bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of second-line S-1/CPT-11+bev for advanced colon cancer (NCCSG04): Subset analysis by K-ras, EGFR, UGT1A1, and previous bevacizumab.
Authors: Takii Yasumasa , Furukawa Kouichi , Maruyama Satoshi , Yamazaki Toshiyuki , Nishimura Atsushi , Kawahara Mikako , Tomiyama Takemi , Akazawa Kohei , Hatakeyama Katsuyoshi 
Published: February 2017

564 Background: We planned a phase II trial to evaluate the efficacy and safety of irinotecan, S-1, and bevacizumab (IRIS/Bev) as second-line therapy for patients with metastatic colorectal cancer (mCRC). The result of this study was reported an active and generally well-tolerated 2nd-line treatment for mCRC (Takii et al. ASCO-GI 2013 #496). We analyzed subset of EGFR, K-ras, UGT1A1, and previous Bev. Methods: The study design was multicenter, single-arm, open-label phase II study. Eligible patients had to have mCRC with confirmed diagnosis of adenocarcinoma, history of oxaliplatin containing regimen as first-line therapy, an age from 20 to 80 years, ECOG performance status (PS) of 0-1. S-1 65 mg/m2 daily p.o. was given on days 1-14 and Irinotecan 75mg/m2and bevacizumab 10mg/kg i.v. were given on days 1 and 15 of a 28-day cycle. We retrospectively examined progression-free survival (PFS), overall response rate (OR), overall survival (OS), time to treatment failure (TTF) and safety by K-ras, EGFR, UGT1A1, and previous Bev status. Results: Thirty-four patients were investigated. The OR was 21.1% (7/33) and disease control rate was 84.8% (28/33). Median PFS was 8.9 months, median TTF was 8.2 months and median OS was 23.4 months. Median PFS was 9.9 months on K-ras wild group and 6.6 months on K-ras mutant group (p = 0.517). Median OS was not reached on K-ras wild group and 16.4 months on K-ras mutant group (p = 0.097). The EGFR-negative case was three cases, and it did not become a data to compare because of small number. Median PFS was 8.5 months on previous Bev group and 9.9 months on previous no-Bev group (p = 0.637). Median OS was not reached on previous Bev group and 23.1 months on previous no-Bev group (p = 0.701). Median PFS, TTF and OS was no different between UGT1A1 wild group and mutant group. On safety analysis, there were no different between the two groups, respectively. Conclusions: IRIS/Bev is an active and well-tolerated second-line treatment for patients with mCRC. Only K-ras status influendced OS. Clinical trial information: UMIN000001631.
Peritoneal surface disease (PSD) from appendiceal cancer treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): Overview of 481 cases.
Authors: Votanopoulos Konstantinos I. , Russell Greg B. , Randle Reese W. , Shen Perry , Stewart John H. , Levine Edward Allen 
Published: February 2017

565 Background: Appendiceal cancer PSD treated with CRS/HIPEC has shown significant variability in the obtained survival benefit. Methods: A prospective database of 1,069 procedures was reviewed for primary, grade, nodal and performance status, resection type, morbidity, mortality, and survival. Results: 481 CRS/HIPEC procedures, 317 (77.3%) for low grade (LGA) and 93 (22.7%) for high grade (HGA) appendiceal primaries, were identified. Median follow up was 44.4 months. 30 and 90 day major morbidity were 27.8% and 9.3% while the 30 and 90 day mortality was 2.7% and 5.6% respectively. Median ICU and hospital stay was 1 and 9 days. In multivariate analysis, Clavien III/IV complications, were related to incomplete CRS (p = 0.0037), involved nodes (p < 0.0001) and comorbidities (p = 0.003). Multivariate analysis of the LGA patients indicated survival to be dependent on nodal status (p = 0.003 HR 3.6), complete cytoreduction (p < 0.0001) and preoperative chemotherapy (p = 0.04 HR 2.2). The multivariate survival of HGA was dependent on complete cytoreduction (p = 0.0003 HR 3.8) and preoperative chemotherapy (p = 0.0064 HR 2.5). In patients with complete cytoreduction, median survival for node positive LGA and HGA patients was less than their node negative counterparts. (85 months vs. not reached (82% alive at 90 months) and 30 vs. 153 months respectively p < 0.0001). Conclusions: Positive nodes are associated with decreased survival not only in HGA but also in LGA patients even after a complete cytoreduction. Nodal status is superior to grade of disease as a prognostic indicator of survival. Node negative HGA primaries after complete CRS can obtain a comparable survival benefit to LGA counterparts.
