bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of S-1 plus oxaliplatin combined with radiation (SOX/RT) for preoperative locally advanced rectal carcinoma (JACCRO CC-04: SHOGUN trial).
Authors: Watanabe Toshiaki , Matsusaka Satoshi , Ishihara Soichiro , Kondo Keisaku , Horie Hisanaga , Uehara Keisuke , Oguchi Masahiko , Murofushi Keiko , Ueno Masashi , Mizunuma Nobuyuki , Kato Daiki , Hashiguchi Yojiro , Shimbo Taiju , Okuda Junji , Nakazawa Masanori , Sunami Eiji , Kawai Kazushige , Yamashita Hideomi , Okada Tohru , Ishikawa Yuichi 
Published: February 2017

602 Background: Previous western trials of preoperative chemoradiation (CRT) in patients with locally advanced rectal carcinoma (LARC) have been shown to increase the chance of sphincter preservation and local control, and has become the standard of care in western countries. In Japan, preoperative CRT has not been utilized in LARC and its value is unconfirmed. Thus, we conducted a phase I/II study of preoperative CRT with S-1, which is widely used oral fluoropyrimidine in Japan to treat gastrointestinal cancer, plus oxaliplatin in patients with LARC. Methods: Patients with histopathologically confirmed LARC (cT3-T4, any N) were eligible. A total radiation dose of 50.4 Gy was delivered in 28 fractions over 5 weeks, and S-1 was orally administered 40mg/m2 twice a day for 5 days a week at 1st, 2nd, 4th and 5th week. Oxaliplatin was administered at a dose of 40 mg/m2 (level 1), 50 mg/m2 (level 2) or 60 mg/m2(level 3) on day 1, 8, 22 and 29. Surgery was performed within 6-10 weeks after CRT. The primary endpoint of phase I part was to determine the maximum tolerated dose (MTD) and the recommended dose (RD) of oxaliplatin. Primary endpoint of phase II was evaluated pathologic complete response (pCR) rate at RD. Results: 13 patients were enrolled in the phase I part, 2 dose-limiting toxicities (DLTs, skipping oxaliplatin due to the grade 2 neutropenia) occurred in the dose level 3, and the MTD was not reached. In phase II, 45 patients were treated at the RD of oxaliplatin (60 mg/m2) and 44 patients (97.8%) underwent surgery. A pCR was observed in 12 patients (27.3%). The relative dose intensity of radiation, S-1, oxaliplatin was 98.4%, 94.0%, and 94.3%, respectively. The incidence of grade 3-4 diarrhea and neutropenia was 8.9% and 2.2%, respectively. Postoperative complications of any grade occurred in 27.3% of patients. Conclusions: Preoperative CRT with S-1 plus oxaliplatin showed promising results in pathological responses and favorable toxicities profiles. Clinical trial information: NCT01227239.
The efficacy of first-line IRIS with or without bevacizumab in patients with metastatic colorectal cancer: Including multivariate analysis of two phase II studies.
Authors: Yuki Satoshi , Komatsu Yoshito , Fukushima Hiraku , Sasaki Takahide , Kobayashi Yoshimitsu , Harada Kazuaki , Amano Toraji , Nakamura Michio , Kudo Mineo , Tateyama Miki , Hatanaka Kazuteru , Saitoh Soh , Miyagishima Takuto , Kato Takashi , Kawamoto Yasuyuki , Takagi Tomofumi , Iwanaga Ichiro , Miyashita Kencho , Onodera Manabu , Sakata Yuh 
Published: February 2017

