tbuckley/cabot-search huggingface dataset:
Center impact on survival in metastatic colorectal cancer trials.
Authors: H. Marijon, B. Chibaudel, F. Bonnetain, C. Tournigand, L. Teixeira, L. Bengrine-Lefèvre, O. Bourges, C. Louvet, A. De Gramont
Journal: Journal of Clinical Oncology (2011)

e14062 Background: Surgeon-volume and hospital-volume influence morbidity and mortality in patients undergoing surgery for cancer, but data are missing concerning influence of chemotherapy (CT) center on outcome in patients treated with CT. The aim of the present study was to evaluate the center effect on survival in patients treated with CT for metastatic colorectal cancer. Methods: Individual patient data from 3 randomized trials evaluating first-line CT in patients with metastatic colorectal cancer were pooled. Patients were separated in different groups according to each center’s volume of inclusion. Baseline characteristics, overall survival (OS), progression-free survival (PFS), response rates, second-line chemotherapy and rate of surgery of metastasis were analyzed. Results: Between 1998 and 2006, 1042 patients were enrolled in 70 centers from 6 countries. Four groups were created (Table). Median OS in groups A and D were 19.3/24.5 months, respectively (HR=1.39 [95% CI: 1.13-1.70], P=.003). There was no difference between the four groups concerning PFS (P=.70), response rates (P=.20) and administration of second-line CT (P=.10). However, oxaliplatin reintroduction and surgery of metastasis were more often performed in group D than in the other groups (P<.001). Conclusions: These data suggest that overall survival could be influenced by center. This could be partly explained by specific therapeutics strategies such as treatment reintroduction and surgery of metastasis. Patient distribution. Group A Group B Group C Group D Center inclusion rate (%) <3 [3-7] [7-12.5] ≥12.5 No. of patients 260 246 257 279 No. of centers 52 11 5 2 Overall response rate (%) 59 54 58 63 Oxaliplatin reintroduction (%) 16 24 32 39 Surgery of metastasis (%) 9 14 18 25 Second-line chemotherapy (%) 70 72 63 65 Median PFS (months) 8.4 8.1 8.2 8.7 Median OS (months) 19.3 20.8 19.2 24.5
Analysis of plasma protein biomarkers from the phase 3 CONCUR study of regorafenib in Asian patients with metastatic colorectal cancer (mCRC).
Authors: Michael Teufel, Joachim Kalmus, Mark Daniel Rutstein, Karl Koechert, Henrik Seidel, Joachim Reischl, Adam Skubala, Richardus Vonk, Scott Wilhelm, Svetlana Kobina, Shukui Qin, Rui-hua Xu, Tae Won Kim, Jin Li
Journal: Journal of Clinical Oncology (2016)

