tbuckley/cabot-search huggingface dataset:
Treatment patterns of tenosynovial giant cell tumor among commercially insured patients: A retrospective claims analysis.
Authors: Feng Lin, Chunlin Qian, Jackie Kwong
Journal: Journal of Clinical Oncology (2018)

e18737 Background: Tenosynovial giant cell tumor (TGCT) is a rare and locally aggressive tumor that arises from synovium in joints, bursae, and tendon sheaths. The objective was to examine treatment patterns of TGCT in real-world setting. Methods: A retrospective claims analysis was performed using the IQVIA Real-Word Data Adjudicated Claims - US Database. Adults who were diagnosed with TGCT (ICD-9: 727.02, 719.2x; ICD-10: D48.1, D21.x, M12.2) between 2011 and 2015 and did not have any TGCT diagnosis in 2 years pre-index were followed until the end of enrollment. Post-index surgeries were identified via claims for amputation, arthrodesis, arthroplasty, arthroscopic excision, and excision. Time from diagnosis to the 1st surgery and risk of recurrent TGCT that required reoperation were examined using survival analysis. Results: A total of 13,994 TGCT patients were identified (median age: 54; female: 58%), with 63% diagnosed between 45 and 64. Median follow-up was 28.5 months. Fifty one percent of patients (7199) had ≥1 surgery in the post-index period, with 73% (5245), 21% (1477) and 3.4% (477) having 1, 2 and ≥3 surgeries, respectively. Median time from diagnosis to the 1st surgery was 563 days. The risk of recurrence was 21.51% at 1 year and 29.17% at 2 years after the 1st surgery, and 18.05% at 1 year and 29.02% at 2 years after the 2nd surgery. The most common procedures were arthroscopic excision, open excision, and arthroplasty, representing 56%, 21% and 19% of the 1st surgeries, respectively. Arthroscopic excision (46%), arthroplasty (30%), and open excision (15%) remained common as the 2nd surgery, but arthroplasty became more common (36%) than arthroscopic excision (30%) and open excision (15%) as the 3rd surgery. Radiation therapy was infrequent (1.5%) as the 1st surgical procedure, but accounted for 14% as the 3rd surgery. Amputation was rare ( < 1%) among the first three surgeries. Conclusions: Among newly diagnosed TGCT patients, surgery is a common treatment. As reoperation is often required for recurrent TGCT, further investigations assessing functional impairment associated with TGCT and post-surgical recovery are warranted to improve our knowledge of the burden of TGCT.
Immunogenicity of sipuleucel-T (Sip-T) in abiraterone (Abi)/enzalutamide (Enz) sensitive and resistant metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Eric Jay Small, Lawrence Fong, David I. Quinn, Charles G. Drake, Dwayne Campogan, Tuyen Vu, Nadeem Anwar Sheikh, Nancy N. Chang, Daniel Peter Petrylak
Journal: Journal of Clinical Oncology (2016)

5077 Background: Immune responses to Sip-T in mCRPC patients (pts) correlate with survival (NEJM 2010;363:411). Adding Abi or Enz to Sip-T does not blunt Sip-T immune responses (CCR 2015;21:3862; JCO 2015;33 suppl:abs 5040). It is unknown if pts with primary resistance (1ores) to Abi or Enz have impaired Sip-T immune responses. Methods: STAMP (NCT01487863) and STRIDE (NCT01981122) are similar randomized phase 2 studies. mCRPC pts received Abi (n=69) or Enz (n=52) concurrently (Con) with or sequentially (Seq) after Sip-T. In vitro immune activation was assessed by antigen presenting cell (APC) activation in each Sip-T product. In vivo immune responses were assessed by cellular (ELISPOT and proliferation assays) and humoral (ELISA) immune responses to target antigens PA2024 and PAP. Pts with a PSA decline from baseline (BL) of ³50% were defined as Abi/Enz sensitive (sens); those with <50% PSA decline had 1o res. Immune responses in Abi/Enz sens and 1ores pts were