bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors associated with acute toxicity during chemoradiation therapy for rectal cancer.
Authors: Monpara Pooja , Rice Scott , Shaikh Talha , Farma Jeffrey M. , Sigurdson Elin R. , Denlinger Crystal Shereen , Dotan Efrat , Meyer Joshua E. 
Published: February 2017

734 Background: Acute toxicity may be a factor interfering with receipt of chemoradiation (CRT) therapy for rectal cancer. The purpose of this study was to identify clinical and treatment factors associated with increased acute toxicity in patients receiving CRT therapy for rectal cancer. Methods: We identified patients with rectal adenocarcinoma treated with CRT between 2006-2014 at an NCI-designated cancer center. Patients with metastatic disease or missing treatment information were excluded. Acute toxicity information including weight loss, pain, fatigue, constipation, diarrhea, anorexia, and performance status was extracted from weekly on treatment visit notes. Multivariable logistic regression was used to assess predictors of grade 3+ toxicity using covariates significant on univariable analysis. Results: A total of 148 patients were included with a median age of 59 (range 29-99). The majority of patients were male (55%) and received 5-FU based chemotherapy (82%). During CRT, 35 (24%) patients experienced at least one grade 3+ toxicity: 13 (9%) patients experienced grade 3+ fatigue, 1 (1%) experienced grade 3+ constipation, 11 (7%) experienced grade 3+ diarrhea, 14 (10%) experienced grade 3+ pain, and 11 (7%) experienced grade 3+ anorexia. Eight (5.4%) patients had an ECOG performance status > 3 and 28 (19%) patients had weight loss > 5 lbs during CRT. On multivariable analysis, increased distance from the anal verge (OR 0.78 95% CI 0.636-0.998) was associated with a decreased risk for grade 3+ pain and age > 75 was associated with an increased risk of grade 3+ anorexia (OR 6.07 95% CI 1.067-34.56). Clinical T4 disease was associated with an increased risk of weight loss > 5 lbs (OR 0.17 95% CI 0.100-0.446). On multivariable analysis, there were no factors associated with grade 3+ fatigue, diarrhea, or constipation. There were no factors associated with a decline in performance status to > 3 while on treatment. Conclusions: Our results suggest that rectal cancer patients who are older, have more advanced disease, or with low lying tumors may be at an increased risk for treatment-related toxicity. Identifying predictors of toxicity may allow for tailored interventions to minimize toxicity for these patients.
Efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for stage III colon cancer patients who underwent curative resection (KSCC1303).
Authors: Miyanari Nobutomo , Emi Yasunori , Tsuji Akihito , Sakai Kenji , Anai Hideaki , Takeshita Hiroaki , Imamura Hiroshi , Mori Shinichiro , Shimose Takayuki , Oki Eiji , Saeki Hiroshi , Kakeji Yoshihiro , Akagi Yoshito , Baba Hideo , Maehara Yoshihiko 
Published: February 2017

739 Background: Adjuvant chemotherapy is an accepted treatment method to improve the survival rate of Stage III colon cancer patients. Recently, regimens including oxaliplatin were proven superior to 5-FU only regimens. The purpose of this study was to examine the efficacy and feasibility of S-1 plus oxaliplatin (C-SOX) for Stage III colon cancer patients who underwent curative resection. Methods: Colon cancer patients who had undergone curative resection were enrolled in this study. They received oral S-1 40-60 mg twice daily on days 1 to 14 every 3 weeks plus intravenous oxaliplatin 130 mg/m2 on day 1 for 24 months. The primary endpoint was 3-year disease-free survival. The secondary endpoints were the rate of treatment completeness, adverse events, relative dose intensity, disease-free survival and overall survival. Results: Between 2014 February and 2014 December, eighty-nine patients were enrolled in this study. One patient had to be excluded due to ineligibility. The other eighty-eight patients were analyzed. The rate of protocol treatment completeness was 72.3%. Relative dose intensity of S-1 and oxaliplatin were 72 and 76.3, respectively. Hematological severe adverse events (Grade 3/4) were neutropenia (21.3%) and thrombocytopenia (15.7%). The most frequent symptom was diarrhea (Grade 3/4: 5.6%). Six-month disease-free survival rate was 94.3% (95% confidential interval: 86.9-97.6%). Six-month overall survival rate was 98.9% (95% C.I.: 92.2-99.8%). Conclusions: C-SOX for Stage III colon cancer patients who underwent curative resection was safe and feasible. The long-term outcome should be evaluated in future studies. Clinical trial information: 000012618.
