tbuckley/cabot-search huggingface dataset:
Synergism of gambogenic acid with bortezomib induce apoptosis of multiple myeloma.
Authors: Runzhe Chen, Hongming Zhang, Ping Liu, Xue Wu, Baoan Chen
Journal: Journal of Clinical Oncology (2017)

8035 Background: Multiple myeloma (MM) is one of the most common primary tumors of the bone marrow that accounts for approximately 10% of all hematological cancer. Gambogenic acid (GNA) is one of the natural compound isolated from gamboge and has demonstrated advantages such as a more potent anticancer effect and less systemic toxicity according to early investigations. In this study, we hypothesized that GNA could synergistically potentiate BTZ-induced apoptosis of MM cells and that combining BTZ and GNA may provide a more effective approach to treat MM. Methods: CCK-8 assay, CI isobologram, flow cytometry, western blot, xenograft tumour models, TUNEL and immunochemistry were used in this study to detect to possible mechanisms of apoptosis led by GNA and BTZ in vitro and in vivo. Results: The percentage of MM.1S in G2/M phase after 48h of 4.0nM BTZ, 0.90μM GNA and combination treatment were 31.09±2.16%, 26.68±1.96% and 19.88±1.89% respectively. The percentage of MM.1S in G2/M phase of control group was 17.23±1.65%. The apoptosis rates of MM.1S cells for 48h were 6.57±0.15% in control group, 89.67±5.15% after treatment with 4.0nM BTZ, 97.80±0.81% after treatment with 0.90μM GNA, and 98.9±3.86% after treatment with 4.0nM BTZ plus 0.9μM GNA respectively. All the treatment groups showed a more significant apoptosis rate compared to that of the control group ( p&lt;0.01). MM.1S tumors were implanted in BALB/Ca nu/nu male mice. The tumor weights of GNA and BTZ plus GNA groups decreased significantly when compared with those of control group (p&lt;0.01 and p&lt;0.001, respectively) and the tumor weight of combination group was significantly less than that of BTZ or GNA group (p&lt;0.001). When mice were treated with BTZ combined with GNA, the tumor inhibition rate was 41.94%, whereas those of mice treated with BTZ or GNA alone were 9.68% and 19.35%, respectively. We also found that the combined treatment could induce more markedly increased apoptosis of MM.1S cells via the activation of PARP cleavage, P53, Caspase-3 cleavage and Bax and inhibition of Bcl-2 expression. Conclusions: Our data support that a synergistic antitumor activity exists between BTZ and GNA, and provide a rationale for successful utilization of dual BTZ and GNA in MM chemotherapy in the future.
Central line-associated complications during treatment with DA-R-EPOCH therapy for NHL.
Authors: Rachel Julie David, Andrea Baran, Jennifer Kelly, Patrick Michael Reagan, Carla Casulo, Paul M. Barr, Jonathan W. Friedberg
Journal: Journal of Clinical Oncology (2017)

7543 Background: Certain non-Hodgkin lymphomas (NHL) such as primary mediastinal B-cell, Burkitt’s, and high-grade B-cell lymphoma with MYC and BCL2 rearrangements are often treated with infusional dose-adjusted rituximab, etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (DA-R-EPOCH), which requires a central line. We have observed meaningful line-associated complications (LAC) in patients (pts) treated with DA-R-EPOCH. With the ongoing use of this regimen, we sought to identify the rates and correlates of LAC in this population. Methods: We retrospectively identified all pts treated with DA-R-EPOCH at the Wilmot Cancer Institute between 3/2011 and 10/2015. Our primary endpoint was the rate of LAC, including venous thromboembolism (VTE), extravasation, and line-associated infection (LAI) diagnosed during DA-R-EPOCH therapy. Our secondary endpoint was the rate of VTE during therapy. Rates and 95% confidence intervals (95% CI) were calculated for all endpoints. Univariate logistic regression was used to calculate odds ratios to evaluate potential predictors. Results: 43 pts received DA-R-EPOCH during the study period. 70% of pts were male; median age was 52 years. 17 pts (39.5%, 95% CI 0.25 - 0.56) experienced at least 1 LAC: 15 pts (35%, 95% CI 0.21 - 0.51) had VTE; 3 pts had LAI; and 2 pts experienced extravasations. Grade 3 toxicity was seen in 41% (7/17): 4 pts with VTE, and 3 pts with LAI. Both extravasation events were grade 2, and both occurred with mediports. In univariate analysis, BMI ≥ 35 kg/m² and receiving therapy via peripherally inserted central catheter (PICC) line were significantly associated with an increased risk of VTE (p=0.04 and p=0.02, respectively). Conclusions: 40% of pts receiving DA-R-EPOCH therapy for treatment of NHL developed LAC, almost half of whom experienced grade 3 toxicities. Clinicians need to balance these risks when selecting therapy, particularly with the lack of randomized data to support the DA-R-EPOCH approach in many circumstances. Given observed extravasations, we avoid mediports in favor of PICC lines, however this approach carries a significant risk of VTE. Future studies are needed to evaluate the role of prophylactic anticoagulation in this population.
Evaluation of carboplatin toxicities and efficacy using different body weight descriptors in the Calvert formula.
Authors: Tulip A Jhaveri, Brigitte Gil, Mei Zou, Nathan Hartwell, Jacob Sands
Journal: Journal of Clinical Oncology (2017)