retrospectively analyzed, in each trial, in pooled Con vs Seq arms across trials, and for all pooled data. Results: The % of pts with Abi/Enz sens was similar across pooled arms (Con: 72%; Seq 68%). No differences were seen in in vitro or in vivo immune responses for Abi/Enz sens vs 1ores pts at any time point (see Table). Conclusions: The magnitude of in vitro and in vivo immune responses after Sip-T appear to be independent of androgen sensitivity (i.e. PSA decline) to Abi or Enz, suggesting that Sip T therapy may have a role in pts with primary Abi or Enz resistance. Clinical trial information: NCT01981122 and NCT01487863.All pooled data Abi/Enz sens (n=82) Abi/Enz 1o res (n=35) p value Age,* y 69 (43–88) 74 (57–91) <0.05 Gleason sum ³8, n (%) 51 (64) 19 (56) NS BL PSA,‡ ng/mL 13 (5–49) 31 (10–66) <0.01 BL LDH,‡ U/L 187 (161–214) 199 (164–218) NS Cumulative APC activation‡ 35.5 (26.7–43.5) 34.5 (28.6–43.9) NS T cell ELISPOT count‡,§ 16.3 (3.7–94.7) 13.8 (0.7–46) NS# T cell proliferation stimulation index‡,§ 10.9 (3.8–24.2) 8.7 (4.0–21.8) Antibody titers (ELISA)‡,§, x103 51.2 (12.8–102.4) 25.6 (6.4–102.4) Median (*range/‡IQR); (%); §wk 6 for PA2024; #NS = not statistically significant at any time point, i.e. BL, wks 2, 4, 6, 10, 14, 20, 26, 40, 52, 56 for PA2024 and PAP (data not shown).
Real-world outcomes of ponatinib in treatment of advanced gastrointestinal stromal tumors (GIST) after tyrosine kinase inhibitor (TKI) failure.
Authors: Michael C. Heinrich, Lisa McGarry, David Kerstein, Hui Huang
Journal: Journal of Clinical Oncology (2017)

e22508 Background: Imatinib is standard front-line treatment for advanced KIT+ GIST. For patients whose tumors progress on imatinib, sunitinib is indicated, followed by regorafenib for those with disease progression on both imatinib and sunitinib. Patients refractory to 2 prior TKIs typically experience rapid progression (median PFS: 4.8 mos for regorafenib; 0.9 mos for placebo [Demetri Lancet 2013]), and with failure of all approved TKIs, unmet need remains high. The oral TKI ponatinib, approved for TKI-refractory CML and Ph+ ALL, has shown activity in heavily-pretreated (76% with ≥4 prior regimens) advanced KIT+ GIST patients in a Phase 2, single-arm study (Heinrich ASCO 2015) at starting dose of 45 mg/day: clinical benefit rate (CBR = CR + PR + SD for ≥16 wks) of 37% and median PFS of 4.3 mos were observed in 30 patients with KIT exon-11-mutant GIST and CBR of 14% and median PFS of 2.0 mos in 15 patients whose GIST lacked a KIT exon 11 mutation. Methods: To examine real-world outcomes, we retrospectively identified patients receiving ponatinib off-label for GIST (ICD-9 171.5x, 171.9x) between 01Jan2014 and 31Dec2016 from sole-source US specialty-pharmacy records. Using patient, physician and pharmacy dispensing data, patient characteristics, treatment setting and dosing were noted, and duration of treatment (DOT) was examined using Kaplan-Meier techniques. Results: We identified 26 probable GIST patients receiving ponatinib over this 2-year period: 58% male; median age 57.5 yrs. Where reported, all received prior TKIs, but data for prior lines of therapy were incomplete. Most (69%) were treated in an academic setting, and the most frequent starting dose was 45 mg (77%). DOT ranged from &lt; 1 to &gt; 19 mos, with an estimated median DOT of 3.8 mos. At 3 mos, 61% of patients were estimated to remain on ponatinib, and at 6 mos, 34%. Conclusions: Available real-world data show that patients treated with ponatinib for TKI-refractory GIST had a median DOT of almost 4 mos, with 1/3 remaining on therapy for &gt; 6 mos. Using DOT as a surrogate for PFS, these results are consistent with Phase 2 study results, and suggest ponatinib may have activity in patients who have exhausted other treatment options.
