tbuckley/cabot-search huggingface dataset:
Efficacy and long-term safety with bevacizumab included in neoadjuvant and adjuvant therapies in patients with advanced ovarian cancer: Results of the ANTHALYA trial.
Authors: Florence Joly, Paul H. Cottu, Sebastien Gouy, Eric Lambaudie, Frédéric Selle, Eric Leblanc, Anne Floquet, Christophe Pomel, Elisabeth Chereau, Sarah Zohar, Julien Dupin, Sabine Balouet, Rose-Marie Ferri, Marisol Urbieta, Leila Kockler, Romain Rouzier
Journal: Journal of Clinical Oncology (2017)

5538 Background: ANTHALYA showed that neoadjuvant Bevacizumab (B) added to Carboplatin and Paclitaxel (CP) was well tolerated and achieved encouraging complete resection rates at IDS (58.6%) in unresectable FIGO stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma (EJC 2017;70:133–42). We report response rates, PFS and long-term safety. Methods: Patients (pts) in ANTHALYA were randomized 2:1 to 4 cycles (c) of neoadjuvant CP ±3 c of B (15 mg/kg), IDS for eligible patients, then 1 c of CP + 3 c CPB + 21 c of B. Response and progression were evaluated by RECIST 1.1 using CT scan and CA-125. Circulating tumor cell counts (CTC) were evaluated at baseline, c2 and IDS. Results: 95 pts were treated in CP (n=37) or BCP (n=58) groups (mean study duration were 16.1 months [mo] and 16.9 mo, respectively). 80 pts (CP: 81% / BCP: 88%) had a CA-125 response (50% reduction in CA-125 level) before IDS. Objective response rates were 65% (62% CP / 67% BCP) before IDS (28 days after c4), 46% at c8 (46% CP/ 47% BCP) and 19% at c26 (19% CP/ 19% BCP). 24 (64.9%) CP pts and 26 (44.8%) BCP pts progressed during follow up (median PFS 21.2 mo [95%CI: 14.5, 26.7] and 23.5 mo [18.5, 30.6], respectively). Median PFS was respectively: 25.8 mo (21.0, 30.0) and 17.1 mo (13.5, 22.2) for pts with/without complete resection at IDS; 21.0 mo (15.0, 25.4) and 25.8 mo (18.5, 27.2) for pts with/without baseline CTCs (n=29 / 59); 21.8 mo (17.5, 27.1) and 22.2 mo (15.3, 38.0) for pts with FIGO IIIC and IV tumors. 36 pts did not receive adjuvant therapy within the study (21 were unresectable for IDS), 59 pts (57% CP / 66% BCP) received it. Of those, 34 pts (52% CP / 61% BCP) had Grade ≥3 adverse events including neutropenia (29% CP / 34% BCP), HBP (10% CP / 8% BCP), proteinuria (10% CP / 0% BCP), deep venous thrombosis (5% CP / 3% BCP), pulmonary embolism (0% CP / 8% BCP). Conclusions: Neoadjuvant BCP followed by IDS and adjuvant BCP achieves high response rates and extended PFS with an acceptable toxicity in this specific population of pts with FIGO stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma not eligible for primary debulking surgery. IDS outcome and CTC counts should be further explored as long term prognostic factors. Clinical trial information: NCT01739218.
Effect of primary site on the prognosis in patients with advanced-stage cancer in palliative care settings (J-Proval): A multicenter prospective cohort study in Japan.
Authors: Shuji Hiramoto, Isseki Maeda, Mika Baba, Ayako Kikuchi, Akira Yoshioka, Yoshihisa Matsumoto, Hiroya Kinoshita, Tatsuya Morita
Journal: Journal of Clinical Oncology (2016)