672 Background: In the randomized phase 3 CONCUR trial (NCT01584830), regorafenib significantly improved overall survival (OS) and progression-free survival (PFS) vs placebo (PBO) in Asian patients (n = 136 regorafenib; n = 68 PBO) with treatment-refractory mCRC (HR [95% CI]: OS 0.55 [0.40‒0.77]; PFS 0.31 (0.22‒0.44]). Protein biomarker data from the phase 3 CORRECT trial of mostly Western patients with mCRC identified TIE-1 as a potential predictor of clinical response to regorafenib; however, this association was not significant in multivariable analyses. We present an exploratory protein biomarker analysis of patients in CONCUR. Methods: Sixteen proteins of interest, many of which are involved in angiogenesis, were quantified by multiplex immunoassay or ELISA in plasma samples collected at study entry from 121/204 (59%) patients (n = 83 regorafenib; n = 38 PBO). Potential predictive and prognostic effects were evaluated. Results: The biomarker cohort was representative of the overall study population in major baseline demographic factors, OS (HR 0.61; 95% CI 0.40‒0.93), and PFS (HR 0.25; 95% CI 0.16‒0.39). Elevated levels of ANG-2 (HR 2.46; p = 0.0016) and VEGF-A (HR 1.38; p = 0.03) were associated with poor OS prognosis; however, no significant association with treatment OS benefit for regorafenib vs PBO was observed for either marker (ANG-2: HR 0.76; p = 0.3307; VEGF-A: HR 0.83; p = 0.20). Elevated levels of five plasma proteins were associated with poor PFS prognosis: ANG-2 (HR 1.73; p = 0.0085), VEGF-A (HR 1.30; p = 0.0308), IL-8 (HR 1.67; p = 0.0014), VWF (HR 2.39; p = 0.0029), and IGF-BP2 (HR 1.71; p = 0.0384). Elevated levels of IL-8 (HR 0.70; p = 0.019), VWF (HR 0.53; p = 0.0312), and IGF-BP2 (HR 0.60; p = 0.0336) showed a modest interaction with regorafenib PFS; however, these results did not reach statistical significance after adjustment for multiple testing (p = 0.0045). Conclusions: None of the plasma proteins analyzed were predictive of regorafenib clinical benefit as measured by both OS and PFS in Asian patients with mCRC. These results, as well as those in CORRECT, suggest that rationally selected protein markers are not suitable to predict treatment benefit of regorafenib. Clinical trial information: NCT01584830.
Lipopolyplex potentiates anti-tumor immunity of mRNA-based vaccination
Authors: Stefano Persano, Maria L. Guevara, Zhaoqi Li, Junhua Mai, Mauro Ferrari, Pier Paolo Pompa, Haifa Shen
Journal: Biomaterials (2017)

mRNA-based vaccines have the benefit of triggering robust anti-cancer immunity without the potential danger of genome integration from DNA vaccines or the limitation of antigen selection from peptide vaccines. Yet, a conventional mRNA vaccine comprising of condensed mRNA molecules in a positively charged protein core structure is not effectively internalized by the antigen-presenting cells. It cannot offer sufficient protection for mRNA molecules from degradation by plasma and tissue enzymes either. Here, we have developed a lipopolyplex mRNA vaccine that consists of a poly-(β-amino ester) polymer mRNA core encapsulated into a 1,2-dioleoyl-sn-glycero-3-ethylphosphocholine/1,2-dioleoyl-sn-glycero-3-phosphatidyl-ethanolamine/1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000 (EDOPC/DOPE/DSPE-PEG) lipid shell. This core-shell structured mRNA vaccine enters dendritic cells through macropinocytosis. It displayed intrinsic adjuvant activity by potently stimulating interferon-β and interleukin-12 expression in dendritic cells through Toll-like receptor 7/8 signaling. Dendritic cells treated with the mRNA vaccine displayed enhanced antigen presentation capability. Mice bearing lung metastatic B16-OVA tumors expressing the ovalbumin antigen were treated with the lipopolyplex mRNA, and over 90% reduction of tumor nodules was observed. Collectively, this core-shell structure offers a promising platform for mRNA vaccine development.
Early success in narrowing age, gender, and racial disparities in clinical trial accrual: Targeted screening efforts through the National Cancer Institute Community Cancer Centers Program (NCCCP).
Authors: S. S. Grubbs, R. S. Go, M. Z. Berger, M. Gonzalez, M. A. Thompson, R. Enos, D. C. St. Germain, A. Denicoff, C. Servididio, J. D. Bearden, H. Zaren, K. Wilkinson, M. Krasna, W. McCaskill-Stevens, M. Bell, R. K. Freeman, S. Miesfeldt, T. S. Ravikumar, S. G. Nair, A. Bashey
Journal: Journal of Clinical Oncology (2011)

