tbuckley/cabot-search huggingface dataset:
A single arm, prospective multicenter phase II study FOLFIRINOX in patients with advanced and recurrent biliary tract cancer.
Authors: Naminatsu Takahara, Hiroyuki Isayama, Yousuke Nakai, Tatsuya Ioka, Masashi Kanai, Takashi Sasaki, Junji Furuse, Kazuhiko Koike
Journal: Journal of Clinical Oncology (2017)

TPS514 Background: The current standard of care for patients with advanced biliary tract cancer (BTC) is gemcitabine and cisplatin (GC) combination chemotherapy. Despite intensive researches, no trials have proved better overall survival (OS) over GC. Recently, FOLFIRINOX provided a remarkable survival benefit over gemcitabine in patients with metastatic pancreatic cancer. Given the promising results of FOLFIRI and FOLFOX in patients with advanced BTC, FOLFIRINOX can be an attractive option in patients with advanced BTC as well. Methods: This is a single-arm, open-label, multi-center phase II study to evaluate the safety and efficacy of FOLFIRINOX in patients with advanced BTC. The major inclusion criteria are as follows; unresectable or recurrent BTC, histologically or cytologically confirmed adenocarcinoma, no prior chemotherapy or radiation therapy, age of 20-75 years, an ECOG PS of 0 or 1, at least one measurable lesion, adequate hematological, liver and renal function. The major exclusion criteria are as follows; UGT genetic polymorphisms of homozygous UGT1A1*6 or *28 or heterozygous UGT1A1*6 and *28, massive pleural effusion or ascites. FOLFIRINOX consists of oxaliplatin of 85 mg/m 2 , irinotecan of 180 mg/m 2 , leucovorin of 400 mg/m 2 administered by intravenous infusion and fluorouracil of 400 mg/m 2 by intravenous bolus and of 2,400 mg/m 2 by continuous intravenous infusion every 2 weeks. The primary outcome is progression-free survival (PFS), and the secondary outcomes are OS, tumor response and safety. PFS and OS will be calculated from the date of enrollment until the date of documentation of disease progression or death in patients without disease progression and the date of death. Tumor response will be evaluated according to the RECIST version 1.1 every 2 months. Safety will be evaluated with the CTCAE version 4.0. A total of 35 patients will be required to provide 75% power to detect an increase in median PFS from 6 months provided by standard care of GC to 10 months in patients receiving FOLFIRINOX, with a 24 months of recruitment and 18 months of follow-up. A phase III trial will be considered when this study shows the lower limit of the 80% confidence interval for PFS is longer than 6 months. Clinical trial information: UMIN000020801.
γ-synuclein expression in ovarian cancer.
Authors: Kristina Mori, Stacey Akers, Wiam Bshara, Barbara Buttin, Peter J. Frederick, Irene B. Helenowski, Carl D Morrison, Kunle Odunsi, Julian C. Schink, Denise M. Scholtens, Jian-Jun Wei, J. Julie Kim
Journal: Journal of Clinical Oncology (2013)

5574 Background: γ-synuclein (SNCG) expression is associated with advanced disease and chemo-resistance in multiple solid tumors. Our goal was to determine if SNCG expression in ovarian cancer was correlated with clinicopathologic variables and patient outcomes. Methods: Tissue microarrays from primary tumors of 358 ovarian, fallopian tube, and primary peritoneal cancer patients, who underwent primary surgery at Roswell Park Cancer Institute between 1995 and 2007 were constructed and stained for SNCG. A blinded pathologist scored tumors as positive if ≥10% of the sample stained. Medical records were reviewed for clinicopathologic and demographic variables. Between the positive and negative groups, Wilcoxon rank-sum test was used to compare the median ages and Fisher’s exact test was used to compare groups in categorical variables. Cox proportional hazard models were used to determine associations between SNCG and overall (OS) and progression-free survival (PFS). Results: The median follow-up was 36 months, median OS was 39 months, and median PFS was 18 months. SNCG presence was significant in patients with serous histology, grade 3 disease, suboptimal debulking, ascites at surgery, FIGO stage III-IV cancer, or initial CA-125 level &gt;485. There was no significant difference in OS (HR 1.06 95% CI 0.81-1.39 P 0.69) or PFS (HR 1.16 95% CI 0.89-1.50 P 0.28) for patients with SNCG expression. Conclusions: SNCG expression in ovarian cancer is more frequent in patients with high-risk features, but it does not correlate with chemotherapy response, OS, or PFS. [Table: see text]
Willingness of cancer patients to discuss advance directives with admitting doctor or oncologists
Authors: L. A. Dow, T. J. Smith, R. Matsuyama, E. B. Lamont, V. Ramakrishnan, L. Kuhn, L. Lyckholm
Journal: Journal of Clinical Oncology (2009)

