tbuckley/cabot-search huggingface dataset:
U.S. regional practice patterns in metastatic renal cell carcinoma (mRCC) patients: A real-world retrospective analysis.
Authors: Sumanta Kumar Pal, Magdaliz Gorritz, Steven A. Sherman, Zhimei Liu
Journal: Journal of Clinical Oncology (2014)

505 Background: The treatment landscape for metastatic renal cell carcinoma (mRCC) has changed in recent years, with several targeted therapies becoming available for 1 st and 2 nd line use. The rapidly evolving treatment landscape has left physicians with an abundance of choices for the treatment of mRCC patients. This study aimed to understand whether this has resulted in varying treatment patterns across US regions in 1 st and 2 nd line targeted therapy for mRCC. Methods: RCC patients who initiated 1 st line targeted therapy with a vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFr) or mammalian target of rapamycin (mTOR) inhibitor between January 1, 2004 and June 30, 2011 were identified in the MarketScan database. First-line therapy was defined as the first claim in the database for a targeted therapy. One drug claim was sufficient to establish a line of therapy and a new line was defined as switching to another agent. Treatment patterns in the 1 st and 2 nd line settings were assessed in patients who initiated 2 nd therapy line after FDA approval of everolimus (Ev) (March 30, 2009) and stratified by geographic region. Results: Of the 6,524 patients included in the study, 1,298 (36%) received a 2 nd line targeted therapy after March 30, 2009. Although all possible permutations of treatment sequences were observed, overall, sunitinib (Su) and temsirolimus (Te) combined made up 80% to 83% of the 1 st line regimens across regions. The most common sequence was Su-&gt;Ev, observed in 18% of patients in the North Central US to 31% in the Northeast; Su-&gt;Te was the next most common sequence in all regions. Among patients who received 1 st line temsirolimus, the majority initiated 2 nd line on either bevacizumab (Be) (7%-12%) or Su (6%-10%) across regions. Conclusions: The most common treatment sequences across all regions were Su-&gt;Ev and Su-&gt;Te. Although a consistent pattern of sequential therapy emerged across regions, a wide range of on- and off-label strategies was observed outside of the predominant pattern of care. Furthermore, very few patients in this study received additional targeted therapy after 1 st line. Further research is needed to identify factors influencing these treatment strategies.
Comparative effectiveness of a patient centered pathology report for bladder cancer care.
Authors: Matthew Mossanen, Liam Connor Macleod, Alice Chu, Jonathan L. Wright, Daniel W. Lin, Bruce L. Dalkin, Lawrence D. True, John L. Gore
Journal: Journal of Clinical Oncology (2016)

420 Background: We compared the effectiveness of a patient-centered (PC) version of bladder biopsy pathology reports derived from PC outcomes research methods with standard pathology reports. Methods: Local bladder cancer experts provided consensus on the important elements of a bladder biopsy pathology. Patient focus groups reviewed these elements and identified PC formats and language. Candidate reports were iterated with patients to arrive at a pilot PC bladder biopsy report. We enrolled 40 patients undergoing bladder biopsy for suspicion of initial or recurrent bladder cancer. Block randomization was performed to the standard report or the standard report and the pilot patient-centered pathology report (PCPR). Through web-based surveys, we assessed self-efficacy with the PEPPI (Perceived Efficacy in Patient-Physician Interactions), physician communication with the CAT (Communication Assessment Tool), knowledge based on comprehension of report elements prioritized by experts, and format preferences at pathology disclosure and one month later. We compared study groups with descriptive statistics. Results: The 26-member expert clinician panel identified stage, grade, and histology as the most important elements of a pathology report. Patients prioritized data expressed in a narrative format, an illustration of tumor stage, and risk stratification for future recurrence. From July 2014 to 2015, 39 patients completed initial and follow-up assessments. Patients that received the PCPR had an improved ability to identify their cancer stage (initial 58% vs 20%, p = 0.02; follow-up 47% vs 15%, p = 0.03) and trended toward improved identification of cancer grade (initial 74% vs 50%, p = 0.12) compared with patients that only received standard reports. Ratings of patient self-efficacy did not differ by report format and communication trended toward improved communication for patients exposed to PCPR. Conclusions: PCPR are associated with greater patient knowledge about their new cancer diagnosis and may aid patient-provider communication around a new cancer diagnosis. While these results require validation in larger cohorts, this pilot may serve as a model for the development of PCPR for other cancers.