Effects of adjuvant 5FU/oxaliplatin chemotherapy in individuals treated for colon cancer on cognitive and mobility function.
Authors: Lim Howard John , Niksirat Negin , Hung Stanley , Neil-Sztramko Sarah , Liu-Ambrose Teresa , Handy Todd , Hayden Sherri , Gill Sharlene , Campbell Kristin L. 
Published: February 2017

750 Background: Cognitive impairment has been reported for patients receiving chemotherapy; however, the data is limited with respect to 5FU/oxaliplatin based therapy in colorectal cancer patients. We conducted a pilot study to determine if there was cognitive or mobility impairment in patients receiving adjuvant 5Fu/oxaliplatin chemotherapy. Methods: At baseline, end of chemotherapy and 6 months post chemotherapy, participant completed a neuropsychological test battery, which included the Stroop, Hopkins Verbal Learning Test-Revised (HVLT-R), and Trail Making A & B (TMT A&B), a 6-minute walk test (6MWT), a measure of physical function, and a functional mobility testing battery, which included timed up and go (TUG) and gait speed. Demographic information and self-reported physical activity, using the International Physical Activity Questionnaire (IPAQ), were also collected at these time points. For the analysis of neuropsychological and mobility test scores, the paired t-test was used to test for the differences and assess the change in the mean scores from the baseline, 6-months and 12 months. Results: 13 patients were enrolled, 10 have completed the 12 month evaluation. No significant changes were noted in the HVLT-R, Stroop, and TMT-A and -B mean scores after completion of chemotherapy compared to baseline. Compared to baseline, no significant changes were observed for 6MWT, TUG, GS, or leisure-time physical activity after completion of chemotherapy. Conclusions: In this small pilot study, there were no significant changes in chemotherapy-associated cognitive, physical function, or functional mobility noted from baseline to the end of chemotherapy. In addition, physical activity levels and average time spent sitting did not change significantly.
The prognostic factor and the optimal timing of conversion surgery in unresectable stage IV gastric cancer: A retrospective analysis.
Authors: Sagawa Tamotsu , Okagawa Yutaka , Tamura Fumito , Hayashi Tsuyoshi , Fujikawa Koshi , Takahashi Yasuo , Sato Yasushi 
Published: February 2017

78 Background: Conversion surgery could be an option for unresectable stage IV gastric cancer when distant metastasis (M1) is disappeared by chemotherapy. However, the indication and the optimal timing of conversion surgery in stage IV gastric cancer remain unclear, even if metastatic lesions disappear with chemotherapy. Guideline of National Comprehensive Cancer Network also shows no principle after down-staging. Methods: This retrospective study examined 34 gastric cancer patients who underwent curative conversion surgery at our institute between 2005 and 2014. Clinicopathologic characteristics and patient outcomes were analyzed, with particular focus on the potential to select patients who might benefit from surgical resection. Results: The number of M1 factors was one in 31 patients and two in 3, including metastases to non-regional lymph node in 21, peritoneum in 8, liver in 5, and lung in 3. The regimen of chemotherapy was Docetaxel/CDDP/S-1 in 23 patients, Docetaxel/CDDP/S-1+Trastuzmab in 6, S-1/CDDP in 2, Docetaxel/S-1 in 1, CPT/CDDP in 1, and S-1 monotherapy in 1. The median duration from initiation of chemotherapy to the operation was 114 days (range 37-653 days). Total gastrectomy was performed in 27 patients and distal gastrectomy was performed in 7 patients. Complete resection with no residual tumor (R0) was achieved in 23 of 34 patients, microscopic residual tumor status (R1) in 10, and macroscopic residual tumor (R2) in 1. The 3-year overall survival (OS) rate among the patients who underwent conversion therapy was 58.0% with MST of 1190 days. Univariate analysis among the patents with conversion surgery identified intestinal differentiation, pathological response grade≧1b, R0 resection as significant prognostic factors. Patients operated on more than 91 days from initiation of chemotherapy had the 3-year survival rate of 68.2%, compared to 40.0% for patients operated on less than 90 days. Conclusions: Our data demonstrate the increased 3-year survival rate associated with delayed conversion surgery for stage IV gastric cancer. Delayed conversion surgery should be considered for patients, even if metastatic lesions disappear with chemotherapy.
