tbuckley/cabot-search huggingface dataset:
Analysis of outcomes in metastatic pancreatic cancer: Real-world experience in academic cancer centers.
Authors: Elizabeta C. Popa, Emma Rabinovich, Davendra Sohal, Kathryn Cecilia Arbour, Timothy Suyong Kim, Yao Lu, Paul J. Christos, Alok A. Khorana, Manish A. Shah
Journal: Journal of Clinical Oncology (2017)

458 Background: FOLFIRINOX is an active regimen for metastatic pancreatic cancer demonstrating a median overall survival of 11.1 months at the expense of significant treatment-related toxicity. Dose modifications are routinely used in clinical practice however there is little data regarding impact on outcomes and use of second line therapy. In this study we report on the treatment course and outcomes of 92 patients treated at two academic centers. Methods: We conducted an IRB-approved retrospective cohort study of patients with metastatic pancreatic adenocarcinoma treated with first line FOLFIRINOX between 2011 and 2015. Hazard ratios were calculated by Cox proportional hazard models and median survival was estimated using Kaplan-Meier method. Results: 92 patients were identified with a median follow-up of 13.2 months (range 1.2-47.3 mo); 57 males (62%), ECOG 0/1 = 75 (82%). Fifty-four percent required dose reductions of &gt;25% in at least one of three component drugs within the first 6 cycles [95% CI 0.44, 0.65]. Irinotecan was dose reduced in 43% of patients (n=39) while 64% required modification or discontinuation of 5FU. Ten patients (11%) received the full dose of FOLFIRINOX as originally published and 17 patients (25%) discontinued FOLFIRINOX due to toxicity. 60% of patients demonstrated disease control at first imaging assessment after 4-6 cycles of treatment. Median PFS was 7.11 months (95% CI: 5.06-8.51) and OS 13.01 months (95% CI: 9.17-16.95). There was a decrease in PFS and OS associated with a dose reduction of two or more drugs with a HR of 1.68 (95% CI 1.01-2.82, p=0.048) and 1.98 (95% CI 1.08-3.65, p=0.027) respectively. Sixty-seven patients [73%] went on to receive 2 nd line therapy [n=67] with 55% receiving gemcitabine-based regimens, the majority with nab-paclitaxel [82%]. Forty-two patients demonstrated progressive disease [63%]. Conclusions: Modest FOLFIRINOX dose modifications are prevalent in clinical practice and are not associated with a reduction in efficacy. A median survival of 13 months with dose modified FOLFIRINOX is compelling. Dose reduction of 2 or more agents was associated with diminished survival. Second line therapy following FOLFIRINOX was associated with modest activity.
Accuracy and usefulness of a clinical prediction rule and D-dimer testing in excluding deep vein thrombosis (DVT) in cancer patients
Authors: M. Carrier, A. Lee, S. Bates, P. S. Wells
Journal: Journal of Clinical Oncology (2007)

19522 Background: Cancer patients frequently present with thrombotic complications and rapid, accurate diagnostic testing would reduce morbidity and mortality. Although the combination of a low clinical probability using clinical prediction rules (e.g. Well’s Score) and a negative D-dimer result have proven to be safe and reliable in ruling out DVT in the general population, the accuracy of such a strategy is less certain in cancer patients. Because cancer patients often have alternative reasons for leg swelling and pain, and because malignancy and chemotherapy can render the D-dimer test positive in the absence of DVT, we hypothesize that the Well’s Score and D-dimer testing are potentially less accurate and less useful in excluding DVT in patients with active cancer. Methods: We performed a retrospective analysis of 2 prospective studies to compare the diagnostic test characteristics of the Well’s Score and D-dimer testing between patients with and without cancer presenting with suspected DVT. Results: A total of 1630 patients were studied; 107 had cancer. DVT was confirmed in 39.3% of patients with and 13.7% of patients without cancer. In both patient groups, the proportions of patients with DVT were significantly different among the high-, moderate- and low-probability groups according to the Well’s score (P&lt;0.001). However, significantly fewer cancer patients (19.6%) had a low-probability score compared to patients without cancer (47.5%) (P&lt;0.001). Similarly, 36.4% of cancer vs. 60.4% of noncancer patients had a negative D-dimer result (P&lt;0.001). In cancer patients, a low probability score alone had a sensitivity of 95.2% (95%CI 82.6%-99.2%) and a specificity of 29.2% (95% CI 18.9%-42.0%). In combination with D-dimer testing, the sensitivity improved to 100% (95%CI 31.0%-100%) but the specificity was reduced to 26.4% (95%CI 13.5%-44.7%). In contrast, the specificity in patients without cancer was preserved at 53.9% (95%CI 50.4%-57.3%). Conclusion: DVT can be ruled out in cancer patients with a low clinical probability of DVT and a negative D-dimer result. However, the low specificity of these tests excludes very few patients and thereby limits their clinical usefulness. No significant financial relationships to disclose.
Integrated oncopalliative care versus standard care for patients with metastatic lung cancer: A single institution retrospective review.
Authors: Jonathan Douglas King, Janet Retseck, Jens C. Eickhoff, Tien Hoang, Anne M. Traynor, Toby Christopher Campbell
Journal: Journal of Clinical Oncology (2013)