Causes of urban-rural disparities in adjuvant chemotherapy (AC) for rectal cancer (RC).
Authors: Rasool Javaheri Khodadad , Speers Caroline , Cheung Winson Y. 
Published: February 2017

568 Background: While urban-rural differences in cancer care are well described, the etiology for such disparities is unclear. Our aim was to determine whether differences in AC use are mediated through variations in community size (CS) and whether differences in AC use translated into differences in patient survival outcomes (SO). Methods: Patients with stage II/III RC from 1999 to 2009 and referred to any 1 of 5 regional cancer centers in British Columbia were reviewed. Communities were classified as rural (R), small urban (SU), moderate urban (MU), and large urban (LU) based on census data. Using zip codes and a distance matrix application interface, driving distance (DD) to patients’ respective cancer center (CC) was determined and categorized into quartiles. Stepwise logistic regression was used to explore AC use based on urban-rural communities, controlling for DD. Cox regression was used to identify whether variations in CS translated into differences in SO. Results: A total of 2618 patients were identified: median age 67 years (IQR 58-75), 64% men, and 63% received AC. Patients were distributed across various communities: R 37%; SU 11%; MU 13%; and LU 39%. There were no differences in baseline characteristics based on CS (all p<0.05). Compared to patients in LU centers, those living in R, SU and MU areas were less likely to be treated with AC (55 % vs. 49% vs. 71%, respectively, p<0.001). Likewise, DD was shortest for LU and longest for R residents (p<0.001). In multivariate analysis that controlled for confounders, urban-rural disparities in receipt of AC persisted, and these differences were significantly increased after adjusting for DD (Table). In Cox regression analysis which controlled for confounders, patients who lived in R, SU, and MU regions did not have a significantly inferior SO in comparison to those living in LU areas (HR: 0.926, 0.813, 1.006, respectively, p=0.47). Conclusions: There are urban-rural disparities in access to AC independent of patients’ DD to CC. These disparities do not seem to alter patients’ SO. [Table: see text]
Do inflammatory bowel disease patients experience more toxicity after radiotherapy for colorectal and anal cancer?
Authors: Chang Bianca W. , Kumar Aryavarta M. S. , Kiran Ravi P. , Kalady Matthew F. , Lavery Ian C. , Abdel-Wahab May 
Published: February 2017

570 Background: Despite potential oncologic gains from using radiotherapy in patients with inflammatory bowel disease (IBD), it has historically been contraindicated due to increased acute gastrointestinal (GI) toxicity. Yet recent published literature is mixed with regards to toxicity outcomes in these patients. In this study, we examine GI, genitourinary (GU), and skin toxicity in IBD patients compared to non-IBD patients both treated with external beam radiation therapy (EBRT) for anal or colorectal cancer (CRC). Methods: Anal and CRC patients who received EBRT were included in this single institutional IRB-approved study. 15 IBD patients and 30 non-IBD patients were matched 1:2 based on age (±5 years), treatment year (±1 year), BMI (±10 kg/m2), and clinical stage. No IBD patients had documented active disease at the time of treatment. All patients had a pathologic diagnosis of anal or CRC and received EBRT either neoadjuvantly or adjuvantly. Acute toxicity occurred within 100 days of EBRT. Data was collected via retrospective review of the treatment charts. Results: All patients received radiation doses between 45-52 Gy in 1.8Gy/fx or 2Gy/fx, delivered using AP/PA, IMRT, 3-field, or 4-field plans. There was no difference in the rate of grade 3 (20% vs 7%, p=0.19) or grade 4 (7% vs 0%, p=0.13) lower GI toxicity. There was also no difference in the incidence of GU (47% vs 30%, p=0.37), upper GI (60% vs 33.3%, p=0.08), or skin toxicity (40% vs 64%, p=0.17). Post-operatively, IBD patients had a significantly higher rate of wound dehiscence (35.7% vs 7.1%, p=0.02); however, there was no difference in the rate of bleeding (29% vs 18%, p=0.43), infection (50% vs 32%, p=0.50), or ileus (36% vs 11%, p=0.06). Conclusions: IBD patients with anal or CRC who received EBRT neoadjuvantly or adjuvantly did not experience more acute GI, GU, or skin toxicity than matched non-IBD patients with similar treatment. Post-operatively, IBD patients were more likely to have wound dehiscence, but were not more likely to have bleeding, infection, or ileus.