Prognostic analysis of esophageal squamous cell cancer patients who received neoadjuvant chemoradiotherapy combined with surgery.
Authors: Li Xue , Hao Daxuan , Yang Yuanyuan , Zhang Yougai , Wu Xiaoyuan , Chen Yongshun , He Chunyu , Wang Wen , Liu Jinsong , Wang Jianhua 
Published: February 2017

97 Background: The neoadjuvant chemoradiotherapy (nCRT) combined with surgery is hopeful to improve the prognosis of locally advanced esophageal cancer but it remains contentious. Several studies showed that nCRT could significantly improve 5-year OS rate of locally advanced esophageal cancer. However, other clinical trials did not come to the same conclusion. This study retrospectively analyzed the esophageal squamous cell cancer (ESCC) patients who received nCRT combined with surgery in our hospital to investigate the prognostic factors for the patients’ survival. Methods: 96 patients with ESCC who received nCRT combined with surgery in our hospital from January 2007 to December 2014 were retrospectively analyzed. They were diagnosed with preoperation stage T3-4N0-1M0. Among them, 34 cases were in stage IIc and 62 cases were in stage IIIc. Prognostic factors for these patients were analyzed. Results: 26 (27.1%) patients received pathologic complete response (pCR) and 80 (83.3%) patients had downstage. The 1-, 3-, 5-year OS rates of all patients were 91.5%, 63.5%, 55.1%. The 1-, 3-, 5-year OS rates of tumor regression grading(TRG) 1, 2, 3 were 88.9%, 54.1%, 36.5% vs 88.4%, 56.4%, 48.6% vs 95.5%, 90.4%, 90.4%(Р = 0.014). The 1-, 3-, 5-year OS rates of pCR and non-pCR were 95.5%, 90.4%, 90.4% vs 88.6%, 55.6%, 45.4%(Р = 0.004). The 1-, 3-, 5-year OS rates of pathological lymph node negative(ypN-) and positive(ypN+) were 97.3%, 71.1%, 59.8% vs 66.7%, 33.3%, 33.3%(Р = 0.002). The 1-, 3-, 5-year OS rates of downstage and no-downstage were 94.9%, 73.9%, 65.6% vs 75.0%, 18.8%, 12.5% (Р = 0.000). Multivariate analyses identified pathologic lymph nodal status (RR = 2.193, 95%CI:1.018-4.726, Р = 0.045) and downstage category (RR = 3.520, 95%CI:1.638-7.568, Р = 0.001) were significant independent prognostic parameters. Conclusions: The nCRT combined with surgery achieved a high rate of long-term survival without increasing postoperative complications in patients with locally advanced ESCC. TRG was closely associated with patient’s prognosis, especially for patients with pCR. Pathologic lymph nodal status and downstage category were independent influencing factors for long-term survival.
Multicenter phase II study of neoadjuvant chemotherapy consisted with S-1 and oxaliplatin followed by gastrectomy for locally advanced gastric cancer.