P04.16 Tumor treating fields affect invasion properties and cell morphology of various cancer cells
Authors: R Schneiderman, M Giladi, E Zeevi, A Shteingauz, T Voloshin, Y Porat, M Munster, E Kirson, Y Palti
Journal: Neuro-Oncology (2018)

Tumor Treating Fields (TTFields) therapy is an approved modality for the treatment of glioblastoma. TTFields are delivered via continuous, noninvasive application of low intensity, intermediate frequency alternating electric fields. The antimitotic effects of TTFields have been extensively investigated. We explored other processes that may be affected by TTFields such as cellular invasion. Human glioma, human and mouse melanoma, human breast cancer and human colon cancer cell lines were treated with TTFields using the inovitro system. Invasion assays were performed using a modified Matrigel coated Boyden chamber. TTFields effect on cells size, focal adhesions and stress fibers morphology was studied using immuno-fluorescent confocal microscopy. Invasion was significantly reduced compared to untreated cells in all tested cell lines. Furthermore, the optimal frequency for inhibition of invasion in tested cells was 300 kHz while the optimal anti mitotic frequency leading to glioma cell death is 200 kHz. The inhibitory effect on migration was observed at electric fields intensities of 0.6 V/cm RMS which is below the 1 V/cm RMS threshold previously reported for induction of cell death. Combining TTFields with Bumetanide, an agent that inhibits cellular motility, resulted in further inhibition of glioma cell invasion. TTFields application resulted in an increase in cell size, as well as in focal adhesion size, number and peripheral distribution of the adhesion sites. Also, treated cells adopted a more flattened and spread shape in comparison with control cells. TTFields treated cells exhibit reduction in appearance of stress fibers and a dense meshwork of actin filaments around the entire cell periphery. Our results suggest that cancer cell motility is impaired by exposure to TTFields. The TTFields parameters (intensity and frequency) which led to the maximal inhibition of cellular motility are different from those required for exerting anti-mitotic effects. The alterations in cells morphology during exposure to TTFields may contribute to reduction in cell motility. Further studies are needed to elucidate the mechanism by which TTFields disrupts cellular motility in glioma cancer cells.
Pediatric preclinical testing consortium evaluation of the EZH2 inhibitor tazemetostat in orthotopic PDX models of pediatric brain tumors.
Authors: Xiao-Nan Li, Lin Qi, Mari Kogiso, Holly Brianne Lindsay, Stephen W Erickson, Yuelong Guo, Malcolm A. Smith, Beverly A. Teicher
Journal: Journal of Clinical Oncology (2018)

10551 Background: Tazemetostat (EPZ-6438) is an EZH2 inhibitor that has entered clinical trials both in pediatric and adult patients. Over-expression of EZH2, the catalytic subunit of Polycomb Repressive Complex 2 that catalyzes H3K27me3, has been detected in a series of pediatric malignant brain tumors. Methods: Expression of EZH2 mRNA was examined in 23 patient derived orthotopic xenograft (PDOX) mouse models (10 GBMs, 11 medulloblastomas and 1 ATRT) with comparison to normal tissue levels. H3K27me3 was evaluated with immunohistochemical staining and Western blotting. Tazemetostat (250 mg/kg and 400 mg/kg) was tested in 4 PDOX models (1 GBM, 2 medulloblastomas and 1 ATRT) both as a single agent and in combination with cisplatin (5mg/kg days 8 and 11) and/or radiation (2 Gy/day x 5 days). Kaplan-Meier estimate of median time-to-event, ratio in median time-to-event between the treated and control groups (EFS T/C), and EFS p values were calculated and compared between the treatment groups. Results: Over-expression of EZH2 mRNA was detected in all GBM models (34.6±12.7) and medulloblastoma models (6.2±1.7 in group 3, 6.0±2.4 in group 4) accompanied by increased H3K27me3. INI1 mutation was confirmed in the ATRT model. In 3/4 models, tazemetostat at 250 mg/kg caused significant extension of median survival times (P< 0.05), with EFS T/C ranging from 1.32 to 1.39. Increasing drug dose from 250mg/kg to 400mg/kg resulted in significant EFS prolongation only for the ATRT model (EFS T/C 1.39 vs 2.01). When compared with cisplatin and radiation used alone, tazemetostat was not significantly more active. When combined with cisplatin and/or radiation, tazemetostat did not significantly prolong survival compared to the standard therapy used alone. A group 3 medulloblastoma was not responsive to any treatment tested. Conclusions: Tazemetostat prolonged survival times in 3/4 PDOX models tested, with the greatest treatment effect observed in the INI1 mutant ATRT model at the higher 400 mg/kg dose. These data are consistent with the BBB in these PDOX models not preventing anti-tumor activity of tazemetostat. The addition of tazemetostat to standard therapies did not lead to improved survival.