6110 Background: The NCCCP has engaged in special programs to enhance clinical trial accrual among underserved populations. These include cultural awareness webinars, nurse/lay navigators with translated consent forms and interpreters, expansion of trials in outreach sites, community site pairing, and utilization of a web-based tracking tool to monitor clinical trial screening and accrual barriers. Methods: Screening and accrual data of 19 NCI Cooperative Group trials encompassing 9 disease categories from the geographically diverse NCCCP sites was collected between March 2009 and December 2010. The data included patient demographics, trial eligibility, trial enrollment, and reasons for non-enrollment. We used Fisher’s exact test for determination of P values. This abstract addresses patient demographics. Results: Of the 1,589 patients screened during this period, 359 were enrolled, for an overall accrual rate of 23%. The accrual rates among the various demographic subsets are shown in the table. No disparity based on gender, ethnicity, or race between Whites and African Americans (P value for the latter comparison 0.59) was found and the disparity gap between the young and elderly appears narrowed when compared to historical data (3-fold difference; Murthy VH, et al JAMA 2004). Conclusions: NCCCP has captured clinical trial screening and accrual outcome among several underserved populations coming from diverse geographic locations. Data suggests that through barrier identification and a concerted program of network strategies involving community cancer centers, disparities in clinical trial accrual have been reduced. This project funded in whole or part with federal funds from NCI, NIH under Contract No. HHSN261200800001E. # Screened # Enrolled Accrual rate (%) P Overall 1,589 359 23 -- Female 1,078 246 23 0.80 Male 511 113 22 Age > 65 689 143 21 0.09 < 65 883 216 25 Hispanic 93 20 22 0.80 Non-Hispanic 1,465 339 23 White 1,309 306 23 0.59 African American 205 44 22
Mutational landscape reflects the biological continuum of plasma cell dyscrasias
Authors: A Rossi, M Voigtlaender, S Janjetovic, B Thiele, M Alawi, M März, A Brandt, T Hansen, J Radloff, G Schön, U Hegenbart, S Schönland, C Langer, C Bokemeyer, M Binder
Journal: Blood Cancer Journal (2017)

Abstract We subjected 90 patients covering a biological spectrum of plasma cell dyscrasias (monoclonal gammopathy of undetermined significance (MGUS), amyloid light-chain (AL) amyloidosis and multiple myeloma) to next-generation sequencing (NGS) gene panel analysis on unsorted bone marrow. A total of 64 different mutations in 8 genes were identified in this cohort. NRAS (28.1%), KRAS (21.3%), TP53 (19.5%), BRAF (19.1%) and CCND1 (8.9%) were the most commonly mutated genes in all patients. Patients with non-myeloma plasma cell dyscrasias showed a significantly lower mutational load than myeloma patients (0.91±0.30 vs 2.07±0.29 mutations per case, P =0.008). KRAS and NRAS exon 3 mutations were significantly associated with the myeloma cohort compared with non-myeloma plasma cell dyscrasias (odds ratio (OR) 9.87, 95% confidence interval (CI) 1.07–90.72, P =0.043 and OR 7.03, 95% CI 1.49–33.26, P =0.014). NRAS exon 3 and TP53 exon 6 mutations were significantly associated with del17p cytogenetics (OR 0.12, 95% CI 0.02–0.87, P =0.036 and OR 0.05, 95% CI 0.01–0.54, P =0.013). Our data show that the mutational landscape reflects the biological continuum of plasma cell dyscrasias from a low-complexity mutational pattern in MGUS and AL amyloidosis to a high-complexity pattern in multiple myeloma. Our targeted NGS approach allows resource-efficient, sensitive and scalable mutation analysis for prognostic, predictive or therapeutic purposes.
Phase Ib study of ixabepilone (I) in combination with epirubicin (E) in women with metastatic breast cancer
Authors: H. H. Roché, M. Zambetti, F. Dalenc, S. Govi, L. Gladieff, B. Mudenda, I. Lainas, L. Iacono, L. Gianni
Journal: Journal of Clinical Oncology (2008)

