bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of cabozantinib in patients (pts) with relapsed or refractory metastatic urothelial carcinoma (mUC).
Authors: Apolo Andrea Borghese , Parnes Howard L. , Madan Ravi Amrit , Gulley James L. , Wright John Joseph , Hoffman-Censits Jean H. , Dawson Nancy Ann , Trepel Jane B. , Khadar Kattie , Schlom Jeffrey , Merino Maria , Raffeld Mark , Steinberg Seth M. , Choyke Peter L. , Lindenberg Maria Liza , Folio Les , Agarwal Piyush K. , Figg William Douglas , Bottaro Donald P. , Dahut William L. 
Published: February 2017

307 Background: Translational studies have shown that shed MET levels in serum and urine of pts with UC correlate with stage and visceral metastases and that cabozantinib reverses HGF-driven UC cell growth and invasion. These data support the evaluation of cabozantinib in pts with mUC. Methods: In this phase II study, pts receive cabozantinib 60 mg daily in 28-day cycles. There are 3 study cohorts (1) mUC, (2) bone only mUC (3) metastatic rare bladder histology. The primary objective is to determine the response rate (RR) by RECIST. Response is assessed every 2 cycles. Tissue, blood, and urine were collected on all pts to test for MET/HGF and immune subsets. Results: 26 out of 55 pts have enrolled (19 M, 7 F): median age 62 (42-82) and median KPS of 80%. Primary sites include bladder (77%) and upper tract UC (23%). Prior therapy includes 30% pts with 1 regimen, 39% with 2, 15% with 3, 8% with 4 and 8% with 6. 81% of pts had visceral metastases (lung, liver and bone) and 19% lymph node only metastases. 23 pts (19 in cohort 1, 3 in cohort 2 and 1 in cohort 3) were evaluable for response after completing at least 4 weeks of therapy. In cohort 1, 2 pts achieved PR (1 remained on study for 10 months and 1 remains on study after >12 months of therapy); 7 pts had SD for at least 16 weeks (1 remained on study for 11 months); 10 had PD; 1 is too early to assess for response; 1 was removed before restaging for toxicity and 1 was removed for not meeting eligibility. The objective RR is 11% and SD 37% for a clinical benefit of 48%. In cohort 2, 1 of 3 pts had a near resolution of bone lesions on NaF PET/CT for 11 months. In cohort 3, only pt enrolled (squamous cell carcinoma of the bladder) achieved SD for 16 weeks. Mixed responses with regression of lung, bone or lymph nodes were observed in 30% of pts with PD. Grade 3/4 toxicities included: fatigue (8%), hyponatremia (8%), hypophosphatemia (8%) diarrhea (4%), thromboembolism (4%), transaminitis (4%), hypothyroidism (4%), thrombocytopenia (4%), dysphonia (4%), hypomagnesemia (4%), creatinine increase (4%) and proteinuria (4%). Conclusions: Cabozantinib has clinical activity in pts with relapsed or refractory mUC with manageable toxicities. Further studies are underway to correlate response to therapy with MET expression. Clinical trial information: NCT01688999.
Results of a randomized controlled study of personalized care plans in breast cancer survivors from a single institution.
Authors: Haq Rashida , Brezden-Masley Christine , Lee Ronita , Richter Suzanne , George Ralph L. , Simpson Jory , Rackal Julia , Leung Fok Han , Jovicic Aleksandra , Kong Amy , Li Benjamin , Gulasingam Pauline , Jainudeen Tara 
Published: February 2017