9566 Background: Patients with metastatic non-small cell lung cancer (NSCLC) receiving early palliative care (PC) demonstrated improved anxiety, quality of life, and survival compared to standard oncology care (SOC). ASCO clinical practice guidelines recommend concurrent PC and SC be offered to patients with metastatic NSCLC. Our lung cancer clinic is partially integrated with PC. We performed retrospective chart review comparing patients seen in our integrated clinic with SOC patients for survival, trial participation, chemotherapy and hospice utilization. Methods: Charts of all patients with advanced lung cancer from July 2007-June 2011 were reviewed. Eligible patients were those who received any care at our center. Demographic, treatment details, survival, and hospice utilization data were obtained. Overall survival and length of hospice enrollment were calculated for patients treated with PC compared to SOC. Results: Of 207 patients, 82 received PC. Overall survival favored PC (11.9 months vs. 10.1 months, p=0.032). Hospice length of stay (LOS) favored PC (38.5 days vs. 24 days in SOC, p=0.047). There was not a significant difference in lines of chemotherapy, chemotherapy in the last 30 days of life, or trial participation. Conclusions: Our chart review provides confirmatory evidence that early integrated PC in lung cancer patients increases survival and hospice LOS without affecting chemotherapy utilization or trial participation. [Table: see text]
Lymph node yield and survival in gastric carcinoma.
Authors: Jennifer E. Samples, Karyn Beth Stitzenberg, Michael O. Meyers
Journal: Journal of Clinical Oncology (2014)

4012 Background: Although the extent of lymph node (LN) dissection in gastric cancer remains controversial, it is recommended that at least15 LN be examined for accurate staging. Existing data suggest that many gastrectomies performed in the US do not achieve this benchmark. This study examines trends in LN yield over time in patients undergoing curative surgery for gastric cancer and the relationship between LN yield and survival. Methods: Under IRB waiver, all National Cancer Database patients who underwent total, distal or proximal gastrectomy for gastric cancer from 1998-2011 were examined. Patients with metastatic disease or for whom treatment was indicated to be palliative were excluded from this study. Wilcoxan rank-sum test was used to compare LN yield. Cox proportional hazards models were used to compare overall survival. Results: 73,674 patients met inclusion criteria. 7,938 (10.8%) had neoadjuvant therapy. Patients who received neoadjuvant therapy had higher median LN yield than patients who did not (12 vs. 9, p<0.001). Median LN yield improved over time (8 in 1998 vs. 11 in 2011, p<0.001), as did the proportion of patients with LN yield >15 (21% in 1998 vs. 36% in 2011, p<0.001). Median overall survival (OS) was positively associated with LN yield in node-positive and node-negative patients. See Table. These survival differences persisted after adjustment for patient demographics and comorbidity. Conclusions: Slow improvement in LN yield has been seen on a population level over the past two decades, although nearly two thirds of all patients undergoing curative resection still have fewer than 15 LN examined. Higher LN yield is associated with better OS in patients with resectable gastric carcinoma. Based on these results, continued effort is needed to improve surgical quality in patients undergoing curative resection for gastric cancer. n 0-15 LN 16-25 LN 26+ LN 0-15 LN (ref) 16-25 LN 26+ LN Median survival (months) aHR aHR CI aHR CI T1-2N0 21079 75 109 121 1.0 0.75 0.67-0.81 0.71 0.63-0.81 T-2N1 11283 29 43 67 1.0 0.83 0.77-0.89 0.63 0.57-0.71 T3N0 5814 31 56 69 1.0 0.73 0.64-0.82 0.65 0.53-0.79 T3N1 10462 17 26 37 1.0 0.79 0.74-0.85 0.59 0.53-0.66 T1-2N2-3 3305 17 22 37 1.0 0.77 0.69-0.86 0.51 0.43-0.60 T3N2-3 6176 12 16 19 1.0 0.75 0.69-0.81 0.66 0.59-0.74
Association of inherited genetic variation with clinical outcome in patients with advanced renal cell carcinoma treated with mTOR inhibition.
Authors: Mark M Pomerantz, Kathryn P. Gray, Fabio Augusto Barros Schutz, Andrew Percy, Megan Lampron, Sabina Signoretti, Michelle S. Hirsch, Jonathan E. Rosenberg, Gwo-Shu Mary Lee, David F. McDermott, Michael B. Atkins, Philip W. Kantoff, Matthew L Freedman, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2012)