10025 Background: There are few reports about patient’s prognosis depending on primary sites of cancer in palliative care settings. Methods: This study was conducted as a secondary analysis for a large prospective cohort study (J-Proval) that followed up patients between September 3, 2012 and April 30, 2014 from 58 palliative care institutions across Japan. We obtained data of 2290 patients including those in hospital palliative care teams, palliative care units and home palliative care services. We classified patients into seven categories depending on the primary site of cancer: lung (n = 506), gastro-esophageal (n = 317), colorectal (n = 272), biliary-pancreatic (n = 351), breast (n = 119), urological and gynecological cancer (n = 294), and others (n = 431). The primary endpoint was the actual survival time, measured from the start of registration, by cancer type. The secondary were the frequency of debilitating complications and end-of life treatment. Results: The median overall survival (mOS) time was 33 days (95% confidence interval [CI], 28 to 38 days), 28 (95% CI, 23 to 33), 40 (95% CI, 33 to 47), 28 (95% CI, 24 to 32), 34 (95% CI, 26 to 42), 42 (95% CI, 31 to 53) and 35 (95% CI, 29 to 41) for lung, gastro-esophageal, colorectal, biliary-pancreatic, breast, urological and gynecological, and other types of cancers, respectively. mOS was significantly shorter in both gastro-esophageal cancer and biliary-pancreatic cancer after adjustment for patients’ background. The incidence of delirium was lower in gastro-esophageal cancer (33.4%). The incidence of dyspnea was highest in lung (58.9%) and lowest in biliary-pancreatic cancer (30.0%). The incidence of appetite loss was highest in gastro-esophageal (88.3%). The proportion of patients who received artificial hydration in the final days of life was performed more frequently in patients with lung (63.5%), gastro-esophageal (60.2%), and colorectal (60.2%) cancers than in the total population. Conclusions: Our results show a significant difference in the survival time and the frequencies of distressing symptoms and end-of-life treatment depending on the primary site of cancer in palliative care settings.
Real world survival outcomes in patients with high risk stage II colon cancer at a Beijing Cancer Hospital.
Authors: Aiwen WU, Peng-ju Chen, Tian-le Li, Irene Dankwa-Mullan, Ting-ting Sun, Kyu Rhee
Journal: Journal of Clinical Oncology (2018)

e15670 Background: Overall survival (OS) and disease free survival (DFS) advantage conferred on patients with stage II colon cancer remains unproven and controversial. In addition, optimal adjuvant chemotherapy regimen for stage II disease remains debatable. The FOLFOX regimen was superior to short-term FU/LV in the MOSAIC trial, however, OS and DFS benefit was limited to stage III disease. An investigative analysis showed an absolute difference in 5-year DFS that favored FOLFOX in stage II patients with high-risk tumors, but it was not statistically significant. The SEER study showed no difference in median 5-years OS between patients in chemotherapy group and the surveillance group (56.1% vs 56.7%). The promise of precision medicine and cognitive technology tools such as IBM Watson for Oncology (WFO) may be beneficial for facilitating personalized treatment choices based on evidence and survival outcomes. Methods: This study leveraged WFO for treatment evidence comparison. We measured survival outcomes and prognostic factors for 229 patients with Stage II colon who received resection between 2006-2015. Five-year OS and DFS was examined using the Kaplan Meier survival analysis, and comparison of OS and DFS curve was performed by log rank test. Results: The 3-year OS, 5-year OS, 3-year DFS and 5-year DFS, were 92.1, 88.5, 87.2, and 83.0%, respectively. Patients that received chemotherapy had significantly higher 5-year OS than those received surveillance (94.9% vs 84.1%, p = 0.03). OS and DFS was significantly shorter in patients with 2 or more risk factors (log rank test, p = 0.01 and 0.02 respectively). Conclusions: Study showed overall superior OS and DFS compared to patients in real world studies including trials in WFO curated literature. Limitations of this study included use of retrospective cases, inadequate number of cases with 2 or more prognostic factors and uneven clinicopathological features for the analysis. Performance status and co-morbidities were not assessed, which may influence survival outcomes. Nonetheless this study was important for assessing survival outcomes in Chinese patients with Stage II colon cancer. This suggests need for further clinical trials targeting this group.
A Population-Based Study of Long-Term Morbidity in Pancreas Cancer Patients.
Authors: Katherine Elaine Fero, Neil Panjwani, Rayna Matsuno, James Don Murphy
Journal: Journal of Clinical Oncology (2016)

