bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of an interactive electronic patient-reported outcome (e-PRO) system in outpatient with oral chemotherapy.
Authors: Rasschaert Marika Anna , Papadimitriou Konstantinos , Peeters Marc , Van den Brande Jan
Published: February 2017

696

Background: Health Information Technology (HIT) is increasingly integrated in clinical cancer care. Simultaneously routine assessment of patient reported outcomes (PROs) has been shown to reliably improve symptom management, identification of psychosocial problems and patient-provider communication. Methods: This study is a single center experience of a multicenter randomized study for the development and validation of an interactive e-PRO tool (RemeCoach). After obtaining informed consent, outpatients, using oral anti-cancer treatment, recorded their medication intake and 17 clinical parameters using this E-PRO tool. The device allowed real time data collection and communication with other care providers via a central platform. The registered data were processed by an algorithm, this algorithm stratifies the data into different grades according to international standards of care (CTCAE v4.0) and clinical importance. Patient clinical and demographic information is collected from medical records and analyzed using descriptive statistics. Results: 21 Patients were included, 62% male, mean age 59,2 (range 38-79). 38% Of patients used capecitabine, 52% regorafenib, 5% pazopanib and 5% sunitinib. Most common symptoms cited were fatigue (95%), myalgia and joint pain (75%) and cough (62%). Median pain score : 3 (Brief Pain Inventory(BPI)). Treatment compliance using the e-PRO was 75%. Conclusions: This study confirms the feasibility of the program, in an outpatient setting. This e-tool provides a means to register compliance, early symptoms of disease and toxicity of treatment.The compliance to the e-PRO tool will be confirmed, with further development of this program in a multicenter, randomized design. Evaluation of quality of life PRO-measurements and further exploration of the relationship between optimal pharmacovigilance and improvement of patient’s outcome will ensue.
Phase II trial of induction mFOLFOX6 plus bevacizumab followed by neoadjuvant S-1-based chemoradiation for MRI-defined poor-risk rectal cancer.
Authors: Konishi Tsuyoshi , Shinozaki Eiji , Murofushi Keiko , Ueno Masashi , Fukunaga Yosuke , Nagayama Satoshi , Fujimoto Yoshiya , Akiyoshi Takashi , Suenaga Mitsukuni , Matsusaka Satoshi , Chino Akiko , Kawachi Hiroshi , Yamamoto Noriko , Ishikawa Yuichi , Igarashi Masahiro , Oguchi Masahiko , Mizunuma Nobuyuki , Sano Takeshi , Yamaguchi Toshiharu
Published: February 2017

700

Background: Induction chemotherapy has been explored as a novel treatment option to improve oncological outcomes in poor-risk locally advanced rectal cancer (LARC). Although previous studies have suggested high pCR rate with a favorable toxicity profile in S-1-based neoadjuvant chemoradiation, no study has evaluated induction chemotherapy added with this regimen. The present study is designed to evaluate the safety and efficacy of induction chemotherapy with bevacizumab followed by neoadjuvant S-1 based chemoradiation in MRI-defined poor-risk LARC. Methods: This was a single-center phase II trial at a high-volume cancer center. Eligible patients had low rectal adenocarcinoma with MRI-defined poor-risk features. Patients received 12-week (6 course) mFOLFOX plus bevacizumab (5 mg/kg every 2 weeks) followed by concomitant oral S-1 (80mg/m2/day on days 1-5, 8-12, 22-27, and 29-33) plus radiotherapy (50.4Gy). Surgery was scheduled for 6-10 weeks after chemoradiation. Pathological complete response (pCR) was the primary endpoint. Results: A total of 43 eligible patients were enrolled. Forty-two patients (98%) completed induction chemotherapy. Forty-two patients (98%) completed planned radiation dose. One patient with cCR after completion of preoperative treatment declined surgery, but all the other 42 patients (98%) underwent R0 resection thorough a laparoscopic approach. A pCR was achieved in 16 patients (37%; 95% confidence interval 24.4%-52.1%). CTCAE grade 3 adverse events (AEs) occurred in 4 patients (9.3%) during induction chemotherapy and 5 patients (12%) during chemoradiation. There were no grade 4 AEs. Clavien-Dindo Classification grade III-IV surgical complications occurred in 6 patients (14%), including 1 grade IVa delirium, 1 grade IIIb anastomotic leakage, 1 grade IIIb bleeding, 2 grade IIIa pelvic abscess and 1 grade IIIa urethral fistula. There was no mortality. Conclusions: Induction FOLFOX plus bevacizumab followed by S-1-based chemoradiation achieved a high pCR rate with favorable toxicity and tolerable surgical complications in poor-risk LARC. Phase III trial is needed for further evaluation. Clinical trial information: UMIN000011457.
Gene expression profiling of Japanese gastric cancer patinets using Asian Cancer Research Group classification.
Authors: Terashima Masanori , Makuuchi Rie , Tokunaga Masanori , Tanizawa Yutaka , Bando Etsuro , Kawamura Taiichi , Hikage Makoto , Hatakeyama Keiichi , Oshima Keiichi , Ohnami Shunpei , Urakami Kennichi , Kusuhara Masatoshi , Yamaguchi Ken
Published: February 2017