First-in-human dose escalation safety and pharmacokinetic (PK) trial of a novel intravenous (IV) thrombospondin-1 (TSP-1) mimetic humanized monoclonal CovX Body (CVX-045) in patients (pts) with advanced solid tumors
Authors: D. S. Mendelson, M. Dinolfo, R. B. Cohen, L. S. Rosen, M. S. Gordon, B. Byrnes, I. Bear, S. L. Schoenfeld
Journal: Journal of Clinical Oncology (2008)

3524 Background: CVX-045 is a recombinant humanized monoclonal antibody fused to two TSP-1 mimetic, nonamer peptides. CVX-045 inhibits endothelial cell migration in vitro, and is anti-angiogenic in vivo. A TSP-1 mimetic CovX Body has potential as an anti-angiogenic intervention via a previously unexploited mode of action. Methods: Pts with advanced solid tumors and no known bleeding risk received CVX-045 administered in 3 pt cohorts (0.3, 1, 3, 6, 12 and 18 mg/kg) by once weekly IV infusions (4 wk cycles) over 90 min lowered to 30 min upon individual tolerability. DLTs were grade ≥ 3 AEs in cycle 1 not directly related to tumor progression. MTD was highest dose at which 0/3 or 1/6 patients experience DLT. Serum PK assessed by highly specific ELISA. DCE-MRI pre-dose, on Day 2–4 and Day 28, in pts dosed at 3 mg/kg and higher. Results: 18 pts (M/F 6/12) were treated, median age 58.5 years (range 33–82), median prior regimens 7 (range 2–19), ECOG performance status 0–1, and median weeks on study at cut off 9 (range 3–22). No cycle 1 DLTs were observed. No obvious dose dependencies related to safety. Common adverse events (Grade 1–2) included gastrointestinal (abdominal pain, nausea, anorexia, flatulence, diarrhea and constipation), anemia, headache, fatigue and general muscle weakness. One case of suspected infusion reaction (Grade 1) in a patient receiving the highest dose (18 mg/kg) administered over 60 minutes. 6 serious AEs (Grade ≥ 3), only one of which, a case of radiation pneumonitis complicated by infectious pneumonia, was thought to be possibly drug related. Cmax and AUC increased linearly with dose, mean β T1/2 98.5 hrs. DCE-MRI showed effects on flow (21 - 42% decr. in Ktrans) but not permeability (AUCBN(90)) in 2/3 pts in 12 mg/kg group and 1 pt in 6 mg/kg group. RECIST: unconfirmed PR in 1 pt with liver mets and SD currently 8 to 16 weeks in 5/12 pts. 12 mg/kg appears to be the appropriate dose for further study. Conclusions: CVX-045 is a well tolerated new therapy targeting angiogenesis by a novel pathway. PK results are consistent with once weekly dosing. There is preliminary evidence by DCE-MRI and RECIST to suggest biologic activity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration CovX Research, LLC CovX Research, LLC CovX Research, LLC
Efficacy of cabazitaxel and its relationship with predictors of poor response to second hormonal therapies (2d HT) in metastatic castration-resistant prostate cancer (mCRPC).