e15742 Background: Pancreatic cancer represents an aggressive disease characterized by early and relentless tumor spread. Appropriately, this pattern of progression leads healthcare providers to consider pancreatic cancer a “distant disease.” However, local tumor progression within the pancreas can lead to substantial morbidity. This study defines the long-term morbidity from locoregional and systemic disease progression in a large population-based cohort. Methods: We used the SEER–Medicare linked database to identify 21,878 individuals diagnosed with pancreatic cancer from 2000-2011. Hospitalizations identified from Medicare claims were attributed to either systemic (thromboembolic events, diarrhea, dehydration, emesis, cytopenia) or locoregional (biliary obstruction, GI bleed, gastric or small bowel obstruction, GI ulceration) complications. Competing risk analyses were used to determine the cumulative incidence of complications from locoregional and systemic disease. Multivariable Fine-Gray models were used to identify the impact of chemotherapy or radiotherapy on the risk of hospitalization. Results: Of the total cohort 7,577 (34.6%) patients were hospitalized for locoregional complications, and 7,269 (33.2%) for systemic complications. The average number of hospitalizations was 1.6 (SD 1.1), and the average length of stay was 8.4 days (SD 8.0). The unadjusted cumulative incidence of a locoregional complication at 6 months post-diagnosis was highest in unresectable patients (35.1%), followed by resectable (33.8%) and metastatic (24.5%) (p < 0.001). For systemic complications, the cumulative incidence was highest in metastatic patients (28%), followed by resectable (24.5%) and unresectable (22.8%) (p < 0.001). Multivariable analysis found that the use of radiation and chemotherapy reduced the risk of locoregional hospitalization by 56% and 18%, respectively (subdistribution hazard ratio [SDHR] 0.44, 95% CI 0.41-0.47 for radiation, and SDHR 0.82, 95% CI 0.76-0.89 for chemotherapy). Conclusions: Despite the predilection of distant disease spread in pancreatic cancer, both local tumor progression and distant metastatic disease lead to substantial morbidity that reduces quality of life.
P33 NRF2-MEDIATED UPREGULATION OF OSGIN1 AND OSGIN2 TRIGGERS CELL DETACHMENT THROUGH DYSREGULATED AUTOPHAGY – A POTENTIAL MECHANISM FOR ENDOTHELIAL EROSION OVERLYING STENOTIC PLAQUES
Authors: Sandro Satta, Michael Mcelroy, Georgina Hazell, Jack Teasdale, Graciela Sala-Newby, Jason Johnson, Frank Gijsen, Tom Johnson, Yvonne Alexander, Amir Kesmiri, Andrew Newby, Stephen White
Journal: Cardiovascular Research (2018)
Rhabdomyosarcoma in the first year of life: outcome data from five trials and one registry of the Cooperative Weichteilsarkom Studiengruppe (CWS).
Authors: Monika Sparber-Sauer, Sabine Stegmaier, Christian Vokuhl, Ivo Leuschner, Guido Seitz, Thekla von Kalle, Monika Scheer, Marc W. Muenter, Stefan S. Bielack, Bernarda Kazanowska, Ruth Ladenstein, Felix Niggli, Gustaf Ljungman, Thomas Klingebiel, Joerg Fuchs, Simone Hettmer, Ewa Koscielniak
Journal: Journal of Clinical Oncology (2018)

10534 Background: Infantile soft tissue sarcoma (STS) has been associated with worse survival than STS in older children. Age, histology, molecular phenotype and treatment adjustment according to age may affect the outcome of patients with rhabdomyosarcoma (RMS) diagnosed during the first year of life. Methods: The records of 5 trials and one registry, conducted by the Cooperative Studiengruppe (CWS) between 1981–2016, were reviewed to identify children diagnosed with RMS during the first year of life. Patient characteristics, treatment data and outcome were evaluated. Results: A total of 155 infants ≤ 12 months with histological diagnosis of RMS were identified, including 115 cases of embryonal RMS (RME), 38 cases of alveolar RMS (21/25 PAX7/3:FOXO1-positive (PF+)), 1 case of botryoid RMS and 1 case of spindle-cell RMS. 144 infants presented with localized disease (LD); 11 with metastatic disease (MD). 150 children received age- and weight-adapted chemotherapy (1/3 dose reduction in infants ≤6 months): VAIA/VACA/CEVAIE (n = 100), IVA/VA/VAC/other (n = 50). Resections were achieved R0 (n = 64), R1 (n = 37), R2 (n = 37) and biopsies (n = 17). Adjuvant radiotherapy (RT) was administered to 37 children. After a median follow-up of 7.55 years [0.24- 30], the 5-year overall survival (OS) and event-free survival (EFS) rates were 66% and 49% for the whole group. Significant prognostic factors were LD (OS 69% vs 12% in MD, p = 0.000), tumor size and resection status. For patients with LD, tumor size and best resection (R0/R1/R2) were no prognostic factors and RT did not improve survival. 2nd malignancy occurred in 6 infants. OS and EFS rates of newborns (≤1 month, n = 15) were significantly worse (31% and 17%, respectively) compared to those > 1 month and ≤ 12 months (n = 140, OS 69% and EFS 52%, p = 0.001 and 0.001). Children with RMA (41% and 24%) and/or PF+-RMS achieved significantly worse regarding OS and EFS (36% and 19%) than those diagnosed with RME (72% and 56%; p = 0.018 and 0.003). Conclusions: Survival of infants with RMS is comparable to older children. Metastatic disease, RMA histology/ PF+ status and age below 1 month are factors relevant for inferior outcome. RT did not improve survival in LD.
TCT-343 Variations in Efficacy and Safety Over Time Between Drug-Coated Balloon and Drug-Eluting Stent for the Treatment of Coronary In-Stent Restenosis: Results from the DAEDALUS Study.
Authors: Daniele Giacoppo, Fernando Alfonso, Bo Xu, Bimmer Claessen, Tom Adriaenssens, Christoph Naber, Maria Perez-Vizcayno, Do-yoon Kang, Ralf Degenhardt, Leos Pleva, Jan Baan, Duk-Woo Park, Runlin Gao, Jose PS. Henriques, Seung-Jung Park, Adnan Kastrati, Robert Byrne
Journal: Journal of the American College of Cardiology (2018)
Impact of the epigenetic modulator BORIS on sensitivity of melanoma cells to UV-induced DNA damage.
Authors: Sanne Janssen, Leon Van Kempen, Mounib Elchebly, Marie-Noel M'Boutchou, Alan Spatz
Journal: Journal of Clinical Oncology (2017)