9539 Background: Many seriously ill cancer patients do not discuss prognosis or advance directives (ADs), which may lead to aggressive care at end of life (Harrison &amp; Smith, JAMA 2008). Ten years ago, cancer patients did not want to discuss ADs with their oncologist (ONC), but would discuss them with an admitting doctor (Lamont JPM 2000).We assessed if this still held. Methods: We administered semi-structured interviews to cancer inpatients on the VCUHS Hematology-Oncology service. 55/63 consecutive patients accrued. Information was collected regarding ADs and knowledge of hospice/palliative care. Results: Of those enrolled, 22/55 (40%) reported having ADs. Only 2/55 had discussed ADs with their oncologist. Only 12/55 (22%) would want to discuss ADs with their ONC. But when specifically asked, 22/55 (40%) of patients would prefer to discuss ADs with their oncologist, and 40% with their primary care doctor. 86% would discuss ADs with the admitting doctor. There was no difference in doctor preference based upon prior AD completion. The preference not to discuss ADs with the oncologist was often because they felt their family could make the decisions, or that it was only necessary “If it got serious.” There was a common misconception that ADs mean death is imminent and lead to termination of care. Conclusions: Most patients (86%) are willing to discuss ADs with an admitting doctor, but only a small number (22%) want to discuss with their ONC. However, most patients will discuss ADs and 40% actually prefer their ONC if ADs are discussed. We therefore need to train primary care doctors, house staff, hospitalists, and oncologists to have these difficult discussions. [Table: see text] No significant financial relationships to disclose.
Genetic variation in immunomodulatory genes as markers of melanoma recurrence-free and overall survival.
Authors: Justin Rendleman, Shulian Shang, Jerry Shields, Christina Adaniel, Nathaniel H. Fleming, Richard Shapiro, Russell S. Berman, Anna C. Pavlick, Yongzhao Shao, Iman Osman, Tomas Kirchhoff
Journal: Journal of Clinical Oncology (2013)

9021 Background: Small reported studies have provided some evidence implicating immune related genes in melanoma susceptibility and prognosis; however candidate selection of these prior efforts has been limited. In this study, we performed an analysis of germline variants in immuno-modulatory genes for their association with melanoma survival in a well characterized cohort of prospectively accrued melanoma patients. Methods: Germline DNA isolated from blood samples of 817 melanoma patients was genotyped for 94 SNPs tagging 55 immuno-modulatory genes using Sequenom iPLEX. Cox models were used to test associations between each SNP and recurrence-free and overall survival (RFS and OS), with adjustments for age, gender, subtype, thickness, ulceration, and anatomic site. ROC curves were constructed from different SNP/clinical covariate combinations and the area under the curve (AUC) was used to assess their utility in the classification of 3-year recurrence. Results: The SNP rs2796817 in TGFB2 had strong associations with both RFS (HR=3.8, CI 95%: 1.3-11, p=0.02) and OS (HR=5.5, CI 95%: 1.6-19, p=0.029). Other interesting associations with OS came from IRF8 (rs4843861, HR=0.62, CI 95%: 0.39-0.99, p=0.017), CCL5 (rs4796120, HR=7.6, CI 95%: 2.3-25, p=0.035), and CD8A (rs3810831, HR=2.4, CI 95%: 0.91-6.2, p=0.048). A multivariate model including stage, subtype, and one of the SNPs (rs3810831 from CD8A), was shown to improve the AUC when compared to a model including only stage and subtype (0.77 vs. 0.79). Conclusions: We identified several immune-related loci associated with melanoma RFS and OS. The strongest association, rs2796817, maps in TGFB2, which among other functions suppresses IL-2 dependent T-cell growth. In addition to other associations found in the study these findings provide evidence for the involvement of immuno-modulatory genes in melanoma prognosis and suggest further investigations of immune related genes in disease progression. This is currently underway in the second stage validation analysis, which includes an expanded set of immune target genes as well as an additional independent cohort of melanoma patients.
Frequency of actionable genomic alterations in early-stage lung adenocarcinoma (LA) detected by next-generation sequencing (NGS).
Authors: Kai Wang, Philip Stephens, Roman Yelensky, Jeffrey S. Ross, Vincent A. Miller, Nicholas J Dracopoli, Maureen T. Cronin, Suso J. Platero
Journal: Journal of Clinical Oncology (2012)