Authors: Stephane Oudard, Florence Mercier, Aude Flechon, Aline Guillot, Sylvestre Le Moulec, Gwenaelle Gravis, Philippe Beuzeboc, Christophe Massard, Karim Fizazi, Thibault De La Motte Rouge, Reza-Thierry Elaidi, Antoine Angelergues
Journal: Journal of Clinical Oncology (2013)

137 Background: Potential predictors of low response to 2d HT including new agents have been recently identified: high Gleason score, rapid progression with first androgen deprivation therapy (ADT), chemotherapy lines &gt;1 and low baseline testosterone (T) levels. We evaluated the influence of these factors on the efficacy of cabazitaxel (C), a new taxane developed to overcome docetaxel (D) resistance. Methods: Records of 84 consecutive mCRPC pts (median 67 yrs) treated with C for disease progression on D or after D were retrospectively collected in 8 French centers. Baseline characteristics, disease history, PSA response, overall survival (OS) and radiological or clinical progression-free survival (PFS) were collected. Results: At C initiation, 84% of pts were ECOG 0-1, 59% had pain and 24% received ≥2 prior chemotherapy lines. Metastases were located in bone (93%), lymph nodes (49%) and visceral/soft tissues (9%). Gleason score was 8-10 in 47%, median time to progression with first ADT was 20 months and median T was 0.1 ng/ml. Median number of C cycles received was 6 (range 2-14). Efficacy of C was not influenced by Gleason score, response duration to first ADT, prior number of chemo lines, or baseline T (table). Main grade ≥ 3 toxicities were neutropenia (32%), anaemia (17%), thrombocytopenia (8%), diarrhoea (6%), and febrile neutropenia (5%). There was no grade ≥3 peripheral neuropathy and no toxic death. Conclusions: This retrospective study suggests that C is effective and shows an acceptable safety profile. Efficacy was not influenced by predictors of poor response to 2d HT (high Gleason, short response to first ADT, Number of chemo lines, low T levels). If these results are confirmed in further investigations, cabazitaxel could be proposed whatever the baseline characteristics of mCRPC pts. [Table: see text]
Prognostic relevance of genetic aberrations in gastrointestinal stromal tumors.
Authors: N. N. Mazurenko, I. S. Beliakov, I. V. Tsyganova, E. M. Bardina, O. A. Anurova, I. M. Gagarin, E. V. Skoromislova, P. P. Arhiri, M. P. Nikulin, I. S. Stilidi
Journal: Journal of Clinical Oncology (2011)

49 Background: Gastrointestinal stromal tumours (GISTs) contain oncogenic KIT or PDGFRA tyrosine kinase (TK) mutations leading to disturbance of downstream signaling pathways that contribute to GIST pathogenesis. Additional genetic aberrations were found in GISTs, demonstrating the involvement of other genes important in tumor progression. The aim of the study was to evaluate the prognostic relevance of different TK mutations in GISTs and to analyze the additional genetic aberrations in GISTs according to mutational status. Methods: 180 GIST patients were examined for KIT (9, 11, 13, 17 exons) and PDGFRA mutations (12, 14, 18 exons) by direct sequencing of DNA obtained from microdissected tumor sections. Tumor tissue DNA from 44 GISTs patients was screened for loss of heterozygosity (LOH) at 11 microsatellite loci on 1p, 9p, 14q, 15q and 22q arms. Results: KIT and PDGFRA mutations were identified in 76.1% and 10% of GISTs, respectively. 13.9% GISTs had no mutations (wild type). Most of KIT mutations were located in exon 11 (65%) and exon 9 (9.4%). Prognostic significance of TK mutations was evaluated. There was a trend of better survival for patients with PDGFRA mutation then with KIT mutation or wild type GISTs. The higher overall survival prior to target therapy was shown for patients with duplication or point mutation in KIT exon 11 in comparison to exon 11 deletion. Analysis of LOH revealed allelic deletions in 85% of GISTs, more frequently at 14q arm. There was a different LOH pattern in subgroups of GISTs. GISTs with PDGFRA mutation and with KIT exon 11 point mutation had LOH at 14q, while GISTs with KIT exon 11 deletions revealed high LOH frequency also on 22q, 15q and 1p arms. LOH in wild type GISTs occurred on all chromosomes with low frequency. LOH on 9p was found exclusively in metastatic and recurrent GISTs. Specific gene loci of frequent LOH were identified on 9p, 15q and 22q that may be contributed to GIST progression. Conclusions: Specific mutations are associated with GISTs prognosis. Tumors with point mutations and duplications in KIT exon 11 are associated with a better survival then GISTs with other KIT mutations. Specific pattern of allelic deletions was identified in subgroups of GISTs according to type of mutation and tumor progression. No significant financial relationships to disclose.
