg/body exhibited a safe and well tolerated profile, and showed immunological responses in mCRC pts refractory to all standard chemotherapies. Clinical trial information: NCT01801930.