72

Background: Gastric cancer is well known as having heterogeneous features. Recently, the Asian Cancer Research Group (AGRG) had proposed a new classification scheme based on the gene expression profile of the tumor. However, the genomi/expression profiling of gastric cancer in Japanese patients is still unknown. We started a comprehensive molecular profiling study that analyzes genome and transcriptome of tumor obtained from cancer patients admitted to Shizuoka Cancer Center from 2014. We already had evaluated more than 1,500 samples from various type of cancer. Among them, 104 gastric cancer patients were analyzed. Methods: Fresh surgically resected tumor/normal samples and peripheral blood were obtained and whole-exome sequencing (Ion Proton, Life Technologies) and gene expression profiling (DNA microarray, Agilent Technologies) were performed. Patients were grouped based on the gene expression profile according to AGRG classification, and clinicopathological features were compared among the group. Results: Patients were classified into MSI in 14, MSS/EMT in 15, MSS/TP53+ in 38 and MSS/TP53- in 37, respectively. There was no significant difference of sex among the group. Age was significantly younger in MSS/EMT and MSS/TP53-. In MSI, tumor tended to be located at antrum, and differentiated type tumor was predominant. In MSS/EMT, advanced T stage (T4) and undifferentiated type of tumor was predominant. In MSS/TP53+, relatively less advanced stage and localized macroscopic type tumor was predominant. In MSS/TP53-, relatively advanced stage and invasive macroscopic type tumor was predominant. Although the follow-up period is insufficient, relapse-free survival was the worst in MSS/EMT and no patient recurred in MSI. Conclusions: Classification of gene expression profiling based on ACRG was possible in Japanese gastric cancer. Distribution and tumor characteristics were almost identical to ACRG cohort. Gene -expression profiling may be comprehensively used for tumor classification and further clinical trials of molecular targeting agents.
A multicenter phase II study on the feasibility and efficacy of neoadjuvant chemotherapy for locally advanced rectal cancer.
Authors: Goto Saori , Hasegawa Suguru , Matsumoto Takuya , Hida Koya , Kawamura Junichiro , Yamanokuchi Satoshi , Yamaguchi Takashi , Matsusue Ryo , Kadokawa Yoshio , Kato Shigeru , Manaka Dai , Nishitai Ryuta , Nomura Akinari , Kanazawa Akiyoshi , Kawada Kenji , Kyogoku Takahisa , Sakai Yoshiharu
Published: February 2017

730

Background: The aim of this prospective multi-center phase II study was to evaluate the feasibility and efficacy of neoadjuvant chemotherapy (NAC) for locally advanced rectal cancer (LARC). Methods: Patients with LARC (cStage II–III) were included; those with cT4b tumor were excluded. Six cycles of mFOLFOX6 plus either bevacizumab (bev) or cetuximab (cet), depending on KRAS status, were administered before surgery. Primary endpoint was R0 resection rate. Secondary endpoints included completion rate of NAC, response rate, postoperative complications, pathological complete response (CR) rate, overall and disease-free survival, and quality of life. Results: Sixty patients from 7 institutes were enrolled. mFOLFOX6 was administered with bev to 40 patients who had wild-type KRAS and with cet to 20 patients who had K-RAS mutations. Completion rate of NAC was 88.4% and overall response rate was 81.7%. Sphincter-preserving surgery and abdominoperineal resection were performed in 43 and 17 patients, respectively. Median operation time was 335 min and median blood loss was 40 g. R0 resection rate was 98.3% and pathological CR rate was 16.7%. Overall postoperative complication rate ( ≥ grade 2) was 21.7%, including anastomotic leakage (11.6%), surgical site infection (6.7%), and urinary dysfunction (3.3%). There were no significant differences between patients with wild-type KRAS and those with KRAS mutations in response rate, postoperative complication rate, and pathological CR rate. Conclusions: NAC was a feasible and promising treatment option for LARC. Clinical trial information: UMIN000005654.
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.
Phase II study for determining usefulness of FDG-PET as imaging biomarker in regorafenib treatment for metastatic colorectal cancer (JACCRO CC-12).
Authors: Nakamura Masato , Satake Hironaga , Tsuji Akihito , Sagawa Tamotsu , Takagane Akinori , Sekikawa Takashi , Ichikawa Wataru , Oguchi Kazuhiro , Kaji Tomohito , Kochi Mitsugu , Fujii Masashi , Takeuchi Masahiro , Nakajima Toshifusa
Published: February 2017