Final results of phase II study of S-1, oral leucovorin, oxaliplatin, and bevacizumab combination therapy (SOL+BV; SOLA) in metastatic colorectal cancer (mCRC).
Authors: Yamazaki Kentaro , Nishina Tomohiro , Kato Takeshi , Yoshino Takayuki , Miyata Yoshinori , Esaki Taito , Moriwaki Toshikazu , Boku Narikazu , Hyodo Ichinosuke 
Published: February 2017

574 Background: The SOL regimen (S-1, Oral Leucovorin; LV, and Oxaliplatin) demonstrated a promising activity with tolerated toxicities compared to mFOLFOX6 in a randomized phase II study for mCRC. We previously reported the promising results of a phase II study of SOL+BV in Gastrointestinal Cancers Symposium 2012 (Kato T, et al.) focusing on early clinical outcomes, overall response rate (ORR), progression free survival (PFS) and safety. The final follow-up (cut-off date Dec 2012) has been completed, and we report up-dated overall survival (OS) and the impact of early objective tumor response (EOTR) on OS in the present report. Methods: The main inclusion criteria were; (1) metastatic colorectal adenocarcinoma, (2) age ≥20 years, (3) no prior chemotherapy, (4) target lesion (RECIST v1.0), (5) ECOG PS 0-1, 6) written informed consent. Patients (pts) received S-1 (40-60 mg bid) and LV (25 mg bid) orally for one week. Oxaliplatin (85 mg/m2) and BV (5 mg/kg) were administered on day 1. This treatment was repeated every 2 weeks. The primary endpoint was ORR confirmed by the independent review committee according to RECIST v1.0. This trial was supported by Taiho Pharmaceutical CO, LTD. (JAPIC Clinical Trials information Identifier: JapicCTI-090881). Results: From Oct 2009 to Apr 2010, 31 pts were enrolled. Of the eligible 29 pts, median age was 62; PS 0/1 was 24/5; number of metastatic organs 1/≥2 was 15/14. ORR was 86% (95%CI, 68-96), and the median PFS was 15 months (95%CI, 10-26). OS has not reached median with a median follow-up time of 34 months. Two-year survival rate was 72%. EOTR (RECIST sum ≥30% shrinkage) at 6-weeks was observed in 35% of pts. Two-year survival rate in these pts with an EOTR at 6-weeks was 80%, while in other pts without an EOTR at 6-weeks was 68%. The curative resection rate of metastatic lesions was 28%. The incidence (≥10%) of grade 3/4 adverse drug reactions were; neutropenia 20%, hypertension 23%, anorexia 20%, fatigue 17%, diarrhea 10%, and sensory neuropathy 53%. Conclusions: The SOL+BV regimen showed the promising activity for mCRC. The high proportion of EOTR might lead to long survival. Further evaluation of this regimen would be warranted. Clinical trial information: 090881.
Volumetric analysis of anal cancer relapses following radical chemoradiation.