e21077 Background: Cutaneous melanomas display considerably higher mutational load compared to other solid tumors, mainly due to DNA damage and absent/defective repair. Chromatin organization plays an important role in these processes, with open chromatin conferring a higher sensitivity to DNA damage. BORIS is an epigenetic modifier that is correlated with open chromatin and is abnormally expressed in primary and metastatic melanoma. Here we set out to obtain a better understanding of BORIS’s role in chromatin organization and DNA damage in melanoma. Methods: A panel of melanoma cell lines was selected and BORIS mRNA expression was determined using qPCR. Cellular localization of BORIS was assessed by immunofluorescence. Ectopic BORIS expression was established exploiting a doxycycline inducible expression vector and proliferation was assessed using crystal violet and Hoechst staining. DNA damage was induced by exposure to 60 J/m 2 UVC followed by apoptosis and cell cycle analysis using flow cytometry. Results: We confirmed aberrant BORIS expression in 61% of our melanoma cell line panel and observed nuclear BORIS localization in areas of low chromatin density. Forced expression of BORIS in BORIS low/intermediate cell lines resulted in a significant reduction in cell growth and increased cell death. Interestingly, BORIS overexpressing cells exposed to UV irradiation displayed a higher degree of cell cycle alterations and increased level of apoptosis compared to BORIS low/intermediate cells. Conclusions: Our results demonstrate that BORIS is increased in melanoma, localized in areas of open chromatin, and increased sensitivity to UV-induced DNA damage. Taken together, this indicates a role for BORIS in directing the chromatin state into a more open conformation, allowing increased sensitivity to DNA damage. Currently, we are analyzing DNA damage in BORIS overexpressing cells and are further investigating BORIS’s role in directing chromatin state by exploiting ATAC-seq and ChIP-seq for various epigenetic marks.
The effect of thoracic radiation on overall survival and their association with systemic immune therapy in stage IV NSCLC: Findings from the National Cancer Database.
Authors: Feng-Ming Spring Kong, Weili Wang, Gerg Durm, Jun Wan, Jianyue Jin, Wenhu Pi, Chen Hu, Mark P Langer, Tim Lautenschlaeger, Sophie Paczesny, Thomas J Birdas, Nasser H. Hanna
Journal: Journal of Clinical Oncology (2018)

9103 Background: The role of thoracic radiation (TRT) is controversial for stage IV non-small cell lung cancer (NSCLC). A prospective study of 29 patients reported superior progression free survival with radical TRT. This study aimed to report the overall survival (OS) effect of TRT and examine whether the OS effect varies with the timing of TRT regarding to systemic therapy. Methods: Stage IV patients from the national cancer database (NCDB) 2005-2014 formed the base of the study population. TRT, dose and time effects were analyzed individually in patients treated with non-immune systemic therapy or immune therapy. The primary endpoint was OS. Kaplan-Meier test was used for the OS analysis. Results: A total of 334,702 patients were eligible. Median survival time (MST) was 5.2 months (mo). Younger age, female gender, non-African American, lower Charlson comorbidity score, and any TRT were all significantly associated with favorable OS (all P < 0.001). In 326,287 patients receiving non-immune systemic therapy, TRT was a significant factor for favorable OS (HR = 0.964, 95%CI 0.955-0.974, P < 0.001). Comparing to those receiving TRT before non-immune systemic therapy (n = 5,500, MST = 8.8 mo), patients with concurrent TRT-systemic treatments (within 30 days of systemic therapy) had significantly worse OS (n = 20,099, MST = 7.2 mo, P < 0.001), while patients receiving TRT after systemic therapy had the best OS (n = 6,064, MST = 11.2 mo, P < 0.001). In 4,639 patients treated with immune therapy, TRT was associated with significantly worse OS (n = 512, MST = 11.1 mo, P < 0.001), comparing to immune therapy alone (n = 4,127, MST = 14.1 mo). Patients received concurrent TRT had worst OS (n = 177, MST = 7.4 mo, P < 0.001), comparing to TRT before immune therapy (n = 165, MST = 12.2 mo) and TRT after immune therapy (n = 138, MST = 13.2 mo, P = 0.086). Conclusions: In patients with stage IV NSCLC, TRT seemed to be associated with better OS in those treated with non-immune systemic therapy but worse overall survival in patients receiving immune therapy. Concurrent TRT with any systemic therapy including immune therapy was associated with worse survival.
Financial impact of flat dosed (FD) monoclonal antibodies (MABs) at a single institution in 2016.
Authors: Michael P. Kane, Ann W. Silk, Fuwing Lee, Paul Auriemma, Janice M. Mehnert
Journal: Journal of Clinical Oncology (2017)