109 Background: In 2006, Institute of Medicine recommended care plans for coordination of care of cancer survivors. Our pilot study of multifaceted care plans met information and communication needs of breast cancer (BC) survivors and their primary care providers (PCP). In this study, a Personalized Multifaceted Care Plan (PMCP) was developed, implemented and evaluated. Methods: This was a randomized study with mixed methods design. Upon REB approval, 78 women diagnosed with invasive BC for adjuvant treatments were recruited from the breast clinic from June 2013 to March 2015. After informed consent, participants were randomized to the control or the intervention group and stratified to chemotherapy (CT) vs. endocrine therapy (ET). The intervention group received a PMCP (paper based treatment and care plans (TP & CP) with information on breast pathology, treatment sequence, supportive care and follow-up guidelines with access to a website). CT arm patients received a TP at the start of therapy and a CP at completion. ET patients received the CP upfront. Quantitative outcomes were assessed by 3 standardized questionnaires at baseline and following treatment. Within-group baseline and post-intervention scores were compared using paired t-tests. The post-intervention control group and intervention group’s scores were compared using unpaired t-tests. In the intervention group, qualitative analysis was done through focus groups of BC survivors & PCP interviews. Results: Baseline scores in the mean intervention and control groups were similar. In the CT arm of the intervention group, post-intervention scores on Communication and Efficacy Scale showed statistically significant increase (p < 0.05, 95% CI). Results in the control group and in the intervention group of patients on ET were not significantly different. Focus group participants commented that the PMCP helped them feel ‘educated’ and engaged in their cancer treatment and their PCPs found the PMCP contained useful, concise medical summaries. Conclusions: Upfront PMCP improves self-efficacy scores in patients on CT. Qualitative analysis substantiates the benefits of PMCP. PMCP should be standard of care in BC survivors receiving CT.
End-of-life cancer care: Health service delivery in the last 12 months of life in Calgary, Alberta, Canada.
Authors: Kerba Marc , Sinnarajah Ayn , Rose M Sarah , Nicholson Lynn , Wheler Barbara , Enns Bert ,   The Calgary Zone Palliative Care Collaborative
Published: February 2017

171 Background: In Calgary, Alberta, the Calgary Zone Palliative Care Collaborative (CZPCC) undertook a study to examine the current state of cancer and palliative services and to recommend steps to address gaps in service delivery. We hypothesized that early access to palliative care services would reduce utilization of active cancer treatments and services for individuals nearing the end of life. Our study objectives were to determine the utilization and timing of acute, palliative and oncology-related services in Calgary. Methods: This retrospective study examined cancer registry and administrative data for patients > 18 years, who died in 2012. Measures of aggressive end of life care (EOL) were also collected. A combination of descriptive statistics, tests of association and multivariate regression analysis were conducted. Results: N = 1909 died of cancer in 2012: median age 73 years (IQR: 62-82 years) and median disease duration 364 days (IQR: 92-1114 days). 40.6% of patients received systemic treatment in last 12 months of life. 29.9% received radiotherapy and 13.0% received psychosocial/spiritual care. Palliative care contact was 80.7%, inclusive of 20.6% who had an intensive palliative care unit admission. 5.2% had EOL chemotherapy and 3.8% received EOL radiotherapy. Up to 10.4% of patients had one or more hospital admission. There was no significant effect of age on those who received aggressive EOL care. Men had an increased probability to receive aggressive EOL care (p = 0.015). Tumor group was also associated with receiving aggressive EOL (p < 0.001), with the highest utilization in Head and Neck and hematological malignancies. In patients with a disease duration of > 4 months those who received palliative care at least 2-3 months prior to death were less likely to receive aggressive EOL care (P < 0.001). Patients whose disease duration was < 1 month were less likely to receive aggressive EOL care if they received palliative care services (p = 0.02). Conclusions: The provision of palliative care services at the end of life is most needed among men and certain tumor groups who are the highest users of aggressive EOL care.
Determination factors of patients' decision between surgery and chemoradiotherapy for stage I esophageal carcinoma: From the results of JCOG0502—A comparative study of the two modalities.
Authors: Kato Ken , Igaki Hiroyasu , Ito Yoshinori , Nozaki Isao , Daiko Hiroyuki , Yano Masahiko , Udagawa Harushi , Nakagawa Satoru , Takagi Masakazu , Okabe Hiroshi , Abe Tetsuya , Okuno Tatsuya , Hihara Jun , Toh Yasushi , Akutsu Yasunori , Shibuya Yuichi , Mizusawa Junki , Nakamura Kenichi , Fukuda Haruhiko , Kitagawa Yuko ,   Japan Esophageal Oncology Group of Japan Clinical Oncology Group (JCOG)
Published: February 2017