Authors: Muirhead Rebecca , Durrant Lisa , Hyde Katherine , Hawkins Maria 
Published: February 2017

576 Background: Definitive chemoradiotherapy is standard of care in anal squamous cell carcinoma. The ACT II trial set the standard achieving three year overall survival rates of 73%. However patients with locally advanced disease have a ~50% local relapse rate. Studies have failed to demonstrate an improvement in local relapse rate by altering the systemic therapy. Although 2/3 of relapses are local as opposed to regional or distant, there is limited knowledge on the 3D position of these relapses. We aim to retrospectively review the patterns of local failure in three dimensions, relative to the radiotherapy plan. Methods: Between February 2007 and April 2012, 77 patients were treated for squamous cell carcinoma of the anus with radical chemoradiotherapy. Early stage (T0/2) and locally advanced (T3/4) tumours constituted 53% and 44% respectively. 37% of patients had nodal disease. As per ACT II protocol we used a gross tumour volume (GTV) to PTV margin of 3cm and prescribed to a dose of 50.4Gy. In patients with a local recurrence, imaging from the time of recurrence was imported into the radiotherapy planning system. The volume and site of gross recurrence was noted relative to the previous GTV and 95% isodose line. The mean dose delivered to the relapsed area was calculated. Results: Median follow-up was 42 months (range 14 to 78 months). Eight (10%) patients failed to respond. Six (8%) patients developed an isolated local relapse, 2 (3%) distant metastatic disease alone and 1 both local and distant relapse. Of those that relapsed locally, 5 patients were T2N0, one T3N0 and 1 node positive. There were no regional relapses. The entire macroscopic relapse lay within the 95% isodose line of the 50.4Gy in all patients. The median percentage of relapse that lay within GTV was 63% (range 29 to 100%). A GTV to PTV margin of 2cm would have encompassed all macroscopic relapses. The median doses to relapsed area was 52Gy (range 51Gy to 53Gy) with the minimum dose to any relapsed area being 49Gy. Conclusions: The majority of relapses centred on the GTV suggesting the gross tumour was uncontrolled with current doses in these patients. A reduction of GTV to PTV margin may be appropriate, facilitating trials of dose escalation with the aim of improving outcomes.
Preliminary results of preoperative FOLFOX chemotherapy for locally advanced colon cancer patients with therapeutic drug monitoring of 5-FU.
Authors: Rodriguez Javier , Martin Romano Patricia , Aldaz Azucena , Chopitea Ana , Baixauli Jorge , Subtil Jose Carlos , Zufia Laura , Garzon Carlos , Sola Iosu , Castanon Eduardo , Hernandez-Lizoain Jose Luis 
Published: February 2017

579 Background: Preoperative chemotherapy is an alternative approach undergoing active clinical research in patients (pts) with locally advanced colon cancer (LACC). The aim of this study was to assess the feasibility and preliminary evidence of activity of a direct monitoring of 5-FU levels based on pharmacokinetically (PK) guided dose adjustments. Methods: LACC pts (T4 or T3 with extramural depth >5mm) diagnosed after a colonoscopy and spiral CT were scheduled to receive 4 cycles of Oxalipatin (85mg/m²), Leucovorin (400 mg/m²), bolus 5-FU (400 mg/m2) and infusional 5-FU (initial dose of 2400mg/m² in 46h and then tailored according to PK monitoring to reach an area under the curve (AUC) between 25-30 mg·h·L-1). Surgery was planned 4 to 6 weeks after the completion of chemotherapy treatment. All pts were staged at baseline and before surgery. Pathological tumor regression was graded according to the MSKCC classification. Toxicity was reported according to the NCI-CTCAE 4.0. Results: From March 2011 to April 2013, 16 pts (M/F: 10/6; median age 56) with LACC were evaluated. Median dose of 5-FU was 4750 mg. 70.6% pts required a 5-FU dose increase to reach the target AUC. Median 5-Fu plasma clearance was 199,58 L/h. Side effect profile included G3 neutropenia (6 pts), G2 diarrhea (5 pts), G2 nausea (3 pts) and G2 asthenia (4 pts). Neoadjuvant treatment was discontinued in 2 pts due to small bowell obstruction requiring surgery. No progressive disease was observed during preoperative chemotherapy. A radiological dowstaging was achieved in 9 pts (56.25%). All pts underwent surgery (laparoscopy-assisted 50%) with an R0 resection rate of 93.75%. There were no treatment-related deaths. Pathological responses (MSKCC score) included grades 4, 3+ and 3 in 12.5%, 12.5% and 25% of pts, respectively. Median number of harvested nodes was 23.5 (7-51) with a ypN0 rate of 75%. Median time to hospital discharge was 7 days. After a median follow-up of 7 months (3-27), the 2-year actuarial median PFS and OS were 67.5% and 100%. Conclusions: Preoperative PK-adjusted FOLFOX in LACC pts achieves major pathological responses in almost 50% the pts and a remarkable R0 resection rate. Further research seems warranted.