603 Background: The safety and efficacy of first-line IRIS (S-1 in combination with irinotecan) and IRIS/Bev (IRIS in combination with bevacizumab [Bev]) have been evaluated in patients with metastatic colorectal cancer (mCRC). To date, no randomized studies comparing these regimens have been performed. This retrospective analysis compared efficacy data for the two regimens from separate phase II studies performed at Hokkaido Gastrointestinal Cancer Study Group (HGCSG). Methods: Patients with histologically confirmed unresectable metastatic or recurrent CRC and received no prior chemotherapy were enrolled. In the first trial, patients received irinotecan 100 mg/m2 on day 1,15 and oral S-1 40 mg/m2 twice daily on days 1-14 every 4 weeks (IRIS study: HGCSG0302). In the second trial, patients received the same regimen plus Bev 5 mg/kg on day 1,15 (IRIS/Bev study). Results: A total of 40 and 52 patients were enrolled the IRIS and IRIS/Bev studies, respectively. Patient characteristics were generally similar in both groups, whereas there were more cases of good performance status and less number of metastatic organ in IRIS/Bev group. The median overall survival was 39.6 months in IRIS/Bev, as compared with 23.4 months in IRIS, corresponding to a hazard ratio for death of 0.418 (p<0.001). The median progression-free survival was 17.0 months in IRIS/Bev, as compared with 8.6 months in IRIS (hazard ratio for disease progression, 0.402; p < 0.001); the corresponding response rate were 63.5 percent and 52.5 percent (p = 0.393). In a multivariate analysis of PFS and OS, IRIS/Bev was significantly associated with longer PFS and OS compared with IRIS alone. Conclusions: In this retrospective comparison of two studies, the addition of Bev to IRIS appeared to improve outcome compared with IRIS alone in the first-line treatment of patients with mCRC.
Association of bevacizumab-free interval with efficacy of anti-EGFR therapy in patients with metastatic colorectal cancer.
Authors: Komori Azusa , Taniguchi Hiroya , Narita Yukiya , Uegaki Shiori , Nitta Sohhei , Yamaguchi Kazuhisa , Nomura Motoo , Kadowaki Shigenori , Takahari Daisuke , Ura Takashi , Andoh Masashi , Muro Kei 
Published: February 2017

610 Background: Both bevacizumab (Bev) and anti-EGFR agents are sequentially used for metastatic colorectal cancer (mCRC). Some basic studies reported the interaction between Bev and anti-EGFR agents in vivo. Therefore we hypothesized the shorter Bev-free interval may lead to poor outcome of anti-EGFR therapy. The aim of this study is to examine the association of the interval between last Bev administration and initial anti-EGFR agents with efficacy of anti-EGFR therapy. Methods: We retrospectively reviewed consecutive mCRC patients who underwent combination therapy of anti-EGFR agents and irinotecan after failure of fluoropyrimidines, oxaliplatin, irinotecan, and Bev at a single institution. We divided patients in two groups (group A: the interval between Bev and anti-EGFR agents <6M, group B: ≥6M). Results: A total of 114 patients constituted the cohort of analysis. The median age was 63; 78 (68%) patients were male. Most patients (N=100, 88%) were treated with cetuximab, and 14 patients were panitumumab. Seventy-four patients were group A and 40 patients group B, respectively. There was no significant difference in patient characteristics. Response rate was 24.7% in group A, and 50.0% in group B (p=0.0072). The patients in group B have significantly longer progression free survival (4.2 vs. 6.6 M, HR 0.65, 95% CI 0.43- 0.98, p=0.042) and longer overall survival (11.6 vs. 14.3 M, HR 0.62, 95% CI 0.39- 0.97, p=0.038). Conclusions: The short interval (<6M) between last Bev and anti-EGFR agents may interfere with the efficacy of anti-EGFR therapy.
A dose-escalation study of oxaliplatin/capecitabine/irinotecan (XELOXIRI) and bevacizumab (bev) as a first-line therapy for patients with metastatic colorectal cancer.
Authors: Sato Yasushi , Ohnuma Hiroyuki , Hirakawa Masahiro , Takahashi Minoru , Osuga Takahiro , Takada Kohichi , Hayashi Tsuyoshi , Sato Tsutomu , Miyanishi Koji , Takimoto Rishu , Kobune Masayoshi , Okita Kenji , Furuhata Tomohisa , Hirata Koichi , Kato Junji 
Published: February 2017