e14017 Background: Carboplatin dosing is calculated using the Calvert formula that includes glomerular filtration rate (GFR). In practice, GFR is often substituted by creatinine clearance (CrCl) with the Cockcroft-Gault (CG) equation. However, there is no standardization of which body weight descriptors should be utilized. Data suggest use of total body weight (TBW) may overestimate CrCl in overweight patients, while adjusted body weight may better estimate CrCl. The primary objective is to determine the impact of using different weight descriptors (DWD) in place of TBW for carboplatin dosing. Methods: This was a single-center, retrospective cohort study. Patients over 18 who were intended to receive at least 6 cycles of carboplatin with target area under the curve (AUC) of 5 or 6 and paclitaxel 175 to 225 mg/m 2 were included. DWD included: adjusted body weight for overweight and obese patients, ideal body weight for normal weight patients and TBW for underweight patients. Primary endpoint was the composite of grade 3 or 4 anemia, thrombocytopenia and neutropenia (hematologic toxicity). Secondary endpoints included individual parameters of the primary endpoint, dose delays, dose reductions, progression-free survival, overall survival and objective response rate. Results: A total of 117 patients were included (DWD: n = 39; TBW: n = 78). Results on survival analysis, anemia and dose reductions are pending. Conclusions: To our knowledge, this is the first evaluation of patient outcomes specifically comparing carboplatin dosing calculations. Although there is a trend toward decreased grade 3 and 4 hematologic toxicities in the DWD group, there is no statistically significant difference in this under powered cohort. However, there was a significant decrease in treatment delays and days of treatment delay (p &lt; 0.001) in the DWD group. Further studies are needed to evaluate the impact of DWD on carboplatin dosing. [Table: see text]
Testing a behavioral intervention to improve adherence to adjuvant endocrine therapy (AET).
Authors: Gretchen Genevieve Kimmick, Hayden B Bosworth, Francis J Keefe, Linda Sutton, Lynda Owen, Alaattin Erkanli, Shelby D. Reed, Sarah A Staley, Sarah Pak, Nadine Barrett, Scott Huettel, Rebecca A. Shelby
Journal: Journal of Clinical Oncology (2017)

TPS10128 Background: Adjuvant endocrine therapy (AET) is a crucial component of treatment used to prevent recurrence and reduce mortality for women with hormone receptor positive breast cancer. Poor adherence to AET is a significant problem, with rates of non-adherence ranging from 28% to 59%. Non-adherence to AET contributes to increased medical costs and increased mortality. Symptoms (e.g., pain, hot flashes, sleep problems, vaginal dryness) associated with AET are related to non-adherence and early discontinuation of treatment. Our goal is to test the efficacy of a novel self-management intervention (SMAET) that teaches patients skills for enhancing adherence to AET and coping with AET-related symptoms. Methods: Trial participants will be recruited from a tertiary care medical center and community clinics that are located in medically underserved areas. Target enrollment is 400 patients. Prospective participants must meet the following criteria: diagnosis of Stage I to III breast cancer; hormone receptor positive tumor; local definitive cancer treatment complete; within 12 months of beginning AET; have at least 18 months of AET recommended; and at least 21 years of age. We will test the effects of the SMAET intervention (n = 200) by comparing it to a general health education intervention (n = 200; attention control). The SMAET protocol includes 7 sessions providing systematic training in coping skills for managing symptoms that interfere with adherence and 3 maintenance calls delivered over 6 months by a nurse via the phone. The intervention also includes interactive voice messaging that is tailored based on real-time adherence data. The primary study outcome, adherence to AET, will be assessed in real-time for 18 months using wireless smart pill bottles (i.e., bottle opening and percent of pills remaining). Symptom interference will be examined as a secondary outcome and will be assessed over 18 months. If effective, the intervention may reduce the burden of AET use. Clinical trial information: NCT02707471.
A prospective, randomized, double-blinded, placebo-controlled, phase III study to evaluate the efficacy and safety of apatinib plus best supportive care (BSC) compared to placebo plus BSC in patients with advanced or metastatic gastric cancer: The ANGEL study.
Authors: Yoon-Koo Kang, Narikazu Boku, Won Ki Kang, Harry H. Yoon, Stefano Cascinu, Salah-Eddin Al-Batran, Scott Houston, Cheol Hee Park, Arlo N. McGinn, Ian Chau
Journal: Journal of Clinical Oncology (2017)