Authors: Okita Yoshihiro , Satake Hironaga , Okuyama Hiroyuki , Kondo Masato , Miki Akira , Watanabe Takanori , Hatachi Yukimasa , Kotaka Masahito , Iwamoto Shigeyoshi , Kato Takeshi , Tsuji Akihito 
Published: February 2017

TPS180 Background: Prognosis for locally advanced gastric cancer, such as clinical T4 disease, bulky nodal involvement, type 4 and large type 3 gastric cancer, was not satisfactory even by D2 gastrectomy followed by adjuvant chemotherapy. Neoadjuvant chemotherapy is another promising approach. In our phase I study, neoadjuvant chemotherapy of S-1 and oxaliplatin (SOX) had manageable toxicities and good pathological complete response rate (33%) in patients with locally advanced gastric cancer. Based on the results of this phase I study, we initiate a multi-institutional, single-arm, open label, phase II study (Neo G-SOX PII study). The aim of this study is to evaluate the efﬁcacy and safety of the neoadjuvant chemotherapy of S-1 and oxaliplatin (SOX) followed by gastrectomy with D2/3 lymph node dissection; clinical T4; clinically resectable gastric cancer of type 4 or large type 3 (over 8 cm); bulky nodal involvement around major branched arteries to the stomach Methods: Eligibility criteria include histologically proven adenocarcinoma of the stomach; clinical T4; clinically resectable gastric cancer of type 4 or large type 3 (over 8 cm); bulky nodal involvement around major branched arteries to the stomach; resectable peritoneal dissemination (pathological CY1 or P1, except for clinical CY1 or P1). Patients receive two cycles of neoadjuvant chemotherapy with S-1 (80 mg/m2, p.o., days 1-14 followed by 1 week rest) and oxaliplatin (130 mg/m2 at day 1), followed by D2 or higher surgery with no residual disease. Patients with pathological R0/1 resection received S-1 (80 mg/m2, p.o., days 1-28 followed by 2 week rest) for 1 year as adjuvant chemotherapy. Primary endpoint is curative resection rate. Key secondary endpoints include pathological response, R0/1 resection rate, dose-intensity, overall survival, relapse free survival and safety. We set the threshold curative resection rate at 65% and the expected curative resection rate at 80%. Given a one-sided α of 0.1 and statistical power of 80%, 40 patients was required. Clinical trial information: UMIN000018661 Clinical trial information: UMIN000018661.
Pembrolizumab (MK-3475) versus paclitaxel as second-line therapy for advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma: Phase 3 KEYNOTE-061 study.
Authors: Ohtsu Atsushi , Tabernero Josep , Bang Yung-Jue , Fuchs Charles S. , Sun Linda , Wang Zhen , Csiki Ildiko , Koshiji Minori , Van Cutsem Eric 
Published: February 2017

TPS183 Background: Pembrolizumab (pembro) is a humanized monoclonal antibody against PD-1 that prevents PD-1 from interacting with PD-L1 and PD-L2 and permits activation of an antitumor immune response. In KEYNOTE-012, pembro showed a manageable safety profile and a 22% ORR in pts with advanced gastric cancer. The randomized, open-label, phase 3 KEYNOTE-061 study (NCT02370498) is designed to compare the efficacy and safety of pembro with those of standard-of-care paclitaxel in the second-line treatment of advanced gastric cancer. Methods: KEYNOTE-061 is designed for patients with metastatic or unresectable gastric or GEJ adenocarcinoma that progressed after first-line treatment with platinum and fluoropyrimidine doublet chemotherapy. Patients with HER2/neu-positive tumors are eligible if they have documented progression on a regimen that also included trastuzumab. Other key eligibility criteria include measurable disease per RECIST v1.1, ECOG PS 0-1, no chemotherapy within 2 wk of first dose of study drug, and provision of a newly obtained or archival tumor sample for assessing PD-L1 status. Eligible pts are randomized 1:1 to receive pembro 200 mg Q3W or paclitaxel 80 mg/m2 IV on days 1, 8, and 15 of each 28-d cycle. Treatment will continue until disease progression, intolerable toxicity, refusal by pt or investigator, or completion of 24 mo of therapy (pembro arm only). Pts in the pembro arm who have a CR after ≥ 24 wk may discontinue after ≥ 2 doses following initial CR. Clinically stable pts who progress per RECIST v1.1 may continue pembro at the discretion of the investigator until a confirmatory CT scan performed ≥ 4 wk later. Response will be assessed every 6 wk for the first 6 mo and every 12 wk thereafter per RECIST v1.1 by central review and per RECIST adapted for immunotherapy response patterns. AEs will be assessed throughout treatment and for 30 d thereafter (up to 90 d for serious AEs). Primary efficacy end points are PFS per RECIST v1.1 and OS in pts with PD-L1+ tumors. Secondary end points include PFS and OS in all pts, time to progression, ORR, and duration of response. Enrollment in KEYNOTE-061 is ongoing and will continue until up to 720 pts are enrolled. Clinical trial information: NCT02370498.