TPS772

Background: Regorafenib (rego) is a novel multikinase inhibitor. A clinical, placebo-controlled phase III study (CORRECT) showed a 1.4-month improvement in Overall Survival (OS) as compared to the placebo group (HR 0.77, p = 0.0052) for metastatic colorectal cancer (mCRC). In the CORRECT trial, the Progression Free Survival (PFS) curve showed that half of the patients in the rego group showed a similar tendency to the placebo group. The finding suggested that patients might be divided into responders and non-responders, and there might be a biomarker to predict them. Although various studies including the CORRECT trial have searched for the biomarker of rego, it still has not been established. On the other hand, tumor metabolic analysis using FDG-PET has been reported to be more sensitive than the change of tumor size using CT to predict the response of molecular targeting therapies. We conducted a prospective multicenter phase II trial to identify the usefulness of FDG-PET as an imaging biomarker for rego. Methods: The main eligibility criteria are as follows; pathologically proven mCRC, sufficient organ functions, failure of standard therapies (fluorouracil, oxaliplatin, irinotecan and any biologic agents), with tumors detected by FDG-PET. The treatment schedule consists of 160mg once-daily oral administration of rego for 3 weeks, followed by 1 week of rest. On day 28, FDG-PET is re-taken and the change of the maximum standardized uptake value (SUVmax) from that of the pre-treatment examination is evaluated. The primary endpoint is the change of SUVmax in the region with the highest value in pretreatment FDG-PET. Secondary endpoints are changes of SUVmax in top 5 regions (maximum 2 regions in one organ), OS, PFS, response rate, disease control rate, adverse events, and correlation of their clinical parameters and changes of SUVmax. Because there has been no data about early change in SUVmax when rego was used, we set the threshold value and estimate value as 0% and 10%, respectively. Assuming a one-sided alpha of 2.5% and a power of ≥ 90%, 16 subjects are required, and a target sample size of 20 patients was determined. Ten of the planned 20 patients have been enrolled. Clinical trial information: UMIN000015563.
Cost comparison of treating low- and intermediate-risk endometrial cancer using time-derived, activity-based costing (TDABC) in a large regional cancer network delivery model.
Authors: Fleming Nicole D. , Lu Karen H. , Calhoun John D. , Jhingran Anuja , Arzu Isidora , Soliman Pamela T.
Published: February 2017

9

Background: Value-based and quality health care delivery has become an important focus for many health care systems. The purpose of this study was to assess the cost differences in treating low and intermediate risk endometrial cancer using time-derived activity based costing (TDABC) in a large regional cancer network model. Methods: Process mapping and TDABC was performed in treating endometrial cancer patients at a large tertiary cancer center (main) with a regional cancer network program. Clinical visits and adjuvant therapy including high-dose rate vaginal cuff brachytherapy (VBT) and pelvic radiation (PRT) were performed in ambulatory treatment centers at each location. Surgery for endometrial cancer was performed at the main cancer center. Costs for each process point was determine by cost-capacity rates, and compared by treatment center location. Results: TDABC costing determined a 28.3% cost difference in ambulatory clinic visits for endometrial cancer patients, favoring treatment at the regional network location. There was no cost difference in surgery for endometrial cancer patients since all procedures were performed at main. Delivering adjuvant VBT was 44.2% more in the ambulatory regional center compared to main, primarily due to the radiation quality assurance checks at the regional site. TDABC costing determined a 39.8% cost difference in delivering PRT for intermediate risk endometrial cancer patients, favoring treatment at the regional network location. Overall, there was a 13.2% cost savings, favoring treatment at the regional cancer network location. Conclusions: Delivering care for low and intermediate risk endometrial cancer in a regional network model may represent a cost effective health care delivery method. Quality assurance checks at the regional locations are required for quality treatment delivery, however, may represent an area for cost effective process improvements or need to stratify treatment location based on complexity.
Establishing a value framework for cancer-specific patient satisfaction (PS) across a large health system.
Authors: Holcombe Randall F. , Cartwright Frances
Published: February 2017