TPS4138 Background: Apatinib is an orally administered, highly selective tyrosine kinase inhibitor of VEGFR-2 that has been studied in many clinical trials, primarily in China, treating various solid tumors. Based on the results of the Chinese Phase 3 study, apatinib was approved in China for the treatment of advanced gastric cancer (GC), but apatinib has yet to be evaluated in a randomized placebo-controlled study in the rest of the world. ANGEL is a multinational, placebo controlled, Phase 3 study investigating the efficacy and safety of apatinib in advanced GC patients in North America, Europe, and Asia Pacific. Methods: Main eligibility criteria include patients with advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction for whom at least 2 prior lines of standard chemotherapy had failed, ECOG performance status ≤ 1, and disease progression &lt; 6 months after last chemotherapy treatment. Approximately 459 patients will be randomized in a 2:1 ratio to receive continuous 28-day cycles of apatinib 700 mg or a matched placebo daily with best supportive care until disease progression, intolerable toxicity or withdrawal of consent. Stratification factors include geographic region (Asia vs. North America/Europe), disease measurability, prior ramucirumab treatment, and treatment therapy line (3 rd or 4 th ). Primary endpoint is overall survival (OS) in the intent-to-treat population, and secondary endpoints are progression free survival (PFS), objective response rate (ORR), disease control rate (DCR), quality of life, and safety. The primary analysis of OS will be conducted in intention-to-treat population using a stratified log-rank test at the two-sided alpha = 0.05 level of significance. If the primary analysis of OS is statistically significant, then PFS and ORR will be analyzed. All other secondary efficacy endpoints will be analyzed using two-sided tests at the alpha = 0.05 level of significance. Enrollment opened Feb 2017. Clinical trial information: NCT03042611.
TCT-863 SCOUT 1 Trial: Impact of Center Experience on Intraprocedural and 30 Day Outcomes
Authors: Charles Davidson, Christopher Meduri, Rebecca Hahn, Mark Ricciardi, Scott Lim, None Vivek Rajagopal, Tamim Nazif, Gorav Ailawadi, Susheel Kodali
Journal: Journal of the American College of Cardiology (2018)
A randomized phase II study of perioperative chemotherapy plus bevacizumab versus postoperative chemotherapy plus bevacizumab inpatients with upfront resectable hepatic colorectal metastases (APPROACH).
Authors: You Jin Chun, Seong-Geun Kim, Keun-Wook Lee, Sang Hee Cho, Tae Won Kim, Ji Yeon Baek, Young Suk Park, Soojung Hong, Jee Hung Kim, Seung-Hoon Beom, Minkyu Jung, Sang Joon Shin, Joong Bae Ahn
Journal: Journal of Clinical Oncology (2018)