6617 Background: Immuno-oncology (I/0) agents represent an important, accelerated breakthrough in cancer therapy. Like other MABs, these agents have been adjusted after FDA approval to have a flat-dose. Purportedly, flat dosing simplifies prescribing, dispensing, inventory and billing. Nivolumab (N) and Pembrolizumab (P) achieved FDA approval in several malignancies. Original studies determined the dosing of N @ 3 mg/kg q2-weeks and P @ 2 mg/kg q3-weeks. Based on simulations from population pharmacokinetics models, the FDA approved a FD of N 240 mg in melanoma, RCC and NSCLC. The financial impact of this FD methodology in our patient population was compared with weight based dosing (3mg/kg) of N with a cap of 240 mg versus flat dosing. The potential impact of this change was also evaluated for P, including if a 50 mg vial of P was still available. Methods: Applicable dispensed doses (N &amp; P) and patients’ weights for 2016 were mined from the electronic health record. Wholesale Acquisition Costs at end of year were used for financial comparison. Results: see table. Conclusions: Weight based dosing with a cap (N 240mg; P 200mg) versus flat dosing would have saved $198,567 and $80,037, respectively. Additionally, $760,351 would have been saved if 50 mg vials of P were available. With the current drug pricing structure, wide-scale adoption of flat dosing for I/O mABs may result in higher drug costs. Labeling I/O mABs with both weight-based and FD options and ensuring the availability of proper vial sizes, particularly multi-dose vials, to fit the population and dosing schema would restrain the costs of care. [Table: see text]
Cell free (cf) DNA as a tumor marker in transitional cell cancer (TCC): Monitoring response to checkpoint inhibitor (CPI) therapy.
Authors: Nicholas J. Vogelzang, Mohamed Azab, Yen Cao, Subhikshya Tiwari, Mohamad Mubder
Journal: Journal of Clinical Oncology (2018)

e16522 Background: CPI induces long term response in ~25% of patients (pts). Assessment of response is challenging given the nuances of radiographic findings. cfDNA (Guardant 360) appears to correlate with tumor burden (GUASCO 2018) and thus has potential as a tumor marker in TCC, particularly in regards to determining complete response (CR) after CPI. We hypothesized that cfDNA can serve as a marker of CR in such Methods: cfDNA percent somatic alteration burden (%SAB) and associated somatic alterations were measured by GUARDANT360 and compared with corresponding radiographic and clinical findings. cfDNA was collected at irregular intervals corresponding to clinical inflection points. Results: Between 6/2015-2/2018 197 solid tumor pts had cfDNA testing in a single practice. 62 had TCC and 21 (14:7 M:F, median age 63) received CPI with cfDNA monitoring. 72 assays (range 1-7/pt) were measured for up to 28 mos (range 2-28 mos). 16pts are alive and being monitored; 5 have died. 7 of the 62 are beginning CPI and cfDNA monitoring but are too early to evaluate. 9 the 21 CPI treated pts are in clinical CR or near CR (residual radiographic abnormalities of uncertain significance) and are off CPI for 5+ mos. The other 11 have relapsed or died. The most recent %SAB in the 9 CR pts was not detectable (ND) in 4, 0.1% in 1, 0.2% in 2,0.7% in 1 and 4.5% in 1. This pt had a nadir cfDNA of 0.8% at time of CR which rose over the ensuing yr to 4.5% when radiographic relapse occurred in 2/2018. Conclusions: cfDNA levels at 0.2% or less appear to correlate with radiographic and clinical CR to CPI. Longer follow-up and further prospective studies with larger sample sizes are needed to confirm the hypothesis that cfDNA can serve as a marker of molecular CR in TCC pts treated with CPI.