Predictors of treatment interruption/dose reduction of neoadjuvant chemotherapy for rectal cancer: A multicenter study.
Authors: Raissouni Soundouss , Armstrong Dawn Elizabeth , Price Hiller Julie A. , Mercer Jamison , Powell Erin Diana , MacLean Anthony , Jiang Maria , Doll Corinne M. , Goodwin Rachel Anne , Batuyong Eugene , Zhou Kevin , Monzon Jose Gerard , Tang Patricia , Heng Daniel Yick Chin , Cheung Winson Y. , Vickers Michael M. 
Published: February 2017

580 Background: Neoadjuvant chemoradiation (CRT) is the standard of care for patients with locally advanced rectal cancer. Many patients require dose reduction or chemotherapy interruption due to significant toxicities. To assess the predictors of neoadjuvant chemotherapy treatment (tx) adjustments, we performed a retrospective study in four Canadian provinces. Methods: Cancer Registries identified consecutive patients with clinical stage I-III rectal cancer from the Tom Baker Cancer Center, Cross Cancer Institute, BC Cancer Agency, Ottawa Hospital Cancer Centre and the Dr. H. Bliss Murphy Cancer Centre who received CRT and had curative intent surgery (Sx) from 2005 to 2012. Patient, tumor and tx characteristics were correlated with treatment completion. Results: Of the 891 patients included, 886 patients had tx dose adjustments data available. 738 (83.2%) completed the planned neoadjuvant chemotherapy, while 148 (16.7%) failed to complete planned chemotherapy. Patients who required tx interruption/cessation or dose reduction were more likely to be female, elderly, had higher ECOG PS and were treated with fluorouracil (FU) chemotherapy in univariate analysis (see Table). On multivariable analysis, female gender (OR 1.807, 95% CI 1.02-3.2, p=0.042) and tx with FU (vs capecitabine) (OR 2.7, 95% CI 1.52-4.77, p=0.0007) were associated with dose reduction and tx interruption/cessation. Conclusions: Gender and type of chemotherapy are predictors of neoadjuvant chemotherapy interruption or dose reduction in rectal cancer. Careful monitoring of these patients is warranted during neoadjuvant CRT. [Table: see text]
Does first-line treatment impact the cost-effectiveness of second-line treatment for elderly metastatic colon cancer patients?
Authors: Mullins C. Daniel , Woldemichael Andinet , Zheng Zhiyuan , Onukwugha Ebere , Seal Brian S. , Hanna Nader 
Published: February 2017

585 Background: Randomized clinical trials for second line treatment (Tx2) of metastatic colon cancer (mCC) often have strict inclusion/exclusion criteria regarding prior treatment, yet in the real world there is significant variation. This study aims to determine whether cost effectiveness estimates of Tx2 for elderly mCC patients varies by the regimen they received in first-line treatment (Tx1). Methods: We identified 3,211 elderly (age 66+) mCC patients in the SEER-Medicare dataset who received NCCN recommended Tx1 between 2003 and 2009. Patients were categorized by Tx1 based on a previously published algorithm as fluorouracil and leucovorin (5-FU/LV), irinotecan (IRI), oxaliplatin (OX), or “other,” which included IROX or biologics without OX or IRI. Separate 5-year incremental cost-effectiveness of Tx2 were calculated for each Tx1. Approximately 1% of patients with outlier costs were excluded. Patients enrolled in HMOs, lost Part A and/or B, and died of causes other than colon cancer are censored. We adjusted for censoring using the Inverse Probability Weighting (IPW) method. Costs were inflation-adjusted to 2009 dollars using the national monthly medical price index. Results: Among patients who received Tx1, 34% (n=1,090) received 5FU, 17% (n=530) received IRI, 46% (n=1,481) received OX, and 3% (n=110) received other (IROX or Biologics) regimens; 44.5% (n=1,440) proceeded to Tx2. Compared to those who do not receive Tx2, patients who received Tx2 following IROX or Biologics, IRI and 5FU in Tx1 live 292 (se = 4), 224 (se = 2), and 191 (se = 2) days longer and incur added costs of $49,096 (se = $7,137), $83,784 (se = $12,322), and $91,686 (se = $10,312), respectively. Recipients of OX in Tx1 did not receive a survival benefit from Tx2, despite additional costs of $46,849 (se = $10,468). Conclusions: The real-world survival benefit of Tx2 for elderly mCC patients in SEER-Medicare varied based on Tx1 from potential harm to a mean of 292 days of incremental survival. Similarly, the costs and cost effectiveness of Tx2 varied by Tx1. These results underscore the importance of considering prior treatment when evaluating the benefit of subsequent treatment for elderly mCC patients.