3528 Background: Whether patients with resectable colorectal cancer liver metastases (CRLM) gain a survival benefit or not from neoadjuvant chemotherapy remains controversial. The addition of bevacizumab to chemotherapy also remains unclear. Methods: 76 patients with CRLM were randomly assigned to either six cycles of FOLFOX or FOLFIRI with bevacizumab before and six cycles after surgery or to twelve cycles after surgery. The primary objective was to detect DFS. The primary analysis was by intention to treat and DFS were estimated by the Kaplan-Meier method and compared by the log-rank test. This trial was registered with ClinicalTrials.gov, number NCT01632722. Results: In patients with chemotherapy plus bevacizumab, the median DFS was 37.4 months at 5.4 years follow-up and the median overall survival (OS) was not reached. The DFS between the perioperative group and the postoperative group showed a better tendency in the perioperative group, but there was no statistical difference (HR 0.837 [95.0% CI 0.606-1.156], p = 0.280). The OS was statistically better in the perioperative group (p = 0.049). There was no difference in DFS between the two groups in patients with CEA≥5 or more than two liver metastases, but there was OS benefit in the perioperative group than in the postoperative group (CEA, HR 0.485 [95.0% CI 0.252-0.933], p = 0.030; number of liver metastases, HR 0.548 [95.0% CI 0.300-0.999], p = 0.049). BMI, the largest size of liver metastases, primary T or N stage, disease-free interval, and sidedness did not affect the difference in DFS and OS. There was no difference in postoperative complications of bevacizumab and adverse event during chemotherapy between the two groups. Conclusions: In patients with resectable CRLM, perioperative chemotherapy had no effect on DFS but improved OS. The perioperative chemotherapy plus bevacizumab do not increase the risk of complications in liver resection. Patients with high levels of CEA or the number of liver metastases may have benefited from perioperative chemotherapy. Clinical trial information: NCT01632722.
Should surveillance guidelines be different based on Human Papilloma Virus (HPV) status? Patterns of failure and second primary cancers (SPM) in patients (pts) with oropharyngeal squamous cell cancer (OPSCC).
Authors: Ryan Holstead, Anusha Vege, Keara M. Barnaby, Doru Paul, Steven R. Savona, Priscila Hermont Goncalves, Douglas K. Frank, Dev Kamdar, Lucio Pereira, John Fantasia, Maged Ghaly, Jed Michael Pollack, Sewit Teckie, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2018)

e18059 Background: HPV pos OPSCC is clinically and biologically distinct from tobacco/alcohol-related cancer. HPV-positive (pos) tumors have favorable prognosis and respond better to treatment. Studies suggest that pattern of failure differs between HPV-negative (neg) and pos cohorts with loco-regional failure (LRF) being more common with former and distant metastases (DM) with latter. Pts with alcohol/tobacco exposure have increased incidence of SPM in head and neck (HN) or lung due to field cancerization. However, the incidence and sites SPM in pts with HPV pos OPSCC are not well-characterized. Methods: Charts of pts with OPSCC diagnosed between 2012 and 2014 with minimum follow up of 2 years were reviewed. Differences in rate and pattern of synchronous and metachronous SPM as well as recurrent/persistent disease (failure) in HPV pos and neg OPSCC were assessed. Descriptive statistics was used to summarize the data. Results: 157 pts were included. There was male predominance (78%) and median age was 60 years. Common primary sites were base of tongue (64), and tonsil (76). Most pts had advanced disease- 96 with stage IVA/B and 23 with stage III (AJCC 7th). 132 pts were HPV pos and 25 HPV neg. Majority of pts (80.3%) received definitive chemoradiation. Failure was noted in 23 HPV pos (15.15%) and 12 HPV neg pts (40.0%%) [OR 0.229, CI 0.093-0.565, P = 0.001]. 5/23 (22%) of failures in HPV pos were DM, 2 of which were non-pulmonary compared to 2/12 (16.7%) pts in the HPV neg group both of which included lung metastases. 27 HPV pos pts (20.5%) and 8 HPV neg (32.0%) had SPM [OR 0.546, CI 0.213-1.40, P = 0.208 ]. 7/8 SPM (87.5%) in HPV neg group and only 2/27 (7.4%) in HPV pos were of HN or lung [OR 0.011 CI 0.001-0.145, P < 0.001]. 25 HPV pos pts had SPM at other sites, specifically skin, hematologic, thyroid, renal and cervical. Conclusions: Incidence of relapse, patterns of failure and SPM differ in HPV-pos and neg OPSCC. Unlike in the HPV neg group, HPV pos failures and SPM often occur in sites other than HN/lung. These observations may have implications for disease surveillance and should be validated in larger, prospective studies.
Predicting response to radical (chemo)radiotherapy (R-CRT) with circulating HPV DNA and tumor DNA (ctDNA) analysis in locally-advanced head and neck squamous cell carcinoma (LAHNC).
Authors: Shreerang Bhide, Jen Lee, Isaac Garcia-Murillas, Ros Cutts, Tara Hurley, Lorna Grove, Christopher Nutting, Kate Newbold, Nicholas C. Turner, Kevin Harrington
Journal: Journal of Clinical Oncology (2017)