e17541 Background: Early stage LA (≤T1N0) has a variable natural history. Although many patients are cured (~2/3) with surgery, many tumors recur and better methods are needed to distinguish these subsets and tailor therapy accordingly. We undertook a pilot study of NGS in such tumors to characterize the frequency and diversity of actionable genomic alterations in this setting. Methods: Formalin-fixed paraffin embedded (FFPE) tissues from 21 archival samples collected from 2007 to 2011 were obtained commercially with accompanying clinical and pathologic data. Clinical characteristics: female (17)/male (4); T1N0 (18), AIS (2), MIA (1). Pathologic LA subtype: acinar (n=8), mucinous (n=4), lepidic (n=4), and mixed (n=2) in addition to AIS (n=2) and MIA (n=1). Targeted NGS performed in a CLIA laboratory (Foundation Medicine) gave evaluable results in all cases. Genomic libraries were captured for 3230 exons in 182 cancer-related genes plus 37 introns from 14 genes often rearranged in cancer and sequenced to average median depth of 640X with 99% of bases covered &gt;100X. Results: Forty-one driver mutations were identified in 17 genes among the 21 patients (avg= 1.9) including 28 base substitutions, 5 indels, 4 amplifications, 3 homozygous deletions and 1 rearrangement. Notably, 90% of cases (19/21) harbored at least one alteration that can be classified as actionable-linked to an approved therapy in LA or another tumor type or a clinical trial. Examples include alterations in EGFR (n=6), NF1 (n=2, PI3K/mTOR inhibitors), CDNK2A (n=1, CDK inhibitors), EML4-ALK (fusion, n=1, ALK inhibitor), ERBB2 (n=1, TKI inhibitors), STK11 (n=1, mTOR inhibitors), and MDM2 (n=1, nutlins). Conclusions: NGSidentified drivergenomic alterations in T1N0 LA, MIA and AIS. On average, two known driver mutations were identified per tumor, many of which are associated with existing or emerging targeted therapies. This provides rationale for future investigation of larger series of T1N0 LA, AIS and MIA, using NGS to evaluate the prognostic value of these changes and could presage adjuvant trials in higher risk patients.
Factors and barriers associated with changes in physical activity after cancer diagnosis.
Authors: Sally A. D. Romero, Qing Susan Li, Jun J. Mao
Journal: Journal of Clinical Oncology (2017)

162 Background: Cancer patients experience a variety of symptoms (e.g., pain, fatigue) that can impact their ability to maintain physical activity (PA) levels. The objectives of this study were to examine factors associated with decreased levels of PA following cancer diagnosis and to identify barriers to PA. Methods: We recruited cancer patients from one urban academic medical center and 11 affiliated community hospitals to participate in a cross-sectional study. We conducted chi-square tests and multivariate logistic regression models to examine patient demographics, clinical characteristics and self-reported barriers associated with decrease in PA levels since cancer diagnosis. Results: Among 662 participants, mean age (SD) was 59.9 (11.6) years. The majority were female (65%), White (81%), and overweight/obese (65%). Common cancer types were breast (32%), lung/thoracic (15%), and hematological (15%), 53% had non-metastatic disease, and 53% were &gt; 12 months post-cancer diagnosis. The majority received chemotherapy (88%), radiation (53%), and/or surgery (53%). Since their cancer diagnosis, 499 (75%) participants reported decreasing their PA levels, 16% maintained, and 4% increased their PA levels. In multivariate analyses, decreased PA levels were significantly associated with receiving chemotherapy [Adjusted Odds Ratio (AOR) 3.54, 95% CI 2.06-6.06] and having metastatic disease (AOR 1.64, 95% CI 1.07-2.52). For barriers to PA, the most common were fatigue (78%), pain (71%), difficulty getting motivated (68%) and difficulty remaining disciplined (65%). In bivariate analyses, the presence of symptoms (i.e., pain, nausea, fatigue, treatment side effects, or surgical complications), difficulty getting motivated, difficulty remaining disciplined, and sadness were significantly associated (p &lt; 0.05) with decreasing PA levels. Conclusions: The majority of cancer patients, especially those who received chemotherapy and those with advanced disease, decreased their PA levels since cancer diagnosis. In addition, physical and psychological barriers exist that influence PA levels. Interventions targeting these barriers are needed to promote maintenance of PA levels throughout the cancer continuum.
Clinical efficacy of sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma.
Authors: Xu Zhang, Jianlin Yuan, Liang Wang, Lijun Chen, Jinhong Pan, Linyang Ye, Xuren Xiao, Jianhong Qiu, Keqin Zhang, Gang Ye
Journal: Journal of Clinical Oncology (2013)