A pilot study of immune checkpoint inhibition (tremelimumab and/or MEDI4736) in combination with radiation therapy in patients with unresectable pancreatic cancer.
Authors: Duffy Austin G. , Makarova-Rusher Oxana V. , Pratt Drew , Kleiner David E , Alewine Christine , Fioravanti Suzanne , Walker Melissa , Carey Stephanie , Figg William Douglas , Steinberg Seth M. , Anderson Victoria , Levy Elliot , Krishnasamy Venkatesh , Wood Bradford J. , Jones Jennifer , Citrin Deborah E. , Greten Tim F. 
Published: February 2017

TPS470 Background: Tremelimumab is a fully human monoclonal antibody that binds to CTLA-4 expressed on the surface of activated T lymphocytes and causes inhibition of B7-CTLA-4-mediated downregulation of T-cell activation. MEDI4736 is a human monoclonal antibody directed against PD-L1. Blockage of ligation between PD-L1 and PD1 induces local immune activation and prevents anergy and exhaustion of effector T-cells. Several studies have documented an increase in peripheral antitumor immunity following radiation. This effect is evidently too weak to be clinically relevant, but has the potential to be boosted by immune modulation. The underlying hypothesis of this study is that the effect of immune checkpoint inhibition (accomplished via tremelimumab and/or MEDI4736) treatment can be enhanced by radiation in patients with advanced pancreatic carcinoma. Whilst radiation treatment in pancreas cancer is commonly employed in limited or early stage disease, if radiation can enhance the effect of immune checkpoint inhibition to produce systemic anti-tumor effects the combination could become an effective treatment modality for patients with advanced disease. Methods: Patients with histologically confirmed metastatic pancreatic cancer with primary in-situ (or locally-recurrent) disease are being enrolled to this pilot study. The primary objectives are to determine the safety, tolerability and feasibility of immune checkpoint inhibition [comprising either MEDI4736 alone (Cohort A), Tremelimumab (Cohort B) or combined MEDI4736 and Tremelimumab (Cohort C)] in combination with stereotactic body radiation therapy (SBRT) in patients with unresectable pancreatic cancer. Select eligibility criteria are as follows: at least 1 measurable metastatic lesion by RECIST 1.1 criteria and accessible for biopsy. No prior radiation therapy to the pancreas allowed. There is no limit to the number of prior chemotherapy regimens received; ECOG ≤ 1; Life expectancy of greater than 3 months. Acceptable organ and bone marrow function. No active or prior documented autoimmune or inflammatory disorders. Clinical trial information: NCT02311361.
Phase I dose escalation and pharmokinetic study of a modified schedule of 14-o-phosphonooxymethyltriptolide.
Authors: Greeno Edward , Borazanci Erkut Hasan , Gockerman Jon P. , Korn Ronald Lee , Saluja Ashok , VonHoff Daniel D. 