100

Background: The Mount Sinai Health System and the Tisch Cancer Institute (TCI) includes 7 hospitals and 6 ambulatory oncology centers in New York City, with over 9,000 new cancer cases seen annually. In order to address PS across these multiple sites, we established a framework to enhance value encompassing 4 domains: Infrastructure, Responsibility, Outcomes and Monitoring. Methods: Infrastructure. A quality dashboard was developed and distributed across all system sites. Inpatient oncology Dyads (D) (inpatient medical director and nurse manager) and ambulatory oncology Triads (T) (ambulatory medical director, nurse manager and administrator) and Quadrads (Q) (including radiation therapist) were established. Responsibility. DTQs at each location were given collective responsibility for PS performance. Outcomes. The relevant HCAHPS and Press-Ganey PS scores were defined across all groups; expectations for initiatives to improve PS were delineated. Monitoring. Each DTQ reported PS performance and progress on initiatives at a quarterly system-wide meeting of the TCI QI committee. Results: The quality dashboard provided a comprehensive PS report for all system sites and the DTQs identified specific individuals responsible for PS at each site. Within 6 months, establishment of the value framework more than doubled the number of quality initiatives, including ones focused on pain management, goals of care discussions and distress screening. Required participation in the TCI QI committee resulted in 100% compliance with reporting to a high level oversight group. Conclusions: The value framework involved the complete reorganization of how PS was reviewed, which individuals were responsible, and how initiatives to improve the patient experience were developed and monitored across the health system. Standardized dashboard-based reporting of PS facilitated review of critical information and creation of the DTQ structure facilitated engagement by key stakeholders, leading to numerous quality initiatives. Regular reporting elevated the level of attention ascribed to PS and the oversight group provided ongoing guidance for the process.
Development of an infusion nurse staffing model for outpatient chemotherapy centers.
Authors: Rodgers Georgina T.
Published: February 2017

103

Background: Nursing roles and responsibilities within ambulatory oncology infusion suites across our health system are not clearly defined and it is not understood what the appropriate staffing ratio should be per site. It is not clear if employees are working to the highest level of their licensure or skill, and if the appropriate activities are performed by the correct department. A standard staffing model to provide efficiency of clinical services and patient safety does not exist, and nursing roles are variable between the sites. Similar patient populations are being treated at each site and the variability of the roles introduces unnecessary costs to the system as a whole. The purpose of this project was to define roles of the infusion nurse to insure performance to the highest level of licensure, create efficiencies within the clinical setting, potentially reduce RN staffing requirements, achieve a cost savings, and develop a target nurse to patient ratio while maintaining quality care. Methods: Daily patient volume and hours of operation were compiled for each outpatient site and three methodologies were used to determine nurse to patient ratio. We utilized an acuity based ratio tool, hours per unit (HPU) method using billed charges for technical procedures and finally a simple 1:6 ratio based upon patient volume. Each methodology showed similar results and a final target ratio of 1:6 was chosen. Results: A staffing template was created to predict the number of RN’s necessary for treatment and an analysis of infusion sites was also completed to observe workflows and determine potential staffing adjustments. Our pilot site was initially staffed with 14 RN FTE’s and analysis showed many non-clinical, non-nursing duties were being performed by RN’s. Through process improvement we have created clear role delineation and the site currently functions with 5 RN FTE’s. We have maximized the efficiency of the nursing team, reduced costs, and there has been no decline or compromise in quality or patient safety. Conclusions: The implications of establishing this standard for infusion nursing has allowed us to duplicate the methodology across the health system and achieve a level of staffing that matches well with patient care needs.
Feasibility, acceptability, and efficacy of a proactive telephone intervention to improve toxicity management during chemotherapy.
Authors: Krzyzanowska Monika K. , McKay Cassandra , Han Heekyung , Gandhi Sonal , Laferriere Nicole Beatrice , Atzema Clare , Chan Kelvin K. , Howell Doris , Kukreti Vishal , Leung Yvonne , Pardhan Aliya , Mitchell Sandy , Nayer Marla , Pasetka Mark , Yao Jane , Redwood Erin
Published: February 2017