Can CRM status on MRI predict survival in locally advanced rectal cancers: Experience from the Indian subcontinent.
Authors: Jay Rashmi Anam, Mihir Chandarana, Supreeta Arya, Ashwin Luis Desouza, Vikas S. Ostwal, Reena Engineer, Prachi Patil, Avanish Saklani
Journal: Journal of Clinical Oncology (2017)

e15167 Background: Neoadjuvant chemoradiation has become the standard approach for treatment of locally advanced rectal cancers. Magnetic Resonence Imaging (MRI) is the staging modality of choice in rectal carcinoma. Recent reports have studied the impact of MRI on local recurrence and survival both in treatment naïve and post treatment settings Methods: A retrospective analysis of prospective database was performed over a period of 1 year. All pretreatment patients with carcinoma of rectum were included in the study. The status of CRM on MRI was compared to that on the histopathology and as a predictor of recurrence and survival. For analysis, the MRI scans done for patients at presentation were labeled as MRI T . This included all patients irrespective of further treatment received. Patients who were treated with NACTRT had two MRI scans. The MRI at presentation in this subset of patients was labeled as MRI 1 and the reassessment MRI after NACTRT was labeled as MRI 2 . Thus, MRI 1 represented a subset of MRI T with locally advanced tumors treated with NACTRT. All the sets of MRI scans were analyzed separately for prediction of CRM involvement and for their effect on local recurrence and survival rates. Results: 221 patients were included with a median follow-up 30 months. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI T , MRI 1 and MRI 2 to predict CRM status were 50%, 62.3%, 96.5%, 5.6% and 61.8%, 50%, 55%, 95%, 6% and 54.7% and 77.8%, 63.7%, 98%, 11%, 64.5% respectively. On multivariate analysis pathological positive margins alone predicted a poor overall survival (OS) whereas involved CRM on pathology and pretreatment MRI predicted poorer disease free survival and OS Conclusions: CRM status on pathology remains the most important prognostic factor to impact overall survival, disease free survival and local recurrence. CRM status on MRI at presentation alone has significant impact on disease free survival and local recurrence. Although MRI done after neoadjuvant treatment may not predict survival, it has a role in helping modify the surgical approach with a goal to achieve a negative CRM on pathology.
Trajectories of anxiety among breast cancer patients treated with chemotherapy pre- and post-chemotherapy compared to healthy controls: A nationwide multicenter study.