Analysis of KRAS/NRAS, PI3CA, and BRAF mutations in the phase II KSCC0901 study of cetuximab plus S-1 as third-line treatment for metastatic colorectal cancer in Japanese patients.
Authors: Emi Yasunori , Oki Eiji , Saeki Hiroshi , Kitao Hiroyuki , Samura Hironori , Takahashi Takao , Sawai Terumitsu , Akagi Yoshito , Tsuji Akihito , Eguchi Susumu , Yoshida Kazuhiro , Baba Hideo , Ogata Yutaka , Natsugoe Shoji , Shimokawa Mototugu , Maehara Yoshihiko ,   Kyushu Study Group of Clinical Cancer (KSCC)
Published: February 2017

587 Background: Exploratory biomarker studies in the randomized phase III PRIME study suggested that patients with mCRC tumors harboring a mutation (MT) in KRAS or NRAS (beyond KRAS exon 2) do not respond to panitumumab-FOLFOX4 (2013 ASCO, JCO 31, #3511). We reported the efficacy and safety of S-1+. Cetuximab (Cmab) in wild-type (WT)-KRAS (exon 2) mCRC patients (pts) as third-line therapy (KSCC0901) (2012 ASCO, JCO 30, s3558). The full spectrum of characterized RAS (KRAS and NRAS), PI3CA, and BRAFMTs may affect efficacy in S-1+Cmab therapy in Japanese patients. Methods: An analysis was conducted to assess the treatment effect of S-1+Cmab, according to RAS (KRAS and NRAS), PI3CA, and BRAF MTs. The treatment protocol of KSCC0901 was as follows: weekly intravenous Cmab administration of 400 mg/m2 (day 1), 250 mg/m2/week (following day 1) and oral administration of 80 mg/m2/day S-1 on days 1–28 of each 42-day cycle. MTs in KRAS codons 12 and 13 (exon 2) were detected using direct sequencing according to the manufacturer’s instructions. MTs in KRAS codons 61 and 146, NRAS codons 12, 13 and 61, BRAF codon 600 and PIK3CA codons 542, 545, 546, and 1047 were detected using the multiplex PCR-Luminex method-based MEBGEN MT Kit (Medical and Biological Laboratories, Nagoya, Japan). Results: 35 pts were eligible for the analysis. Number of MT cases of KRAS, NRAS, BRAF, and PIK3CA were 4, 2, 2, and 5, respectively. One case had MTs of NRAS and PIK3CA. In 37 cases with WT KRASexon2 pts, median progression-free survival (mPFS) was 5.6 [95% CI: 4.4 – 5.7] months; median overall survival (mOS), 13.5 [8.5-16.5] months; and best overall response (ORR), 37.8%. In the all-WT subgroup 23 cases, mPFS was 5.6 [5.1-7.1] months; mOS, 13.5 [9.3-21.2] months; and best ORR, 47.8%. In 12 patients with any MT, mPFS was 4.0 [2.7-7.5] months; mOS, 5.5[2.9- ] months; and best ORR, 16.7%. Conclusions: These results suggest that also in Japanese patients receiving a Cmab containing regimen, RAS, BRAF and PIK3CA MT status beyond KRAS exon2 might predict non-responders to treatment. Clinical trial information: UMIN000002475.