114 Background: Surgery is the standard of care for stage I esophageal squamous cell carcinoma. However, definitive chemoradiothearpy (CRT) is optional treatment which can preserve organ function with cure. The aim of this study was to investigate what factors have influence patients(pts)’ decision on the treatment, surgery or CRT. Methods: JCOG0502 is a randomized controlled trial comparing surgery to CRT. Sufficient information about both treatments was provided for pts before enrollment. Pts who declined to participate in randomized part can choose a preferred treatment and join a non-randomized part of JCOG0502. Between Dec 2006 and Feb 2013, 379 pts were enrolled to JCOG0502 from 37 institutions of Japan Clinical Oncology Group. Among those, 368 pts who enrolled to non-randomized part were analyzed. Clinical baseline data, social data and doctor’s preference which was not mandatory informed to patients were collected on the case report forms and compared between surgery arm and CRT arm. Preference of doctors for each pt was divided into three categories, A: “surgery is preferred”, B: “either is adequate” and C: “CRT is preferred”. This trial was registered as UMIN000000551. Logistic regression were performed to evaluate the influence of each factors. Results: Of the 368 pts, 209 pts chose surgery with their own intention, while 159 pts chose CRT. There were no differences on baseline clinical characteristics between two groups except median age (Surgery: CRT = 62:65 years). Multivariate logistic regression analyses showed that >=65 years (vs<65) (OR 2.04, p=0.006), male (vs female) (OR 2.10, p=0.043), multi-focal primary (vs single) (OR 2.76, p=0.013), status of patient’s children (vs presence of children) (absence of children: OR 2.27, p=0.034) (unknown: OR 4.422, p=0.13), and B or C category of preference of the doctor (vs A) (B:OR 11.67, p<0.001)(C:HR 29.64, p<0.001) were associated with selection of CRT. Conclusions: Older age, male, multifocal primary, absence of children and doctor’s preference are independent factor to choose CRT. Doctor’s preference to each pt was the strongest factor on decision making of patients.
Prognostic factors in locally advanced, unresectable esophageal cancer patients treated with chemoradiotherapy (exploratory analysis of JCOG0303).
Authors: Okuno Tatsuya , Mizusawa Junki , Kato Ken , Shinoda Masayuki , Katayama Hiroshi , Igaki Hiroyasu , Tsubosa Yasuhiro , Kojima Takashi , Okabe Hiroshi , Kimura Yusuke , Kawano Tatsuyuki , Kosugi Shinichi , Toh Yasushi , Kato Hoichi , Nakamura Kenichi , Fukuda Haruhiko , Ishikura Satoshi , Ando Nobutoshi , Kitagawa Yuko ,   Japan Esophageal Oncology Group of Japan Clinical Oncology Group (JCOG)
Published: February 2017

150 Background: The prognosis of patients (pts) with locally advanced esophageal squamous cell carcinoma (LAESCC) is generally dismal. Definitive chemoradiotherapy (CRT) with cisplatin plus 5-fluorouracil (CF-RT) is the standard treatments especially for the pts with unresectable LAESCC. The aim of this study is to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) in the pts with unresectable LAESCC treated with CRT. Methods: 142 patients were enrolled to JCOG0303, and assigned to standard CF-RT group and low-dose CF-RT group. 131 pts with sufficient data were used for this analysis. Cox regression model was used for an analysis of prognostic factors of the pts with unresectable LAESCC treated with CF-RT. GPS was classified by baseline CRP and serum albumin. Pts with a CRP ≤ 1.0 mg/dL and albumin ≥ 3.5 g/dL were allocated to GPS0 group. If only CRP was increased or albumin decreased,pts were allocated to the GPS1 and pts in whom CRP was > 1.0 mg/dL and albumin level < 3.5 g/dL were classified as GPS2. Results: The pts background was as follows: median age (range), 62 (37-75), male / female, 119/12; ECOG PS 0/1/2, 64/65/2; clinical stage (UICC 6th) IIB/III/IVA/IVB, 3/75/22/31. As a result of multivariable analysis including all variables, the factors which became statistically significant were shown in the table. In several sensitivity multivariate analyses, only esophageal stenosis was indicated as a common poor prognostic factor. In addition, overall survival tended to decrease according to GPS subgroups (median survival time(m): GPS0/GPS1/GPS2 16.1/14.9/8.7). Conclusions: Presence of stenosis was thought to be one of the candidates for stratification factor in randomized trial for unresectable LAESCC pts. Furthermore, GPS represents a prognostic fator in LAESCC pts treated with CRT. Clinical trial information: 000000861. [Table: see text]
Baseline demographics of the randomized, placebo-controlled, double-blind, phase III RADIANT-4 study of everolimus in nonfunctional gastrointestinal (GI) or lung neuroendocrine tumors (NET).
Authors: Yao James C. , Buzzoni Roberto , Carnaghi Carlo , Fazio Nicola , Singh Simron , Wolin Edward M. , Tomasek Jiri , Raderer Markus , Lahner Harald , Lam Du Hung , Cauwel Helene , Valle Juan W. , Delle Fave Gianfranco , Van Cutsem Eric , Strosberg Jonathan R. , Tesselaar Margot Et , Shimada Yasuhiro , Oh Do-Youn , Kulke Matthew , Pavel Marianne E. ,   The RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial (RADIANT-4) Study Group
Published: February 2017