6043 Background: Following R-CRT for human papilloma virus positive (HPV+) and negative (HPV-) LAHNC, patients frequently undergo unnecessary neck dissection (ND) and/or repeated biopsies for abnormal PET-CT findings even in the presence of a complete pathological response (pCR), which causes significant morbidity. We assessed the role of circulating tumor DNA analysis in identifying patients with true residual disease. Methods: We prospectively recruited development (DC, n=55) and test (TC, n=33) cohorts of LAHNC patients having R-CRT. For HPV+ tumors we developed a novel amplicon based next generation sequencing assay (HPV-detect) to detect circulating HPV DNA and for HPV- tumors we used personalised droplet digital PCR assays of somatic mutations. Circulating tumor DNA levels at 12 weeks post-R-CRT were correlated to residual disease assessed by PET-CT and surgery. Results: In the DC (27 HPV+), baseline HPV-detect demonstrated 100% sensitivity and 93% specificity, confirmed in the TC (20 HPV+). 37 HPV+ patients (DC&amp;TC) had complete samples-set. 36 had a negative HPV-detect at end of treatment, including 6 patients who underwent ND (3) and repeat primary site biopsies (3) for positive PET-CT but had pCR on surgical/biopsy specimen. 1 patient had positive HPV-detect and positive biopsy, indicating 100% agreement for HPV-detect and residual cancer. In a 10 HPV- patients with complete sample-set, there was 90% agreement between ctDNA and residual disease in HPV- tumors (3 ctDNA positive and tumor present, 1 ctDNA negative but tumor present, and 6 negative ctDNA negative tumor) with 80% sensitivity for residual disease and 100% specificity. Combined agreement between ctDNA testing (HPV+ and -) &amp; residual disease was 98% (Table). Conclusions: Circulating HPV DNA quantified using HPV-detect and ctDNA identifies patients with residual disease post-R-CRT in LAHNC. Further studies are required to validate these findings. [Table: see text]
Quality of life as a predictor of early death in older cancer patients: A prospective cohort study.
Authors: Jurema Telles O Lima, Luiz Claudio Santos Thuler, Anke Bergmann, Barbara laffayette viana da Luz, Maria Julia Gonçalves Mello
Journal: Journal of Clinical Oncology (2018)

e22017 Background: Aging is the major risk factor for cancer. Health-related Quality of Life (HRQoL) is an important aspect to be studied in the elderly population with cancer, not only as an end-point, but also as a predictive factor of survival and in guiding care. Methods: Prospective cohort study. 608 elderly cancer patients (≥ 60 years old) were followed for 6 months. Clinical variables were collected. HRQoL at cancer diagnosis was considered as exposure and was assessed through the EORTC QLQ C30 questionnaire. The outcome was death occurred in the first six months. Descriptive analysis was performed for continuous variables, and absolute and relative frequencies for categorical variables. Student t test was used to compare the mean scores of the domains of quality of life among those who progressed or not to early death. Univariate (unadjusted) and multiple logistic regression (adjusted for clinical staging and age) between HRQoL and occurrence of early death were performed. Results: The 608 elderly cancer patients had mean age of 71.9 years (SD 7.4), and 50.7% were male. Prostate cancer was the most frequent type of cancer (29.1%). Metastatic disease at cancer diagnosis were observed in 29.3% of the patients and were at risk of malnutrition, 50.2%. During the follow-up period, there were 100 deaths (16.4%). After adjusting for cancer stage and age, a one-point improvement in the global health status and physical functioning corresponded to a 2% reduction in the risk of early death (OR = 0.98). For role, cognitive, emotional and social functioning the reduction in risk of death was 1% (OR = 0.99). Regarding the symptoms scales, the increase of one point in the score reflects an increased risk of early death of 1% for pain, insomnia and nausea/vomiting (OR = 1.1) and 2% for fatigue and dyspnoea (OR = 1.02). Conclusions: For all functional scales and global health status, worse scores were found among those who died prematurely. Worse quality of life on the scales of symptoms was also observed among those with early death, except for diarrhoea. HRQoL at cancer diagnosis is a good predictor of early mortality in elderly cancer patients.