Published: February 2017

TPS472 Background: We are conducting a phase I trial of a modified dosing schedule of 14-O-phosphonooxymethyltriptolide (Minnelide,) a water-soluble prodrug of triptolide, a diterpene derived from the thunder god vine (tripterygium wilfordii). Triptolide is a potent inhibitor of heat shock protein 70 (HSP70) and pancreatic ductal adenocarcinoma over-expresses HSP70 as a protective mechanism. We have previously shown Minnelide to be effective and well tolerated in preclinical models of pancreatic carcinoma. We have previously presented our results from the initial phase I study of 27 patients using a daily dosing schema. That study demonstrated promising clinical activity with documented reductions in HSP70 levels. The common and dose limiting toxicity was neutropenia, which though cumulative, was also rapidly reversible early in the course of therapy with brief treatment interruptions. Several patients with disease control in the highest dose cohorts (0.67 and 0.8 mg/m2) progressed after dose reductions or prolonged treatment breaks mandated by the study protocol for cytopenias. Because of these observations we have revised the treatment schedule with short, early treatment breaks to allow more sustained therapy, and describe here the new study protocol. Methods: The study uses a 3+3 dose escalation scheme, enrolling subjects with gastrointestinal malignancies refractory to standard therapies. The drug is administered as a daily, brief IV infusion for 5 of 7 days for 3 weeks of a 4 week cycle. The initial dose cohort begins at 0.67mg/m2, above the MTD defined in the prior study and one step below the highest level achieved in our previous study of 0.8 mg/m2. The primary endpoint is toxicity, in order to define the MTD for this dosing schedule. Secondary endpoints being measured include: pharmokinetics of the study drug and its active metabolite triptolide; suppression of HSP70 levels; and tumor response. Cohort 1 at 0.67mg/m2 has been completed without DLT, enrollment to cohort 2 at 0.8mg/m2 is complete without DLT to date, and cohort 3 is anticipated to begin November of 2015. Clinical trial information: NCT01927965.
Randomized phase II study of the safety, efficacy, and immune response of GVAX pancreas (with cyclophosphamide) and CRS-207 with or without nivolumab in patients with previously treated metastatic pancreatic adenocarcinoma (STELLAR).
Authors: Le Dung T. , Crocenzi Todd S. , Uram Jennifer N. , Lutz Eric R. , Laheru Dan , Sugar Elizabeth A. , Vonderheide Robert H. , Fisher George A. , Ko Andrew H. , Murphy Aimee L. , McDougall Katherine , Ferber Sandy , Brockstedt Dirk G. , Jaffee Elizabeth M. 
Published: February 2017

TPS486 Background: A heterologous prime-boost vaccination strategy using GVAX pancreas and CRS-207 is showing promise in patients with pancreatic adenocarcinoma (PDA) (Le, JCO 2015). Furthermore, blockade of the immune checkpoint programmed death-1 (PD-1) is active in some cancers. Combinatorial strategies aimed at priming tumor antigen-specific T cells while simultaneously blocking negative checkpoints may be necessary to improve outcomes in PDA. GVAX is composed of allogeneic pancreatic cancer cells modified to express GM-CSF and induces a broad response against multiple tumor antigens. GVAX is given with low-dose cyclophosphamide (CY) to inhibit regulatory T cells. CRS-207 is live-attenuated Listeria monocytogenes engineered to express the tumor-associated antigen mesothelin. CRS-207 boosts responses against mesothelin and is unique in its capacity to stimulate both innate and adaptive immunity by activating T cells and NK cells. Nivolumab is an antibody against PD-1. Methods: This is a phase 2 study comparing CY/GVAX and CRS-207 with or without nivolumab in subjects with PDA who failed only one chemotherapy regimen for metastatic disease. Subjects are randomized in a 1:1 ratio to receive either 2 doses of CY/nivolumab/GVAX and 4 doses of nivolumab/CRS-207 (Arm A) or 2 doses of CY/GVAX and 4 doses of CRS-207 (Arm B). The primary objective is to compare OS between Arms A and B. Secondary/exploratory objectives include: assessment of safety and clinical responses (tumor assessments and CA19-9 levels) and correlation of Lm- and mesothelin-specific T cell and other immunological responses with OS, progression-free survival and best overall response. Clinical trial information: NCT02243371.