e15547 Background: To evaluate the efficacy and safety of Sunitinib as post-operative adjuvant therapy in patients with high-risk renal cell carcinoma (RCC). Methods: A total of 60 patients with resected, histologically confirmed clear cell RCC were enrolled in this study. Patients received orally Sunitinib either at a dose of 50mg on treatment schedule 4/2 (once daily for 4 weeks followed by 2 weeks off) or at a dose of 37.5mg once daily for three 6-week cycles from 1 month after surgery. Results: All 60 patients tolerated Sunitinib treatment well and no patient discontinued treatment due to adverse events. Most adverse events were grade 1 to 2. The most frequently reported adverse events were neutropenia (56.7%), thrombocytopenia (53.3%), leucopenia (48.3%), hand-foot syndrome (46.7%) and hypertension (36.7%). The most frequently reported grade 3 or 4 toxicities were thrombocytopenia (25%), neutropenia (15%), hand-foot syndrome (11.7%) and leucopenia (8.3%). The majority of adverse events occurred within the first 1-2 cycles of Sunitinib treatment, and was ameliorated 1 month after 3 cycles finished. No irreversible adverse event was observed. As of January 31, 2013, recurrence occurred in 3 of 60 (5%) patients except one death due to cerebrovascular accident unrelated to treatment, with 12-month disease-free survival (DFS) rate of 96.6% (RCC recurred 7 months after surgery in 2 patients and recurred 14 months after surgery in 1 patient). Conclusions: Myelosuppression occurred less frequently in high-risk RCC patients treated with Sunitinib as operative adjuvant therapy than in advanced RCC patients, with a better benefit trend. Long-term follow-up data are needed to further confirm the efficacy of Sunitinib in the adjuvant setting.
Influence of metformin use on the transformation of monoclonal gammopathy of undetermined significance into multiple myeloma.
Authors: Su-Hsin Chang, Suhong Luo, Katiuscia O'Brian, Theodore S. Thomas, Graham A. Colditz, Kenneth Robert Carson
Journal: Journal of Clinical Oncology (2014)

1532 Background: Multiple myeloma (MM) is the second most common hematologic malignancy in the United States and is preceded by monoclonal gammopathy of undetermined significance (MGUS). Stimulation of the insulin-like growth factor receptor pathway is a hypothesized mechanism for the progression of MGUS to MM; therefore, alteration of this pathway with metformin could reduce the risk of progression. We evaluated the influence of metformin use on the transformation of MGUS to MM in a retrospective cohort. Methods: Patients with MGUS and diabetes mellitus diagnosed between 1998 and 2009 were identified in the U.S. Veterans Health Administration (VHA) database. Unique identifiers were used to link data to the pharmacy database to obtain diabetes medications. Two investigators reviewed patient-level clinical information to verify dates of MGUS and MM diagnoses, and abstract additional data, including size of baseline M protein, immunoglobulin (Ig) subtype, and serum-free light-chain ratio, when available. The duration of metformin use was determined by the dates of the first and last prescription before 2013 or MM diagnosis. Several threshold values for dichotomization around the median duration of metformin use for patients developing MM were examined. Cox proportional hazard models, adjusting for age, body mass index, race, sex, Ig subtype, and size of M spike, were used to analyze the association between metformin use and the time from MGUS diagnosis to MM diagnosis. Results: 2,116 MGUS patients with diabetes were identified after excluding those with IgM MGUS. Among them, 38% were not treated metformin and 113 patients developed MM. We found that metformin use over 46 months (median duration of metformin use for MM patients) was protective, but not statistically significant (HR: 0.83; 95% CI: 0.55-1.24). However, metformin use over 4.5 years (54 months) was significantly protective with HR: 0.60 and 95% CI: 0.38-0.94. Patients with M protein concentration ≥1.5 g/dL (HR: 6.32; 95% CI: 3.7-10.8) and IgA monoclonal protein (HR: 1.82; 95% CI: 1.15-1.90) had a higher risk of progression. Conclusions: Prolonged metformin use was associated with a reduced risk of transformation from MGUS to MM.
Awareness and understanding of cancer immunotherapy in Europe.
Authors: Hakan Mellstedt, Gustav Gaudernack, Winald R. Gerritsen, Christoph Huber, Ignacio Melero, Giorgio Parmiani, Suzy Scholl, Nick Thatcher, John Wagstaff, Christoph Zielinski
Journal: Journal of Clinical Oncology (2013)