Authors: Carly Lynn Paterson, Ann M. O'Mara, Charles E. Heckler, Victor Kipnis, Charles Stewart Kamen, Mary Ontko, Karen Schmidt, Jerry W. Mitchell, Michelle Christine Janelsins
Journal: Journal of Clinical Oncology (2017)

e21711 Background: A diagnosis of breast cancer (BC) elicits a myriad of concerns for women. Treatments are complex, often with multiple components, including chemotherapy. This study describes the trajectory of anxiety among BC patients treated with chemotherapy compared to healthy controls. Methods: This prospective observational study of breast cancer and lymphoma patients is being conducted through the National Cancer Institute Community Oncology Research Program (NCORP). For this analysis, women diagnosed with stage I-III BC and age-matched healthy controls were assessed using the State Trait Anxiety Inventory (STAI) at baseline prior to chemotherapy, 1-month and 6-months post-treatment. Baseline characteristics were compared using Welch’s t-test and chi-squared tests, and proportions of participants reporting anxiety between groups were examined at each time point. Linear mixed models (LMM) were used to compare anxiety trajectories over time, accounting for relevant baseline clinical, medical and demographic factors. Results: Among 945 participants, including 581 BC patients and 364 controls, the average age was 53 years, 91% were White, and 98% were non-Hispanic. Compared to controls, more BC patients reported anxiety scores &gt; 40 at baseline (35% vs. 13%), 1-month (31% vs. 16%), and 6-months (30% vs. 19%), indicating potentially clinically significant anxiety. While BC patients’ anxiety decreased after an apex at baseline, it remained significantly higher than controls’ anxiety at each time point (all p &lt; 0.001), and LMM analysis identified group and group by time interactions for each follow-up (all p &lt; 0.001). Among all participants, predictors of increased anxiety included younger age, post-menopausal status, lower baseline cognitive function and higher baseline depressive symptoms. Conclusions: BC patients reported higher anxiety than controls at all time points, providing further insight into the trajectory of anxiety pre- and post-chemotherapy. Research into optimal timing of assessment and appropriate interventions to minimize anxiety burden in this population is warranted. Clinical trial information: NCT01382082.
Evaluation of an immunotherapeutic DNA-vaccine in biochemically relapsed prostate cancer.
Authors: Neal D. Shore, Elisabeth I. Heath, Luke T. Nordquist, Heather H. Cheng, Kamalnayan Bhatt, Matthew Morrow, Trevor McMullan, Kimberly Kraynyak, Jessica Lee, Brian Sacchetta, Li Liu, Samantha Rosencranz, Scott T. Tagawa, Rahul Atul Parikh, Ronald F Tutrone, Jorge A. Garcia, Young E. Whang, William Kevin Kelly, Ildiko Csiki, Mark L. Bagarazzi
Journal: Journal of Clinical Oncology (2018)

5078 Background: The DNA immunotherapy, INO-5150 (PSA and PSMA) +/- INO-9012 (IL-12) was assessed for safety, immunogenicity and the effect on PSA kinetics in biochemically recurrent prostate cancer patients (pts). Methods: Phase I, open-label, multi-center study included pts with rising PSA after surgery and/or RT, PSA doubling time (PSADT) > 3 months (mos), testosterone > 150 ng/dL, no concurrent ADT and no evidence of metastases by conventional imaging. Safety, immunogenicity and efficacy were evaluated in 4 treatment arms in 60 planned pts (A: 16, 2mg INO-5150; B: 15, 8.5 mg INO-5150; C: 15, 2mg INO-5150+1mg INO-9012; D: 16, 8.5mg INO-5150+1mg INO-9012). Pts received 4 IM doses of vaccine followed by electroporation on day 0, wks 3, 12 and 24 and followed for 72 wks. Results: The study has concluded and 50/62 (80%) pts completed all visits. 90% of pts had Grade (Gr) 1-3 AEs, primarily injection site reactions which were Gr 1. Across 4 cohorts, 47/61 (77%) of all evaluable pts demonstrated immunogenicity, [35/58 (60%) had IFN-γ reactivity by ELISPOT, 6/61 (10%) and 5/61 (8%) had antibody titers against PSA and PSMA, respectively, and 19/50 (38%) had CD38, Perforin+CD8 T cell responses]. Pts (38%) with CD38 and Perforin + CD8 T cell immune reactivity had attenuated % PSA rise compared to non-reactive pts (p = 0.05, n = 50). Pts with no known progression during the study showed significant differences in log2PSA change and PSADT pre-treatment baseline (D0) vs wk 27 (post-immunotherapy time point, n = 34, p < 0.0001) or wk 72 (end of follow-up, n = 27, p < 0.0001). Furthermore, pts with D0 PSADT≤ 6 mos and no known progression during the study showed significant differences in log2PSA change and PSADT in D0 vs wk 27 (n = 15, p < 0.0001) or wk 72 (n = 10, p = 0.002). Conclusions: INO-5150 +/- INO-9012 was safe, well tolerated and immunogenic. A clinical effect was demonstrated by evidence of dampening % rise in PSA and increased PSADT in the majority of patients. In patients with no known disease progression during the study, a significant PSA stabilizing effect of the immunotherapy was observed. Additional analyses are ongoing to further elucidate the correlation of immunologic efficacy and clinical benefit. Clinical trial information: NCT02514213.