1058 Background: Ixabepilone and anthracyclines are effective in the treatment of breast cancer. The primary objective of this phase I trial was to determine the maximum tolerated doses of the combination of epirubicin and ixabepilone. Methods: The safety, tolerability, pharmacokinetic and antitumor activity of epirubicin and ixabepilone in combination administered every 3 weeks was assessed in women with advanced breast cancer. Eligible pts with a cumulative dose of ≤ 300 mg/m2 for doxorubicin, ≤ 450 mg/m2 for epirubicin and ≥ 3 months of progression free interval after adjuvant anthracycline were enrolled. Three dose levels were explored in a 3 + 3 dose escalation design: epirubicin/ixabepilone at 75/25, 75/30 and 75/35 mg/m2. PK blood samples were collected during cycle 1 and estimated by non-compartment analysis. Results: Twenty-six pts have been enrolled to date, median age was 54 yrs (33–68). Eight pts received prior chemotherapy in adjuvant setting. Safety data are preliminary and available on 23 pts across the 3 dose levels for a total of 130 cycles (median 6 cycles, range 2–8). Neutropenia was the dose limiting toxicity, occurring in 1/6 pts at 75/25, 1/11 at 75/30 and 2/6 at 75/35 mg/m2. This included 1 pt with febrile neutropenia and 3 pts with grade 4 neutropenia of ≥ 5 days duration. Enrollment at 75/30 mg/m2 dose level is continuing. The most frequent grade 3 or 4 AE was neutropenia (4/23 and 15/23 respectively). Nonhematologic grade 3 and 4 toxicities were infrequent and included 2 pts with grade 3 neuropathy and 3 pts with grade 3 vomiting. No deaths were reported. No pharmacokinetic interaction was observed. Responses were seen at all dose levels tested. Of twelve women with measurable disease 10 achieved a partial response, one stable disease and one progressed. Six pts with non measurable disease had clinical benefit and/or no disease progression. Conclusions: Based on these preliminary data the recommended dose level of epirubicin 75 mg/m2 and ixabepilone 30 mg/m2 has a favourable toxicity and efficacy profile and warrants further investigation. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb Bristol-Myers Squibb Bristol-Myers Squibb
Robotic-assisted pancreaticoduodenctomy at a high-volume pancreas center.
Authors: A. H. Zureikat, D. L. Bartlett, J. L. Steel, A. J. Moser, H. Zeh
Journal: Journal of Clinical Oncology (2011)

258 Background: Robotic-assisted pancreatic surgery is gaining momentum due to improved ergonomics, dexterity, and visualization compared to standard laparoscopy. These technical advantages in combination with experience and improved robotic technology may reduce the significant morbidity associated with pancreaticoduodenectomy (PD). Methods: Retrospective analysis of consecutive robotic-assisted PD performed for all indications. Patients with potentially resectable tumors were selected for robotic PD on the basis of our EUS/CT predictive model. We evaluated perioperative events, final pathology, and complications occurring within the first 30 days on an intention-to-treat basis. Results: 42 robotic-assisted PD (22 women) were attempted between October 2008 and June 2010. Mean age was 67 years (SD=16, range 27-85), with median BMI 26.5 (IQR=7.8). 52.4% of patients had an ASA score of III. Final pathology included 13 pancreatic ductal adenocarcinoma, 9 peri-ampullary adenocarcinoma, 8 pancreatic neuroendocrine tumors, 5 IPMN, 2 cholangiocarcinoma, 2 pseudo-papillary neoplasm, 1 serous cystadenoma, 1 mucinous cystic neoplasm, and 1 duodenal adenoma. The first 34 patients underwent classic PD, and the final 8 patients had pylorus-preserving PD. Conversion to open was necessary in 8 patients (19%). Mean operative time was 576 min (SD=327, range 327-848 min) with 400mL median estimated blood loss (IQR=475). For malignancies, the R0 resection rate was 88% (4/34) with mean lymph node harvest of 17 (SD=7.3, range 8-37). The pancreatic fistula rate was 21% with ISGPF Grades B and C leaks observed in 9.6%. 10 patients (23.8%) developed minor complications (Clavien grade 1/2), whereas 11 had major complications (26.2%). There was one late death (2.4%). Median length of stay was 10 days (IQR=5). Statistically significant reductions in estimated blood loss (643mL vs. 317mL, p=0.003) and conversion to open (7 vs. 1, p=0.02) were observed in the latter half of the series. Conclusions: Robotic-assisted PD can be performed safely with postoperative and oncologic outcomes comparable to open surgery. The learning curve continues to evolve after 40 cases. No significant financial relationships to disclose.
STUDIES ON TYPHUS FEVER
Authors: Hans Zinsser, M. Ruiz Castaneda
Journal: The Journal of Experimental Medicine (1931)