Correlation of production of IL-17 with immune suppression relating myeloid-derived suppressor cells (MDSC) and nutritional damages in patients with digestive system cancer.
Authors: Kenji Gonda, Masahiko Shibata, Takashi Yazawa, Rei Yashima, Takashi Kimura, Akira Kenjo, Izumi Nakamura, Shinji Ohki, Takayuki Anazawa, Takao Tsuchiya, Tatsuo Shimura, Yoshihisa Koyama, Mitsukazu Gotoh, Seiichi Takenoshita
Journal: Journal of Clinical Oncology (2013)

437 Background: Although a causal relationship between inflammation and innate immunity of cancer is more widely accepted today, many of the precise cellular mechanisms mediating this relationship remain unclear. Th17 cells, which produce the proinflammatory cytokine IL-17, have been recognized as one of the key factors in regulation of inflammatory bowel disease and rheumatoid arthritis. Methods: This study demonstrated that, in patients with digestive system cancers including 7 patients with esophageal, 14 with gastric, 20 with colorectal, 5 with hepatocellular, 7 with cholangiocellular, and 7 with pancreatic carcinomas, IL-17 production was correlated with MDSC level and with markers for nutritional impairment, immune suppression and chronic inflammation. Results: IL-17 production was significantly higher in patients with all types of digestive cancer than in normal volunteers. In addition, IL-17 production levels were significantly correlated with neutrophil counts and the neutrophil/lymphocyte ratio, and significantly inversely correlated with cell mediated immune response indicators (lymphocyte PHA-blastogenesis and IL-12 production) and patients’ nutritional status (prealbumin levels). Circulating MDSC levels were significantly correlated with IL-17 production. Conclusions: These results suggest that, in human gastrointestinal cancers, chronic inflammation involving IL-17 may be an important mechanism for disease progression through enhancement of immune suppression or cachexia. Controlling activation of Th17 cells may prove to be a valuable strategy for treatment of patients with gastrointestinal cancer.
Clone and initial identification of differentially expressed genes of human small cell lung cancer (SCLC) multi-drug resistance (MDR) cell line.
Authors: G. Wu, K. Li
Journal: Journal of Clinical Oncology (2010)

e21110 Background: Objectives: to build the subtracted cDNA library of differentially expressed genes of SCLC MDR cells and to detect the expression of some differentially expressed cDNA fragments in SCLC MDR cells and various tumour cells, using a cell line created in the preliminary research. Methods: The tester is SCLC MDR cell H446/CDDP cDNA, the driver is H446 cDNA; SHH and T/A cloning technology were done to build the subtracted cDNA library of differentially expressed genes of SCLC MDR cells in this research. The dot blot hybridization, sequencing and homology analysis were used to obtain differentially expressed cDNA fragments. Semi-quantitative RT-PCR and Northern blot were used to detect the expression of PDE2A and I- 2PP2A in seven tumour cells including SCLC cell H446, SCLC MDR cell H446/CDDP, adenocarcinoma cell A549, MDR cell A549/CDDP, hepatoma carcinoma cell SK-HEP-1, B lymphoma cell Namalwa and gastric adenocarcinoma cell SGC7901. Results: The study successfully built the subtracted cDNA library of differentially expressed genes of SCLC MDR cell H446/CDDP and obtained 21 differentially expressed cDNA fragments of cell H446/CDDP. Sequencing and homology analysis shows that the 21 fragments respectively represent 6 known genes (96%–100% homology). Semi-quantitative RT-PCR and Northern blot show that PDE2A expresses only in H446/CDDP. I-2PP2A expresses in H446, H446/CDDP, and Namalwa. Image analysis and statistical treatment show that I-2PP2A expression in H446/CDDP is significantly higher than that in H446 (p < 0.01) and that I-2PP2A expression in H446/CDDP is not significantly different from that in Namalwa (p > 0.05). Conclusions: Gene PDE2A and gene I-2PP2A have differential expression in SCLC MDR cell H446/CDDP. The two genes might participate in the formation of the MDR in H446/CDDP. Further studies are needed to determine how the two genes function in SCLC MDR mechanism. No significant financial relationships to disclose.