276 Background: NET are malignant tumors arising from neuroendocrine cells throughout the body. Everolimus (EVE), a mammalian target of rapamycin inhibitor, is approved for the treatment of advanced, well-differentiated pancreatic NET. There is an unmet medical need in GI and lung NET; targeted therapies, such as everolimus, are of particular interest. Methods: Patients with advanced nonfunctional NET of GI or lung origin with progressive disease (PD) within the past 6 months were randomized (2:1) to EVE 10 mg/d or placebo, both with best supportive care. Concomitant use of somatostatin analogue (SSA) was not allowed during the study, except for control of emergent carcinoid symptoms not manageable by standard therapy. Patients were stratified based on tumor sites, prior SSA exposure, and WHO performance status (PS) at baseline. Primary endpoint was progression-free survival (PFS) as assessed by central radiology review using modified RECIST 1.0 criteria. Primary analysis is planned after ~176 PFS events. Crossover to open label EVE after progression would not be allowed prior to the primary analysis. Overall survival was the key secondary endpoint. Results: Recruitment is completed. Of 388 patients screened, 302 were randomized (planned, 285). Median age was 63 years, 53% were females, and majority of them (76.2%) were white. The most common tumor sites were lung (29.8%), ileum (23.5%), and rectum (13.2%). WHO PS was 0 in 219 (72.5%) patients and 1 in 82 (27.2%) patients; 52% had received SSA prior to study entry. As of Sep 16, 2013, 173 (57.3%) patients remain on treatment, 127 (42.1%) discontinued treatment and 2 (0.7%) were not treated. PD (24.2%) and adverse events (10.6%) were the most common reasons for treatment discontinuation. Results of primary analysis are expected by early 2015. Conclusions: RADIANT-4 is the first phase III study to assess the efficacy and safety of EVE in patients with nonfunctional NET of GI or lung origin. Non-crossover design and prospective stratification of the population based on known prognostic factors should minimize confounding in the estimation of the treatment effect. Clinical trial information: NCT01524783.
A multicenter randomized, open-label, proof-of-concept, phase II trial comparing gemcitabine with and without IMM-101 in advanced pancreatic cancer.
Authors: Dalgleish Angus George ,   The IMAGE I Trial Investigators
Published: February 2017

336 Background: Immunotherapy is becoming established as an effective way of treating cancer. Immodulon Therapeutics is developing IMM-101, a heat-killed whole cell preparation of Mycobacterium obuense (NCTC 13365), which modulates systemic immune responses, as an adjunctive immunotherapy for pancreatic cancer. Methods: Patients with advanced pancreatic cancer and a WHO score of 0-2 were assigned randomly to receive IMM-101 (0.1 mL intradermal injection of 10 mg/mL) plus Gemcitabine (Gem) (1000 mg/m2for 3 consecutive weeks out of 4) or Gem alone. Per protocol, this could be continued to a 12-cycle maximum. The primary efficacy endpoint was overall survival (OS). Safety, tolerability and progression free survival (PFS) were also assessed. Results: A total of 110 patients were randomized, 75 to receive IMM-101 plus Gem and 35 Gem alone (ITT population). The PP population consisted of 63 and 35 patients, respectively. Conclusions were similar; here we report results of the PP analysis. Median OS was increased significantly by 29% to 7.2 months in the IMM-101 plus Gem group compared to 5.6 months in the Gem group (p=0.022; HR 0.60, 95% CI 0.38-0.94). Median PFS was increased significantly by 83% to 4.4 months in the IMM-101 plus Gem group compared to 2.4 months in the Gem group (p=0.003; HR 0.51, 95% CI 0.32-0.81). In the pre-defined sub-group of patients with metastatic disease (n=82), median OS was increased significantly by 70% to 7.5 months in the IMM-101 plus Gem group (n=54) compared to 4.4 months in the Gem group (n=28) (p=0.002; HR 0.46, 95% CI 0.28-0.76). A highly significant 91% increase in median PFS from 2.3 months in the Gem group to 4.4 months in the IMM-101 plus Gem group was observed (p<0.001; HR 0.40, 95% CI 0.24-0.66). IMM-101 was well tolerated. The only adverse events of NCI CTC ≥Grade 3 occurring more frequently in the IMM-101 group (absolute difference in frequency between the groups >5%) were asthenia 10.8% and abdominal pain 8.1% (both 2.9% in the Gem group). Conclusion: Clinically meaningful increases in OS and PFS were demonstrated with IMM-101. No additional burden of adverse events above those relating to chemotherapy or the underlying disease was observed. Clinical trial information: NCT01303172.
Quality-adjusted survival in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC) receiving first-line therapy with panitumumab plus FOLFOX versus FOLFOX alone in the PRIME trial.
Authors: Wang Jianmin , Dong Jun , Johnson Patrick , Maglinte Gregory A. , Rong Alan , Barber Beth L. , Douillard Jean-Yves 
Published: February 2017