Mexican typhus virus can be passed through ticks by the method of rectal injection. The virus will remain alive in the ticks for at least 12 days. These studies, together with one of our preceding publications and the work of Dyer, demonstrate that there are at least three insects-bedbugs, fleas and ticks-which must be considered as possibilities in conveying typhus fever from an animal reservoir to man. Our work will be continued by a study of rats and mice caught in typhus regions such as Mexico City and its immediate vicinity, with a search for the virus in these rodents as well as an analysis of the insects found upon them or in the localities in which they are concentrated.
Timing in adjuvant chemotherapy (CTX) initiation among women with breast cancer (BC) at National Comprehensive Cancer Network (NCCN) centers: An analysis from the NCCN Outcomes Database.
Authors: J. L. Vandergrift, J. C. Niland, R. L. Theriault, S. B. Edge, Y. Wong, L. S. Loftus, T. M. Breslin, C. Hudis, S. H. Javid, H. S. Rugo, S. M. Silver, E. M. Lepisto, J. C. Weeks
Journal: Journal of Clinical Oncology (2011)

6022 Background: Receipt of quality care has two important dimensions: that patients receive both appropriate and timely care. The primary aim was to examine time from BC diagnosis to CTX and identify factors associated with longer time. Methods: In the NCCN Outcomes Database, we identified 5,583 women with stage I-III BC diagnosed in 2003-2008 who received adjuvant CTX at 10 NCCN centers within 32 weeks (wks) of diagnosis. Patients with neoadjuvant therapy were excluded. Multivariate ANCOVA models were constructed to examine adjusted mean Time to Chemotherapy (TTC) from the date of pathological diagnosis. Results: Mean TTC was 11.8 wks. Many sociodemographic and clinical factors were associated with longer TTC. Factors with the largest effects are listed in Table 1. Minimal prolongation of TTC was associated with initial mastectomy versus lumpectomy (3 day greater TTC, p=0.01). Greater prolongation of TTC was observed between Caucasian and African American (AA) women diagnosed at another center prior to presentation (2.1 wks, p<0.001) than at the NCCN center (1.0 wk, p=0.13), and among patients with Medicare (2.7 wks, p<0.001) versus Managed Care (MCO, 1.2 wks, p<0.001) or Medicaid (0.9 wks, p=0.99). Interactions were significant between ethnicity and both insurance (p=0.03) and diagnosing institution (p=0.02). Conclusions: Some delay in TTC associated with clinical factors (21 gene RT PCR assay or number of excisions) may be unavoidable but should be minimized. Opportunities for improvement at the system level (insurance and transfers in care) were observed. Observed disparity in TTC for AA women appears to be exacerbated by transferring care and insurance related issues. % patients Mean TTC difference, wks Race/ethnicity Caucasian 78 Ref Hispanic 7 +0.7** AA 9 +1.6*** Asian 4 0.5 Other 2 0.0 Insurance MCO 78 Ref Medicare 10 +0.6* Medicaid 7 +2.6*** Other 4 0.4 Diagnosing institution NCCN 26 Ref Non-NCCN 74 +1.2*** Excisional procedures 1 64 Ref 2 31 +2.1*** ≥3 5 +5.6*** Reconstruction prior to CTX No 82 Ref Yes 18 +2.5*** 21-gene RT PCR assay No 94 Ref Yes 6 +2.2*** *p<0.05, **p<0.01, ***p<0.001
Psychotropic and stimulant medication (PSM) use among testicular cancer survivors (TCS): A multi-institutional clinical study of 680 patients given cisplatin-based chemotherapy (CHEM) (NCI 1R01 CA157823-02).
Authors: Somer Case-Eads, Lois B. Travis, Chunkit Fung, Howard D. Sesso, Darren R. Feldman, David J. Vaughn, Robert James Hamilton, Eileen Johnson, Derick R Peterson, Sophie D. Fossa, Lawrence H. Einhorn, Clair Beard
Journal: Journal of Clinical Oncology (2016)