Nurse navigation: The key to a seamless transition.
Authors: Joy M. Fulbright, Wendy McClellan, Gary C. Doolittle, Hope Krebill, Robin Ryan, Kyla Alsman, Becky N. Lowry
Journal: Journal of Clinical Oncology (2016)

84 Background: Children's Mercy (CM) established a cancer survivorship clinic that cares for approximately 180 survivors a year. A third of the survivors are 18 years or older requiring transition to adult care. The importance of transitioning childhood cancer survivors from pediatric oncology care to adult primary care has been acknowledged in literature, but obstacles remain. Barriers include patient and provider anxiety, difficulty navigating the complex health care system and lack of knowledge regarding late effects. CM and The University of Kansas Cancer Center (KUCC) collaborated to decrease barriers to transition for childhood cancer survivors. Methods: The work group met for 2 years to develop the clinic at KUCC. Models and delivery of survivorship care, including the breast cancer survivorship clinic at KUCC, were reviewed. A shared nurse navigator was identified as an essential component to a seamless transition. Philanthropic support was obtained and job description was developed. Contracts were negotiated to allow the navigator to be present at both institutions. Results: The Survivorship Transition Clinic (STC) at KUCC launched July 2014, with a navigator supporting patients at CM as they begin their transition. The same navigator then meets with the patient at KUCC STC as they initiate care. The navigator provides treatment summaries, patient education and navigates the referral services for survivors. Since clinic launch, 16 survivors out of 16 have successfully transitioned from pediatric to adult survivorship care. Positive feedback was received from patient satisfaction surveys that were administered. A common theme showed a relief from anxiety due to having a contact person to facilitate communication among providers in a complex healthcare system. Conclusions: The nurse navigator has minimized anxiety about transition for patients and parents as she establishes a relationship with patients at CM, and then is able to provide continuity as they transition to the STC at KUMC. The navigator also improves communication between pediatric providers, adult primary care providers and sub-specialists caring for the patients. Overall, our transition process has been effective and is now serving as a model across both institutions.
Value of NADiA ProsVue on the CAPRA-S nomogram for predicting postprostatectomy clinical recurrence.