3053 Background: Use of immunotherapies in the treatment of cancer is growing and a range of new immunotherapeutic strategies are being evaluated. It is important that healthcare providers (HCP) understand these treatments and how they compare with and may complement established therapies. As part of the activities of the POINT expert group, we commissioned a survey of current awareness, attitudes and perceptions of cancer immunotherapy in Europe. Methods: From August-September 2011, 426 healthcare professionals (HCPs: oncologists, surgeons and oncology nurses) from France, Germany, Italy, Spain and the UK (~85 respondents/country) completed online interviews. Representatives of patient advocacy groups (PAGs) in each country were surveyed by telephone interview. Results: Nearly all (98%) HCPs were aware of cancer immunotherapy. While 68% of HCPs indicated a high level of interest, knowledge levels were lower. Only 24% of the HCPs had direct experience with cancer immunotherapies, while others reported they knew a lot (12%), a reasonable amount (28%) or little (34%) about immunotherapy strategies but had not used them (76%). Overall perceptions of cancer immunotherapy among HCPs were largely positive (60%) and rarely negative (3%). The key advantages of cancer immunotherapy were perceived to be good safety and tolerability (75%), a targeted mechanism of action (61%) and good efficacy (48%). The leading barriers to use of immunotherapies were costs of treatment (58%), past clinical trial failures (45%) and access/formulary restrictions (44%). Most (75%) HCPs had already discussed cancer immunotherapy with their patients and 70% of patients were reported as being receptive to the concept. The majority of PAGs indicated they were currently unable to advise patients about cancer immunotherapy due to a lack of or confusing information and poor understanding. Conclusions: Awareness of cancer immunotherapy in Europe is high and it is generally perceived as a positive addition to established treatment options. However, the understanding varies and the direct experience is limited. There is a clear need for further educational activities concerning cancer immunotherapy, as well as further clinical data on long-term efficacy and safety.
Diagnostic characteristics of men harboring lethal prostate cancer: A population-based analysis.
Authors: John Thomas Helgstrand, Nina Klemann, Birgitte Grønkaer Toft, Ben Vainer, Klaus Brasso, Peter Iversen, Martin Andreas Røder
Journal: Journal of Clinical Oncology (2017)

217 Background: Prostate specific antigen (PSA) based screening increases the number of men diagnosed with early localized prostate cancer (PCa). Further, curatively intended therapies have been demonstrated to reduce PCa mortality in randomized trials. However, controversy exists, and the overall impact on PCa mortality is less clear. Men who eventually die from PCa may constitute a subgroup with either adverse histopathological characteristics and/or clinically advanced disease at diagnosis. However, the clinical characteristics at diagnosis for men who eventually die from PCa are largely unknown. We retrieved clinical characteristics of all men dying from PCa in Denmark in an 18-year period. Methods: All men who died of PCa during the period 1995 to 2013 were identified in the Danish Causes of Death Registry. Age, Gleason score (GS), tumor stage classification, and PSA were retrieved from the Danish Prostate Cancer Registry (DaPCaR). For validation, manual revision of patient charts was performed. Patients were divided into three clinical phenotypes: distant metastatic disease, locally advanced/N+ disease, and localized disease. Patients with localized disease were further grouped according to GS and PSA. Results: A total of 19,487 men died of PCa in the period 1995-2013. In total, 46.7%, 16.8% and 25.1% of men presented with distant metastatic disease, locally advanced/N+ disease or localized disease, respectively. Among men with localized disease, 85.1% had GS ≥ 7 and only 2.1% (0.5% of all men dying from PCa) only, presented with low risk (PSA &lt; 20 and GS ≤ 6) localized disease at the time of diagnosis. Conclusions: The majority of men (63.5%) who died from PCa had either locally advanced/N+ or M+ disease at diagnosis. Among men with localized PCa at diagnosis, the majority of men subsequently dying from PCa had either PSA &gt; 20 ng/ml and/or adverse histopathological characteristics with Gleason score ≥ 7. A total of 94.5% of patients dying from PCa had either metastatic, locally advanced/N+, and/or GS ≥ 7 disease. Patients with localized disease, PSA &lt; 20 ng/ml and GS ≤ 6 amounted for only 0.5% of all patients dying from PCa.