242 Background: Testicular cancer (TC) is the most common cancer in men aged 15-40, with survival rates after diagnosis &gt; 95%. Testicular cancer survivors (TCS) are known to be at increased risk for certain acute and chronic medical conditions, but few studies have examined barometers of their psychological health. The objective is to characterize the prevalence of PSM use and associations with demographics, health behaviors, and treatment-associated toxicities among TCS. Methods: TCS aged &lt; 50 years at first-line CHEM completed a questionnaire regarding co-morbidities and prescription drug use, including PSMs. For co-morbidities, peripheral neuropathy (PN) responses of ‘a little’, “quite a bit”, or “very much” were scored ‘yes.’ Fisher’s exact test was used to examine the significance of various associations. Results: Among the first 680 consecutively enrolled TCS, median age at TC diagnosis was 31y (range, 15-49y) and median time since CHEM completion was 52mo (range 12-360mo). 85 TCS (12.5%) reported PSM use, including antidepressants (N = 65 [76.5%]), anxiolytics (N = 23 [27%]), and stimulants (N = 21 [25%]) with 20 TCS on ≥ 2 PSMs (23%). Compared to non-users, more PSM users were unemployed (11.8% vs. 4.4%%; P &lt; .01), self-rated their health as fair/poor (12.2% vs 4%; P &lt; .01), and had gained &gt; 20lb since CHEM (39.8% vs 23.4%;P &lt; .01). PSM users were more likely to have tinnitus (49.4% vs. 36.4%; P &lt; 0.04), both tinnitus and PN (43.5% vs. 27.2%; P &lt; 0.01), cardiovascular disease (26.2% vs. 15.6%; P &lt; .02), and greater use of prescription medications for pain control (20% vs. 4.7%; P &lt; 0.01), hypertension (16.5% vs. 7.1%; P &lt; 0.01), diabetes (8.3% vs. 2.9%; P &lt; 0.02), and testosterone replacement (10.6% vs. 5.0%; P = 0.048). Conclusions: Future studies should aim for identification of high-risk patients in need of intensified preventive and therapeutic interventions.
Pilot study of incorporating a supportive care program into a small community oncology practice.
Authors: Karly Kalstrom, Kelly Schultz, Jennifer Thompson, Michael Thomas Byrne, Andrew J. Buresh, Brendan F. Curley
Journal: Journal of Clinical Oncology (2016)

149 Background: Incorporation of supportive care has become standard of care in patients with advanced or metastatic cancer undergoing palliative chemotherapy. Implementation of a supportive care program is often difficult in a small community practice due to a multitude of factors. Methods: We piloted a supportive care program with the partnership of Sage Hospice &amp; Palliative Care in which patients with advanced or metastatic cancer undergoing chemotherapy would be evaluated by a certified nurse practitioner (CNP). Patients were selected for evaluation based on age, stage of cancer, and likelihood of needing additional supportive measures during their oncologic treatment. Patients were enrolled in the program by seeing the CNP and being followed throughout their chemotherapy, or until their death. Home visits were done by the CNP after hours, on weekends, or during business hours if it was noted to be medically necessary. Results: Forty-four patients were enrolled in the supportive care program. All patients either had metastatic or advanced cancer that required chemotherapy. The most common diagnoses are breast, pancreatic, prostate and lung cancer. The average number of patient home visits was 3.35 visits. Interventions varied, but the most common tasks performed were IV hydration, pain control and symptom management. Of the 44 patients, only 7 required an inpatient stay (15.9%) and none of these patients required a second hospital stay or were noted to be a 30 day readmission. Ten patients were enrolled in hospice, and 7 of those patients died. Zero patients died while on treatment or died without being enrolled on hospice. Conclusions: Incorporation of a supportive care program is feasible in a small community practice. The benefits may include improved patient outcomes, decreased hospitalizations, and smoother transition to end of life care.