Authors: Judd W. Moul, Hans Lilja, Raymond Lance, Robert Vessella, Jonathan E. McDermed, Mark J. Sarno, Thomas H. Adams
Journal: Journal of Clinical Oncology (2013)

139 Background: The post-radical prostatectomy (RP) CAPRA-S nomogram stratifies men into low, intermediate and high risk groups for biochemical recurrence (BCR) and proved accurate for predicting 3 and 5 year BCR rates in a large study cohort. NADiA ProsVue is a prognostic test that identifies men at reduced risk of clinically recurrent prostate cancer when used with traditional risk factors. We assessed ProsVue, a prognostic test for identifying post-RP clinical recurrence, in an independent population of men classified into low, intermediate and high CAPRA-S risk groups. Methods: The 304 men in the ProsVue 510(k) study were categorized into low (scores 0-2), intermediate (3-5) and high (≥6) CAPRA-S risk groups. Men were categorized as “at reduced risk” or “not at reduced risk” using a 2.0 pg/mL/month ProsVue cutpoint. Clinical recurrence was defined by positive biopsy or imaging results or death due to prostate cancer. Clinical progression-free survival (cPFS) was determined between subgroups using univariate Cox regression and Kaplan-Meier survival analyses and Wilcoxon and log-rank p values were reported. Results: Recurrence occurred in 8/156 (5.1%), 20/93 (21.5%) and 32/55 (58.2%) of men in the low, intermediate, and high CAPRA-S risk groups, respectively (P&lt;0.0001). After 3, 5, 8 and 15 year followup, men in all CAPRA-S risk groups with ProsVue results ≤2.0 had significantly longer cPFS compared to men with results &gt;2.0. The differences are marked as early as 3 years post-RP in the intermediate and high risk groups. Conclusions: ProsVue added significant prognostic value for identifying risk of clinical recurrence within low, intermediate and high CAPRA-S risk groups. ProsVue is the strongest independent predictor of clinical recurrence of prostate cancer post-RP. [Table: see text]
Phase I study of the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888; V) in combination with irinotecan (CPT-11; Ir) in patients (pts) with advanced solid tumors.
Authors: P. LoRusso, J. J. Ji, J. Li, L. K. Heilbrun, G. Shapiro, E. A. Sausville, S. A. Boerner, D. W. Smith, M. J. Pilat, J. Zhang, A. P. Chen, N. Nechiporchik, R. E. Parchment
Journal: Journal of Clinical Oncology (2011)

3000 Background: The nuclear enzyme PARP is essential in recognition and repair of DNA damage. In preclinical models, PARP inhibitors work as sensitizing agents for DNA-damaging agents such as Ir. V is an orally bioavailable PARP 1 and 2 inhibitor. This phase I study determined the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), PK and PD of V together with Ir. Methods: Eligibility included patients with performance status 0-2; ≥ age 18; adequate bone marrow, hepatic and renal function. Cycles were 21 days. Ir was given i.v. 100 mg/m2 over 90 min on Days 1 and 8. Twice daily (BID) oral dosing of V (10-50mg) occurred Days 3-14 (Cycle 1) and Days -1-14 (subsequent cycles) followed by a 6-day rest. PK studies were conducted with both agents alone and in combination. Tumor biopsies and matched peripheral blood mononuclear cells (PBMCs) were collected for PD evaluation of PAR, γ-H2AX, PARP1, TOPO1, and ERCC1 after Ir alone and after the combination. Results: 32 pts were treated (2 lung, 14 breast, 4 esophageal, 7 ovarian, 4 colon, 1 anal). Median age was 53 (range 31-73). Most frequent drug-related toxicities included: diarrhea (59%), nausea (56%), leucopenia (50%), fatigue (47%), neutropenia (47%), anemia (34%), and vomiting (31%). DLTs included fatigue, diarrhea, febrile neutropenia (gr 3), leukopenia and, neutropenia (gr 4). Response has been determined for 28 pts. A clinical benefit (CB) rate of 61% (5 PR, 2 MR, 10 SD) was observed. V exhibited linear PK over the dose range of 10 to 50 mg BID; co-administration of Ir did not affect PK of V. Exploratory analysis of pre/post-V treatment changes indicated median ERCC1 levels in tumor tissue and PBMCs differed somewhat by CB status. PAR levels in paired tumor biopsies showed > 50% reduction in 17 of 19 pts and > 90% reduction in 10 of 19 pts. Conclusions: The MTD and recommended phase II dose was established as 100 mg/m2 of Ir given i.v. Days 1 and 8 combined with 40 mg of V given BID 15 days on/6 days off (21 day cycle). Exploratory analysis demonstrated that V reduced PAR levels in tumor. Support: NCI U01-CA062487 and NCI R21-CA135572.