612 Background: In a recent study by Loupakis, F. et al. (ASCO-GI 2013), a FOLFOXIRI and bevacizumab regimen showed promising activity and conversion rate in patients (pts) with metastatic colorectal cancer (mCRC). In order to evaluate a treatment regimen that was easier to administer, we conducted a dose-escalation study to determine the recommended dose (RD) of irinotecan (IRI) in combination with oxaliplatin and capecitabine and bevacizumab (XELOXIRI/bev) in pts with mCRC. Methods: Pts were eligible if they had mCRC (liver and/or other metastases), ECOG PS 0-1, were either negative or heterozygous for UGT1A1*6 or UGT1A1*28 and were not pretreated for metastatic disease. Treatment consisted of oxaliplatin (100 mg/m2 day 1), capecitabine (1700 mg/m2/day from day 2 to 15), IRI (100,120,150 mg/m2 for dose levels 1, 2, or 3, day 1) and bev (7.5 mg/kg, day 1), repeated every 3 weeks. The dose of IRI was escalated if dose limiting toxicities (DLT) were absent in the first three pts per cohort, or if <2 DLTs were observed in six pts. If the MTD was not reached at the planned dose levels, the RD of IRI was defined as 150mg/m2, which is the maximum dosage approved for use in Japan. Results: 12 pts (F/M: 4/8, median age: 58 years, PS 0/1: 11/1) received a median of 6 cycles of therapy (range 2-12). The DLT was grade 4 neutropenia, which was observed in 1 of 6 pts at dose level 2. MTD was not reached at dose level 3. Therefore, the RD of IRI was defined as 150 mg/m2. Most common grade ≥ 3 toxicities were neutropenia (58.3%), anemia (16.6 %), diarrhea (8.3%), and febrile neutropenia (8.3 %). The response rate was 83.3%(95% CI 60-89), including 1 CR, 9 PRs. The disease control rate was 100%(95% CI 80-100). At a median follow-up of 8 months, median PFS was 15 months and median OS was not yet reached. Conclusions: XELOXIRI/bev is a feasible regimen; neutropenia was the DLT; recommended dose of IRI is 150 mg/m². The observed response rate of 83.3% is very promising and warrants further investigation. Clinical trial information: UMIN000005440.
Does interval from histologic diagnosis (Dx) to start of chemotherapy (Ctx) impact survival in metastatic colorectal cancer (MCRC)?
Authors: Jayaram Anuradha , Teo MinYuen , Keegan Niamh , Harrold Emily , Coleman Niamh , Kennedy M. John 
Published: February 2017

615 Background: Optimal timing from colorectal surgery to initiation of adjuvant chemotherapy is between 4 to 6 weeks based on recent data. In MCRC, therapeutic benefits of ctx are frequently calculated from start of treatment. We investigated whether the interval between dx and commencement of ctx influences overall survival (OS) in patients (pts) with MCRC. Methods: Pts with CRC were identified from the institutional database. Inclusion criteria were MCRC and receipt of ctx. Clinicopathologic details were collected. Intervals from histologic dx to ctx were calculated. Analyses were based on receipt of ctx within 4 weeks (w), 5-8w and > 8w of dx. Survival was compared between groups. OS was presented as hazard ratio (HR) with associated p value. Results: Between 2003 and 2013, 123 pts were identified, where 58 pts receive ctx within 4w, 38 within 5-8w and 27 > 8w. Median OS (mOS) was 8.7, 15.7 and 13.7 months (mths) respectively. Improvement in OS was noted in pts treated 5-8w and >8w compared to within 4w (HR 0.53, 0.45; p=<0.01, <0.01). Surgical resection of the primary was noted in 14% of pts receiving ctx in 4w, 45% between 5-8w and 70% > 8w and mOS amongst these groups were 19.5, 16.3, and 22.1 mths respectively versus 6.5, 10.5 and 8.9 mths in similar groups without surgery. Improved OS in resected pts is noted in when treated 5-8w and > 8w compared to 4w (HR 0.76, 0.72 p= 0.55, 0.46) with no difference in OS between groups treated at 5-8w and > 8 w (HR 1.06, p= 0.85). Univariate and multivariate analyses for 5 variables are described in the Table, two of which are statistically significant on multivariate analyses. Conclusions: Our data did not suggest a detrimental effect on OS from ctx delay and the lack of survival benefit from early ctx might be due to a number of confounding variables as described above. [Table: see text]
Neoadjuvant chemoradiotherapy for locally advanced rectal cancer: Predicting long-term outcomes based on response to treatment.
Authors: Laws Kirsten Elizabeth Jean , Wilson Christina , McIntosh David , Harrow Stephen 
Published: February 2017

621 Background: Neoadjuvant long course chemoradiotherapy is well recognised as a standard treatment in locally advanced, margin threatening rectal cancer, in order to downstage and reduce local recurrence. We investigated retrospectively whether long term outcomes could be predicted by response to neoadjuvant treatment, and which factors specifically seemed to predict a risk of poorer outcome. Methods: All patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified retrospectively. Patients were excluded if the treatment indication was for inoperable disease, postoperative, recurrence, or palliative intent. A total of 231 patients were analysed with retrospective analysis of all electronic records and case notes. The following information was collated: preoperative staging, chemoradiotherapy treatment planned and received, operation performed, postoperative pathology (including nodal status, margins, presence of LVSI, and evidence of response to neoadjuvant treatment), disease free survival, and overall survival. Results: Kaplan Meier curves are presented showing patients with either a complete or partial response to neoadjuvant treatment appear to have a statistically significant improvement in long term outcomes, compared to those with no response (Mean survival 55 months, 56 months and 43months respectively, p<0.01). Furthermore, those who remain node positive or have evidence of LVSI following neoadjuvant treatment appear to have a statistically significant poorer outcome. Conclusions: Our study further develops on previous work looking at the prediction of outcomes following response to neoadjuvant treatment in rectal cancer. It appears that those who respond to initial treatment will have a better outcome than those who do not, including those who remain node positive or with LVSI following treatment. This study is limited because it is retrospective. Randomised controlled trial data is required to enable identification of poor risk imaging and pathology features that might suggest the need for adjuvant therapy following combined modality treatment with neoadjuvant chemoradiotherapy and surgery.
The safety of chemotherapy for colorectal cancer patients with hepatitis C virus infection.
Authors: Tomizawa Kenji , Suyama Koichi , Miura Yuji , Shimomura Akihiko , Hanaoka Yutaka , Toda Shigeo , Moriyama Jin , Matoba Shuichiro , Takano Toshimi , Kuroyanagi Hiroya 
Published: February 2017