105

Background: Chemotherapy (chemo) is associated with a significant risk of toxicity, which often peaks between ambulatory visits. Consequently, effective remote symptom management support is essential to optimize self-management and resource use, including emergency department visits and hospitalizations (ED+H) during chemo. The aim of this study was to examine the feasibility, acceptability and effects of a telephone management intervention on symptomatic toxicity and resource use during chemo for early stage breast cancer (EBC). Methods: A prospective study of telephone-based toxicity management among women receiving neo-adjuvant or adjuvant chemo for EBC was undertaken at one urban and one rural site in Ontario, Canada. The intervention consisted of two standardized calls by nurses assessing common toxicities after each chemo (call 1 within 3 days and call 2 within 8-10 days). Primary outcome measures were feasibility and acceptability based on patient (pt) and clinician feedback. Efficacy was evaluated by self-reported ED+H. Results: Between 09/2013 and 12/2014, 77 women with EBC were enrolled (mean age 55 years). Most commonly used regimens were AC-paclitaxel (58%) and FEC-docetaxel (16%). 78% of pts received primary GCSF prophylaxis. Adherence with calls was 82%; mean call duration was 9 minutes. The intervention was well received by both pts and clinicians. 97% of pts indicated they liked receiving the calls and 94% would recommend this protocol be offered to all pts receiving chemo. Clinicians and pts felt the calls reduced pt anxiety by providing just-in-time education and counselling. Twenty five (33%) pts reported at least one ED+H during chemo, lower than the historical rate of 44% for this population in Ontario. Challenges included introducing an intervention that involved both routine clinical personnel and research staff and incorporating the calls into existing work responsibilities. Conclusions: Telephone-based toxicity management during ESB chemo is feasible, perceived as valuable by clinicians and pts, and may be associated with lower rates of acute care use. Larger scale evaluations of this approach focusing on effectiveness are warranted.
Using a disease pathway management approach to improve the quality of breast cancer care in Ontario.
Authors: Eisen Andrea , Soobrian Jasmin , Tyrrell Ashley , Li Clement , Muradali Derek , Forbes Margaret F , Gollnow Angelika , Ross Jillian , Holloway Claire ,   Cancer Care Ontario (CCO) Breast Cancer Pathway Working Group
Published: February 2017

109

Background: Disease Pathway Management (DPM) is used by Cancer Care Ontario (CCO) to set priorities for cancer control, plan cancer services, and improve the quality of care in Ontario by promoting standardization. The DPM approach applies a framework to examine the performance of the entire system from prevention to end of life care, and to identify any gaps within the system. In 2014, DPM began its breast cancer pathway initiative by mapping the patient journey, depicting evidence-based best practice along the breast cancer care continuum, identifying where further guidance is needed for clinical decision making, and identifying gaps in quality of care and performance measurement indicators. Objective: To evaluate the impact of DPM on quality assessment of breast cancer care in Ontario. Methods: DPM convened a multidisciplinary breast cancer working group (WG) of 40 experts from across Ontario. The WG held 12 meetings and used guidelines developed by CCO’s Program in Evidence Based Care (or other sources as needed) to generate pathways for the prevention, screening and diagnosis, treatment, and follow-up care for breast cancer. The pathways were used as a framework to review the existing inventory of provincial breast cancer quality indicators, and to identify areas where evidence based guidance is needed. The pathways were subjected to an extensive review process before publication. Results: The expert WG identified 28 priority areas, including opportunities to develop guidance in areas where it is lacking (e.g. role of perioperative breast MRI; indications for contralateral prophylactic mastectomy) and system barriers that may hinder optimal care (e.g. biomarker assessment). The WG also used the pathways as a framework for evaluating performance measurement indicators by mapping 48 existing quality indicators for breast cancer to the pathway. Conclusions: The CCO DPM Breast Cancer pathways facilitated a province-wide, multidisciplinary process to promote quality standards, to identify gaps and overlaps in performance and quality measurement, and to recommend additional indicators more relevant to the quality of breast cancer care in Ontario.