Patient-reported comorbidity and survival in older adults with cancer.
Authors: Grant Richard Williams, Allison Mary Deal, Jennifer Leigh Lund, YunKyung Chang, Hyman B. Muss, Mackenzi Pergolotti, Emily Jean Guerard, Shlomit S. Shachar, Hanna Kelly Sanoff
Journal: Journal of Clinical Oncology (2017)

10033 Background: Our ability to optimize the care of older adults with cancer and comorbid illnesses is insufficient as most clinical trials lack systematic measurement of comorbidities. The primary purpose of this study was to evaluate the prevalence and impact of patient-reported comorbidity on survival using various comorbidity scoring algorithms. Methods: We utilized a unique linkage of the Carolina Senior Registry, an institutional registry (NCT01137825) that contains geriatric assessment data, with the North Carolina Central Cancer Registry to obtain mortality data. Comorbidity was assessed using a patient-reported version of the Older Americans Resources and Services Questionnaire (OARS) Physical Health subscale that includes information regarding 13 specific comorbid conditions and the degree to which each impairs function (“not at all” to “a great deal”). Multivariable Cox proportional hazard regression models were used to evaluate the association between comorbidities and all-cause mortality. Results: 539 patients were successfully linked to mortality data. Median age 72, 72% female, 85% Caucasian, 47% breast cancer, and 12% lung cancer. 92% of participants reported at least one comorbid condition, mean of 2.7 conditions (range 0-10), with arthritis and hypertension the most common (52 and 50%, respectively). 62% of patients with a comorbid illness reported a functional limitation related to comorbidity. Both the presence of 3 or more total comorbidities (hazard ratio (HR) 1.44, CI 1.08-1.92) and 2 or more comorbidities impacting function (HR 1.46, CI 1.09-1.95) increased mortality. After adjusting for age, cancer type, and stage, the risk of death increased 12% for each comorbid condition impacting function (HR 1.12, CI 1.02-1.24), but did not significantly increase for the number of comorbid conditions alone (HR 1.07, CI 0.99-1.15). Conclusions: Comorbid conditions in older adults with cancer are highly prevalent, frequently impair function, and impact survival. Comorbid conditions that impair function have a greater impact on survival than the presence of comorbidity alone. Comorbidity assessment should be incorporated in clinical trials and can be measured via a simple one-page patient-reported questionnaire.
Abstract 19666: New Onset Atrial Fibrillation is Associated With Elevated Galectin-3 and Follistatin-Like 3 Levels
Authors: Dongqing Chen, Nathan Procter, Su Jen Chua, Vincent Goh, Saifei Liu, Bahador Assadi-Khansari, John D Horowitz, Doan T Ngo, Aaron L Sverdlov
Journal: Circulation (2016)

Background: Atrial fibrillation (AF) is a common cardiac arrhythmia, associated with increased risk of stroke and cardiac mortality. Atrial remodeling and atrial fibrosis have been suggested to participate in the pathogenesis of AF. Follistatin-like 3 (FSTL3) and Galectin-3 are secreted proteins that has regulatory roles in fibrosis, inflammation and tissue repair. Both have been reported to be associated with cardiac remodeling in heart failure. Furthermore, Galectin-3 levels have been shown to predict atrial remodeling and incidence of AF. Thus, in this study, we sought to examine whether differential FSTL3 and Galectin-3 levels predict chronicity of AF in patients. Methods and Results: 134 patients hospitalized with AF were evaluated (mean age 69±12 yrs). Of those, 34 patients (26%) were diagnosed with new onset AF. Plasma Galectin-3 and follistatin-like 3 (FSTL3) levels were measured by commercially available ELISA assay. On univariate analyses, patients with new onset AF had i) significantly higher G...