629 Background: Hepatitis C virus (HCV) infection is one of the most common blood-borne infection in the world, and with an estimated to be infected more than 880,000 people in Japan. Little is known about the changes of HCV status during chemotherapy and the influence of HCV infection on toxicity of chemotherapy. Methods: We reviewed all patients diagnosed with colorectal cancer in our institution between 2001 and 2012 who had been screened for HCV infection by testing for anti-HCV antibody and identified 77 HCV-infected patients. We retrospectively analyzed the change in HCV load and the toxicities of chemotherapy in these patients. Results: Twenty-four of the 77 HCV-infected patients with colorectal cancer had received chemotherapy.The median age was 66 years (range: 42-80 years). Four patients had liver cirrhosis at the initiation of chemotherapy. The remaining 20 patients were diagnosed with chronic hepatitis, and their liver function tests and complete blood cell counts at baseline were normal. First-line chemotherapy included 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) (n = 6), S-1 and irinotecan (IRIS) (n = 1), tegafur-uracil (n = 14), capecitabine (n = 1), capecitabine and oxaliplatin (XELOX) (n = 2).Serum HCV-RNA levels both before and after chemotherapy were evaluated in 10 patients, and the median serum HCV-RNA level before and after chemotherapy was 4.0 and 3.05 logIU/ml, respectively. Transaminase levels were elevated during chemotherapy in 2 patients. There were no patients suffered from grade 3-4 neutropenia or febrile neutropenia. Conclusions: This study indicates that chemotherapy can be safely performed in HCV-infected patients with colorectal cancer without change in HCV load.
Reintroduction of oxaliplatin for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens.
Authors: Sasaki Tohru , Azuma Mizutomo , Koizumi Wasaburo , Egawa Tomohisa , Nagashima Atsushi , Kenmochi Takeshi , Shimada Ken , Takinishi Yasutaka , Kobayashi Kouji , Saito Yusuke , Akatsuka Sotaro , Arioka Hitoshi , Nakayama Norisuke , Nishimura Ken , Takagi Seiichi , Shirahata Atsushi , Soda Hitoshi 
Published: February 2017

630 Background: Reintroduction of oxaliplatin seems to have clinical benefits for patients with metastatic colorectal cancer refractory to standard chemotherapy regimens. A interim analysis of RE-OPEN study reported 38.9% of disease control rate (DCR) in ASCO GI 2013, but it is still unknown who will receive benefits from reintroduction of oxaliplatin. Methods: Among patients in whom oxaliplatin was reintroduced in the 7 participating hospitals, we retrospectively studied patients who had previously received oxaliplatin and irinotecan and patients who had a response of stable disease or better during initial treatment with oxaliplatin. Results: From June 2009 through January 2013, oxaliplatin was reintroduced in 53 patients (31 men and 22 women). The median age was 64 years, and the performance status was 0 in 24 patients and 1 in 29. The reasons for discontinuing initial treatment with oxaliplatin were progressive disease in 36 patients, adverse events in 14 and others in 3. The response rate (RR), DCR, the median progression-free survival (PFS), and the median overall survival were 3.8%, 47.2%, 105 days, and 313 days, respectively. As for adverse events, allergic reactions to oxaliplatin (grade 1 or higher) occurred in 26% of the patients. RR, DCR, and PFS in 44 patients with the oxaliplatin-free-interval (OFI) over 6 months were 4.6%, 54.6%, and 119 days, respectively, and were statistically better than those in 9 patients with OFI less than 6 months (0%, 11.1%, and 84 days). Reintroduction of oxaliplatin with bevacizumab showed better PFS than that without bevacizumab (114 days and 78 days, respectively). Conclusions: Reintroduction of oxaliplatin was suggested to be one option for the management of colorectal cancer that is resistant to standard therapy, especially in patients with OFI over 6 months. Bevacizumab may enhance the results of reintroduction treatment.
Patterns of systemic therapy in metastatic colorectal cancer (mCRC): Use of intermittent and stop-and-go strategies in a population-based setting.
Authors: Cheung Winson Y. , Lim Howard John , Renouf Daniel John 
Published: February 2017