537 Background: The pivotal phase III PRIME trial demonstrated that, compared with FOLFOX alone, panitumumab plus FOLFOX prolongs overall survival and progression-free survival in patients with RASWT mCRC without having a detrimental effect on overall quality of life. The objective of this analysis was to use the quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) method to compare quality-adjusted survival between the treatment arms of PRIME. Methods: Patients with RASWT mCRC from each treatment arm of PRIME were included in this analysis, and the area under the survival curve (AUSC) was estimated using the nonparametric Kaplan-Meier method (48 months follow-up). The AUSC was partitioned into three health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST, i.e., PFS minus TOX), and relapse (REL, i.e., OS minus PFS). The durations of the health states were then adjusted using utility weights derived from patient-reported EuroQoL 5 measures. The null hypothesis of no difference between treatment arms was tested based on the normal approximation, with standard errors calculated by the bootstrap method. In the primary analysis, TOX consisted of grade 3 and 4 adverse events. A sensitivity analysis, with grade 2, 3, and 4 adverse events classified as TOX, was performed. Results: Of 1,183 patients with mCRC who were randomized, 512 patients had RAS WT tumors (panitumumab plus FOLFOX, n=259; FOLFOX alone, n=253) and were included in this analysis. Patients receiving panitumumab plus FOLFOX had a significantly longer Q-TWiST (20.5 months) than patients receiving FOLFOX alone (18.2 months) resulting in 2.3 ± 1.0 (SE) additional quality-adjusted months (p<0.03). The sensitivity analysis yielded similar results, indicating that the analysis was robust. Conclusions: This Q-TWiST analysis showed that in a previously untreated RAS WT mCRC population, patients treated with panitumumab plus FOLFOX had a significantly improved duration of quality-adjusted survival compared with patients treated with FOLFOX alone. Clinical trial information: NCT00364013.
Next-generation sequencing (NGS) in metastatic gastrointestinal cancer (mGIC) patients: Translation from sequence data into clinical practice.
Authors: Moreira Raphael Brandao , Alessandretti Matheus Bongers , Abrahao Carina Mina , Lino Aline Da Rocha , Sousa Tarcia Tarciane Soares de , Amarante Marcus Paulo Fernandes , Gomes Jessica Ribeiro , Martins Junior Rodnei Merlrina , Carvalho Rafael Ferreira de , Kawamura Haddad Carolina , Schutz Fabio Augusto Barros , Peixoto Renata D'Alpino , Cruz Marcelo Rocha , Maluf Fernando C. , Buzaid Antonio C. ,   COAEM
Published: February 2017

72 Background: A considerable number of patients with mGIC progress after exhausting all approved standard therapies but maintain an adequate performance status and could be candidates for further treatment. We aim at reviewing our experience with the use of a NGS platform in refractory mGIC and its clinical utility. Methods: We retrospectively reviewed demographics, NGS results, and the suggested therapies received by patients undergoing NGS (Foundation Medicine, Cambridge, MA, USA): exonic sequencing of 236 genes and selective intronic sequencing from 19 genes for refractory mGIC. Co-primary endpoints were the percentage of patients with targeted therapy options uncovered by mutational profiling and the percentage of them who received genotype-directed therapy. Results: Samples from 32 patients were tested. Primary tumors consisted of colorectal adenocarcinoma (37,5%), pancreatic adenocarcinoma (31,2%), gastric adenocarcinoma (12,5%), cholangiocarcinoma (12,5%) and hepatocellular carcinoma (6%). Most patients (87,5%) were found to harbor potentially actionable genetic alterations involving mitogen-activated protein kinase (93,7%), phosphatidylinositol 3-kinase-AKT (18,7%), p53 (50%) and cell-cycle regulation (9%) pathways. Of the 6 patients who received the suggested targeted therapy, 4 achieved an objective response. Conclusions: Mutational profiling using a targeted NGS panel identified potentially actionable alterations in the majority of advanced gastrointestinal cancer patients. The assay provided clinical benefit in 12% of the patients.