4543 Background: Mammalian target of rapamycin (mTOR)-targeted therapy is standard in patients with metastatic renal cell carcinoma (mRCC). Predictive biomarkers for response are lacking. We sought to characterize outcome after mTOR inhibition based on germline variation in 2 critical genes in the mTOR pathway: phosphoinositide-3-kinase catalytic alpha (PIK3CA) and mTOR. Methods: 76 Americans of European ancestry treated with temsirolimus or everolimus for mRCC were included. Germline DNA was genotyped for all common genetic variation (minor allele frequency [MAF] &gt;0.05) across PIK3CA and mTOR, tagging with single nucleotide polymorphisms (SNPs) at r 2 &gt;0.8. Associations between genotype and progression-free survival (PFS) and overall survival (OS) from the start of mTOR-targeted therapy were measured using univariate Cox model. Results: Among 76 patients, 66% were poor or intermediate risk and 89% received prior systemic therapies. Median follow up was 23.7 months. Median PFS and OS were 4.3 and 12.7 months, respectively. Two intronic PI3KCA SNPs were significantly associated with PFS and OS, and a SNP in the 5’ UTR of mTOR was associated with OS. Associations were maintained when adjusted for age, gender and MSKCC RCC risk categories using Cox PH model (Table). The PI3KCA SNPs are in modest linkage disequilibrium (r 2 ~0.36). Conclusions: We suggest that inherited variation at PIK3CA is associated with PFS and OS after mTOR inhibition. If results are validated, prospective studies could explore the role of genotyping in treatment selection for mRCC. Further work will be needed to identify causal alleles and define the mechanism underlying the associations. [Table: see text]
m 6 A Demethylase ALKBH5 Maintains Tumorigenicity of Glioblastoma Stem-like Cells by Sustaining FOXM1 Expression and Cell Proliferation Program
Authors: Sicong Zhang, Boxuan Simen Zhao, Aidong Zhou, Kangyu Lin, Shaoping Zheng, Zhike Lu, Yaohui Chen, Erik P. Sulman, Keping Xie, Oliver Bögler, Sadhan Majumder, Chuan He, Suyun Huang
Journal: Cancer Cell (2017)
Less toxic chemotherapy on the uptake of all lines of chemotherapy in advanced non-small cell lung cancer: A 10-year retrospective population-based review.
Authors: Cheryl Ho, Katherine Ramsden, Nevin Murray, Sophie Sun, Barbara L. Melosky, Janessa J. Laskin
Journal: Journal of Clinical Oncology (2013)