644 Background: The concept of treatment to disease progression must be tempered by the potential for cumulative toxicities of ongoing therapy. Data suggest that treatment holidays may provide improved quality of life without significantly compromising outcomes in metastatic disease. Our aim was to characterize the frequency of intermittent and stop-and-go strategies in a population-based cohort of mCRC patients. Methods: Patients diagnosed with mCRC and who received any palliative systemic treatment at the British Columbia Cancer Agency from Jan 2008 to Dec 2010 were identified from the provincial pharmacy database. First-line (1L) and second-line (2L) therapy choices, duration on each line of therapy, and number of treatment holidays, defined as any time interval of >/= 4 weeks without any therapy, were characterized. Results: In total, 946 patients were identified: median age was 64 (IQR 55-72) years, 521 (55%) were men, and 626 (66%) had colon cancer. In 1L treatment, the majority received combination systemic therapy: 474 (50%) FOLFIRI +/- bevacizumab (B), 224 (24%) FOLFOX +/- B, and 248 (26%) 5-FU/capecitabine. The median number of cycles on 1L therapy was 9 (IQR 4-13). Treatment holidays were common with 302 (32%) patients experiencing at least one break, each lasting a median of 49 (IQR 36-99) days. Compared with no B, 1L patients treated with B received more therapy (median 12 [IQR 8-20] vs 8 [IQR 4-12] cycles). However, they were also more likely to undergo a treatment holiday (34% vs 31%), but the duration of each break was shorter (median 49 [IQR 36-92] vs 56 [IQR 35-119] days). Only 312 (33%) out of the 946 patients proceeded to 2L therapy. The median interval between stopping 1L and starting 2L was 43 (IQR 20-162) days. Compared with 1L, the median number of treatment cycles was shorter in 2L (median 7 [IQR 4-12]). Treatment holidays were also less frequent with only 50 (16%) out of 312 patients experiencing at least one break, each lasting a median of 56 (IQR 38-100) days. Conclusions: The use of the stop-and-go approach was prevalent in this population-based cohort of mCRC patients. The relationship between intermittent treatment and outcomes will be presented at the meeting.
Outcomes after radiation therapy for brain metastases from gastrointestinal primaries.
Authors: Unger Keith Robert , Collins Brian Timothy , Marshall John , Pishvaian Michael J. , He Ruth , Collins Sean P. 
Published: February 2017

647 Background: There is limited data regarding outcomes of patients with colorectal cancer (CRC) and other gastrointestinal (GI) cancers metastatic to the brain. The aim of this study is assess intracranial disease control in GI patients treated with radiation therapy (RT) and the likelihood of receiving systemic therapy following the diagnosis of metastatic disease to the brain. Methods: From 1/2007 to 6/2013, 24 consecutive patients with adenocarcinoma of a GI primary were treated with RT for brain metastases. Patients were excluded if they had prior RT to the brain. The majority of patients had CRC (n = 15). Ten patients had resection of at least one brain tumor prior to radiation therapy. Patients were treated with the following RT modalities: stereotactic radiosurgery alone (n = 12), whole brain RT (n = 7), both (n = 1), and partial brain RT (n = 1). Survival and control rates were analyzed by the Kaplan-Meier method. Results: Twenty-one patients had died at the time of analysis and the median overall survival was 5.4 months (range, 0.5 – 58 months). Radiographic follow up was available in 20 patients and 60% (12/20) had intracranial disease progression. The 6- and 12-month control rates for the treated tumors were 60% and 30%, respectively. Seven patients received salvage radiation therapy following intracranial disease progression. Fifty-eight percent (14/24) did not receive further systemic therapy. On univariate analysis, only prior surgical resection predicted for improved survival (3.8 vs. 7.8 months, p = 0.018), while number of lesions, performance status, primary site, chemotherapy after RT, and RT modality were not significant. Conclusions: Survival and intracranial disease control following RT for brain metastasis from GI cancers are poor and many patients do not receive further systemic therapy. In this small series, outcomes are worse than published series for other disease sites metastatic to the brain and further research is warranted.