e19131 Background: The platinum doublet is standard first-line therapy in advanced NSCLC. Over the past decade, well-tolerated second-line therapies have been approved, including erlotinib and pemetrexed. We hypothesize that the introduction of less-toxic chemotherapy has increased treatment of advanced NSCLC, resulting in improved survival. Methods: The BC Cancer Agency provides cancer care to a population of 4.5 million. A retrospective review was conducted of all referred stage IIIB/IV patients in four 1-yr time cohorts; C1 baseline (1998) and 6 months after the provincial approval of C2 docetaxel (2001), C3 erlotinib (2006) and C4 pemetrexed (2007). Results: 2,623 patients were referred and 720 had systemic therapy. Characteristics: M/F 55%/45%, median age 67 (33-101), ECOG &lt;=1/&gt;=2/unknown 33%/56%/11%, never/former/current/unknown smoker 9%/35%/36%/20%, squam/nonsquam/NOS 18%/41%/41%. More patients received first-line chemotherapy over time; 16%, 23%, 34%, 33% C1-4 respectively. In C1 to C4 uptake of second line (21%, 27%, 38%, 55%) and third line (10%, 10% 14%, 18%) increased. In C1 the most common first-line doublet was cis/vino (70%) and in C4, cis/gem (45%). Second-line doce was frequently used in C2 (51%) but usage decreased in C4 to 7% vs. erlo 50% and pem 26%. In the &gt;=70 group (n=1,118), first-line usage increased from C1 9% to C4 19% and second-line in the C2 (doce) 4% to C4 (erlo+pem avail) 56%. The increased use of systemic therapy was associated with improved survival in all patients: C1 4.56 m vs C4 4.98 m (p=0.004) and treated patients; C1 9.48 m vs C4 12.07 m (p=0.014) and the &gt;= 70 group; C1 9.7 m vs C4 12.5 m (p=0.07). Conclusions: This population-based data set represents the trend of treatments over time in a large geographical area, including community and tertiary care cancer treatment sites. The introduction of less-toxic systemic therapy for advanced NSCLC resulted in an increased proportion of patients treated with first-line chemotherapy and an even greater increase in second-/third-line treatment. This trend was particularly evident in the elderly. Associated with this was a significant improvement in overall survival for all subsets.
Targeting Ikkα in CLL: Inhibition of Non-Canonical NF-κb Signaling Decreases Survival and Proliferation of CD40L-Stimulated Primary CLL Cells
Authors: Elaine Willmore, Aaron Gardner, Susan J Tudhope, Andrew Herridge, Jill Hunter, Jonathan P Wallis, Helen J Marr, Giacomo Berretta, David Breen, Andrew Paul, Darren Edwards, Louise C Young, Colin J Suckling, Robin Plevin, Marie Boyd, James M Allan, Simon Mackay, Neil D Perkins
Journal: Blood (2016)
A single-institution experience with the pembrolizumab (PEM) Expanded Access Program (EAP).
Authors: Karen Mae Perdon, Dae Won Kim, Gener C Balmes, VanAnh Trinh, Susan E McIntyre, Adi Diab, Rodabe Navroze Amaria, Sapna Pradyuman Patel, Patrick Hwu, Marihella James, Ann Philip, Anna Vardeleon, Suzanne Cain, Wen-Jen Hwu
Journal: Journal of Clinical Oncology (2015)

e20088 Background: PEM is contingently approved in the US to treat patients (pts) with advanced melanoma (MEL) whose disease progressed following ipilimumab (IPI) and a BRAF inhibitor (if BRAFV600-mutated MEL). We report our clinical experience of MEL pts enrolled in the PEM EAP. Methods: 62 pts were enrolled and treated on PEM EAP from May to September 2014 at MD Anderson Cancer Center. PEM was administered at 2 mg/kg every 3 wk until unacceptable toxicity, disease progression, or for up to 2 yr. Toxicity was assessed before each dosing. Response was evaluated every 12 wk (after every 4 doses) using immune-related response criteria. Results: Table showsbaseline characteristics of 60 pts included in the efficacy analysis (excluding 2 pts with uveal MEL). Median number of PEM doses administered was 6 (range 1-12). At a median follow-up of 5.4 mo (range 0.2-7.8), the overall response rate (ORR) was 22% (26% in 51 pts who received ≥ 4 doses), with 17% (20%) stable disease. Median progression-free survival (PFS) was 3.5 mo (95% CI 2.8-4.8); median overall survival (OS) was not reached (95% CI 6.7-not evaluable). Univariate analysis showed a statistically significant association between OS and ECOG PS and LDH; PFS and ORR were associated with ECOG PS, LDH, and stage. BRAF mutation status was not associated with treatment outcome. Adverse drug events (ADE) occurred in 87% of pts (n = 62), all grade 1/2. ADE of interest were pruritus (11%), rash (18%), diarrhea (18%), elevated liver function tests (42%) and abnormal thyroid function tests (9.6%). One pt developed grade 2 pneumonitis. Grade 3-4 toxicities and treatment-related deaths were not observed. Conclusions: Our experience with PEM EAP was similar to published data of PEM in metastatic MEL. PEM is safe and effective in pts with advanced MEL refractory to standard-of-care therapy including IPI and BRAF inhibitor. Clinical trial information: NCT02083484.Patient characteristics. Number of patients N Age Median (Range) Stage M1c N (%) Prior Therapies Median (Range) Elevated LDH N (%) History of Brain Metastases N (%) Mutations N (%) ECOG PS N (%) BRAF NRAS 0 1 60 60.5 (16-85) 45 (75) 2 (1-7) 25 (42) 15 (25) 15 (25) 20 (33.3) 40 (66.7) 20 (33.3)
Surveillance for respiratory infectious diseases caused by 6 common viruses in a recruit training site in the Northern region of China
Authors: Wei-Wei Chen, Wen Xu, Yang-Xin Xie, Yun-Hui Zhang, Dan Wu, Fu-Sheng Wang, Min Zhao
Journal: Military Medical Research (2017)

Recruit training sites are places with a high incidence of respiratory infectious diseases. Effective surveillance for acute respiratory infectious diseases in a recruit training site is an important way to prevent disease outbreaks.Eight hundred recruits (722 males and 78 females) enlisted in autumn 2015 received a background survey within 24 h of settlement at the recruit training site, including their general personal information, vaccination history, mental status and clinical symptoms. Then, nasopharyngeal swabs of these recruits were collected to detect common respiratory pathogens [influenza virus type A, influenza virus type B, adenovirus (Adv), human respiratory syncytial virus, human bocavirus and human metapneumovirus] by PCR. In addition, fasting venous blood was collected in the morning for adenovirus IgG antibody detection. During the three months of training, the recruits were monitored for symptoms of respiratory infection, and nasopharyngeal swabs were collected from those with an axillary temperature ≥38 °C and other respiratory symptoms within 4 h of symptom onset. Samples were further examined by PCR.Among the 795 effective nasopharyngeal swab samples collected during survey, two cases of group C type 1 adenovirus were identified by PCR. During the 3 months of training, fever and respiratory symptoms occurred in 39 recruits (incidence rate of 4.9%) and 5 cases of adenovirus were detected (positive rate of 12.8%). Genotyping showed 3 cases of type 4 adenovirus and 2 of type 3 adenovirus. No type 7, 14 or 55 adenovirus was detected. The Adv-IgG positive rate of recruits was 48.2%. Among the 5 Adv positive cases with fever and respiratory symptoms, 4 were Adv-IgG positive.The pathogen carrier rate in recruits was low, and only group C adenovirus, which causes mild infection in humans, was detected. No respiratory outbreak was observed at the recruit training site, and sporadic cases were mainly caused by type 3 and type 4 adenoviruses.
Impact of care at NCI Comprehensive Cancer Centers (NCICCC) and payor status on outcomes in osteosarcoma (OS), Ewing sarcoma (ES) and rhabdomyosarcoma (RMS).
Authors: Julie Anna Wolfson, Can-Lan Sun, Laura Wyatt, Smita Bhatia
Journal: Journal of Clinical Oncology (2015)

e17537 Background: Effective management of ES/OS/RMS requires a multidisciplinary approach. Whether care at specialized centers (e.g., NCICCCs) affords a survival advantage across socioeconomic strata remains unstudied. Methods: We constructed a population-based cohort of 629 patients with newly diagnosed (dxed) ES/OS/RMS reported to Los Angeles cancer registry between 1998 and 2008. Multivariable Cox regression was used to determine impact of care at NCI sites (NCICCCs [all ages]; Children’s Oncology Group [COG] sites [<21y]) on overall survival adjusting for dx, stage, age, SES, payor. Logistic regression was used to determine likelihood of care at NCI sites, adjusting for above variables and distance to nearest center (using GIS). Results: Clinical characteristics in Table.Median age at dx was 17y (0-65y). Survival: Multivariable analysis revealed payor as a risk factor for survival (uninsured: HR=1.7, 95%CI 1.0-2.8, p=0.04; ref: private insurance). A significant NCI/payor interaction (p=0.01) was observed. Payor status did not impact outcome at NCI sites. Compared to privately insured community patients, publicly insured (HR=1.5, 95%CI 1.1-2.1, p=0.02) and uninsured (HR=2.0, 95%CI 1.1-3.6, p=0.03) community patients saw poor outcome. Finally, publicly insured patients fared poorly in community vs. NCI sites (HR=1.5, 95%CI 1.1-2.1, p=0.02). Access to care: <21y olds: lower likelihood of care at NCI sites was seen in 15-21y (OR=0.4, 95%CI 0.2-0.6, p<0.001), patients >7 miles from NCI site (OR=0.6, 95%CI 0.4-1.0, p=0.04) and low SES (OR=0.4, 95%CI 0.2-0.7, p<0.01). >22y olds were less likely to receive NCI care if publicly insured (OR=0.2, 95%CI 0.04=0.8, p=0.02), low SES (OR=0.4, 95%CI 0.2-0.9, p=0.02) or non-White races/ethnicities (OR=0.3, 95%CI 0.1-0.7, p<0.01). Conclusions: At community sites, lack of private insurance predicts poor survival. Care at NCI sites mitigates poor outcome in the publicly insured. Barriers to care at NCI sites differ by age and could inform intervention strategies. Cohort characteristics. n ;% ES 185; 29% OS 306; 49% RMS 138; 22% Non-Hispanic white 199; 32% Low SES 296; 47% Privately insured 393; 63% Care at NCI 252; 40%