tbuckley/cabot-search huggingface dataset:
Safety of Topical Calcineurin Inhibitors for Hailey-Hailey Disease
Authors: Fei Han
Journal: JAMA (2018)

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Prognostic and predictive blood-based biomarkers (BMs) in patients (pts) with advanced epithelial ovarian cancer (EOC) treated with carboplatin–paclitaxel (CP) ± bevacizumab (BEV): Results from GOG-0218.
Authors: Angeles Alvarez Secord, David Tritchler, Yingmiao Liu, Mark D. Starr, John C. Brady, Heather A. Lankes, Herbert Hurwitz, Robert S. Mannel, Krishnansu Sujata Tewari, David M. O'Malley, Heidi J. Gray, Jamie Nadine Bakkum-Gamez, Keiichi Fujiwara, Matthew Boente, Wei Deng, Robert Allen Burger, Michael J. Birrer, Andrew B. Nixon
Journal: Journal of Clinical Oncology (2016)

5521 Background: GOG-0218, a double-blind placebo (PLA) controlled phase III trial of 1873 pts with advanced EOC, compared CP with either PLA (CPP), BEV 15 mg/kg q3w → PLA (CPB15), or BEV 15 mg/kg q3w → BEV for 15 mo (CPB15+). Study results demonstrated significantly improved progression-free survival (PFS), but no overall survival (OS) benefit with BEV. Blood samples were collected for BM analyses. Methods: Plasma samples were analyzed via multiplex ELISA technology for 5 pre-specified candidate BMs (IL6, Ang-2, osteopontin (OPN), stromal cell-derived factor-1 (SDF-1), and VEGF-D). Associations of BMs' baseline values with PFS and OS were assessed as continuous variables using multivariate Cox proportional hazard regression models including the covariates age, stage, debulking status and performance status. Predictive markers were identified using treatment by marker interaction term in multivariate Cox models. Results: Baseline samples were available from 752 pts. According to our pre-specified analysis plan, IL6 was strongly predictive of a therapeutic advantage with BEV for both PFS and OS. Pts with high IL6 levels treated with BEV had longer PFS (14.2 vs. 8.7 mo) and OS (39.6 vs. 33.3 mo) compared to PLA. Increasing IL6 levels were associated with greater benefit from BEV. For PFS: Low IL6, HR 0.87 [CI 0.70-1.08]; Median, HR 0.77 [CI 0.58–1.01]; High, HR 0.67 [CI 0.48–0.94]; interaction p=0.009; for OS: Low IL6, HR 1.07 [CI 0.84–1.37]; Median, HR 0.92 [CI 0.67–1.26]; and High, HR 0.79 [CI 0.54–1.16]; interaction p=0.005. Additionally, both IL6 and OPN were found to be negative prognostic markers for both PFS and OS (p<0.001). No predictive associations were seen for other BMs tested. Conclusions: The inflammatory cytokine IL6 is highly predictive of therapeutic benefit from BEV when combined with CP. Plasma IL6 may define those EOC pts more or less likely to benefit from the addition of BEV to standard chemotherapy. These data are consistent with previous findings in which IL6 predicted benefit from BEV and pazopanib in renal cell cancer, highlighting the importance of inflammation in ovarian and renal cancers.
Intervention programs to improve oral chemotherapy safety and quality.
Authors: Benjamin Adam Goldenberg, Jessica A. Zerillo, Ritesh R. Kotecha, Alok K Tewari, Joseph O. Jacobson, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2016)

e18220 Title: Intervention Programs to Improve Oral Chemotherapy Safety and Quality Background: With the growing use of oral chemotherapy, there is an urgent need to develop safe and effective systems to administer and manage these agents. A comprehensive synthesis of available literature on oral chemotherapy administration and management programs to which clinicians and policy makers can look for best practices is lacking. Methods: We performed a systematic review of MEDLINE/PubMed, EMBASE, CINAHL, and the grey literature to identify oral chemotherapy administration and management intervention programs. Our population of interest included all ages and was limited to traditional cytotoxic as well as targeted anti-cancer oral agents. Interventions were evaluated in the categories of prescribing, dispensing, education and monitoring. Results: From 8,571 abstracts identified in the peer-reviewed literature, 31 were selected for further full text review with an additional 7 abstracts identified in the grey literature. Of those abstracts, 12 full text articles met inclusion criteria. Of these full text articles, 11 were in adult and 1 was in pediatric oncology. 1 focused on interventions in prescribing; 4 in dispensing; 8 in education, and 4 in monitoring. 5 reported clinical, safety and toxicity outcomes whereas 7 reported adherence outcomes. Of the clinician led interventions, 5 were conducted by clinical pharmacists and 4 by nursing teams; none documented physician-led interventions. Conclusions: There is a paucity of data in the peer-reviewed and grey literature in this area. In the few studies that showed successful program implementation, pharmacists and nurses played key roles in leading the interventions. More formal research on such programs is needed in order to analyze the effectiveness of oral chemotherapy management interventions and establish best practices.
Analysis of inflammatory signatures of cancer spheroids in blood and their role in metastasis.
Authors: Peter Geck, Viktoria Denes, Bálint Tegze, Laszlo Graf, Gabor Barna, Andrea Naphegyi, Andrew Makarovskiy
Journal: Journal of Clinical Oncology (2018)

3090 Background: Cancer mortality correlates with metastatic progression where genetic/epigenetic changes in the cancer are important. Recent data indicate, however, that the host thrombotic and inflammation responses are also critical in the metastatic process, but not well understood. We performed exploratory observational studies by filter-capturing cancer spheroids/clusters in blood and studied inflammatory signatures. We investigated the hypothesis that thrombotic/inflammatory factors can stabilize circulating cancer stem cell clusters and critical in metastasis. Methods: Cancer spheroids were collected from the blood of 25 metastatic patients (clinically verified metastasis; > 6 months post-treatment) and 25 samples from controls. Gene expression studies in the spheroids targeted EpCAM (epithelial cancer origin); SOX2, NANOG and OCT4 (stem cells); platelet specific selectin (Sel-P) and CD41; IL1beta (innate immunity/inflammatory signature); and PD-L1 (tumor immunity) markers. Poisson regression with overdispersion and the NCSS/PASS package was used for statistical calculations. Results: Flow cytometry detected cancer spheroids in 60 % of metastatic blood samples, while only 5 % in primary non-metastatic samples. Filtration collected circulating cancer stem cell spheroids in 72.7 % of metastatic patients and a striking 95.5 % of them showed markers for immune/inflammatory response. In contrast, filtration found circulating cancer stem cell spheroids in only 15.8 % of the non-metastatic samples and only 5.2% showed immune/inflammation response. On the other hand, 90 % of the primary cancer patients were positive for non-cancer related thrombo-embolic micro-clusters (epithelial negative). As it was not found in healthy controls, it may indicate upregulated innate immunity as early as the primary cancer Conclusions: The findings support our previous results that circulating cancer spheroids may disseminate metastasis and suggest that innate immunity/inflammation is critical to stabilize cancer stem cell spheroids in circulation. The new inflammation checkpoint in metastatic progression raises the possibility of anti-inflammation modalities to prevent metastasis.
Comprehensive profiling of biliary tract cancers (BTC) to reveal molecular heterogeneity with implications for matched targeted therapies (MTT).
Authors: Tamara Sauri, Teresa Macarulla, Guadalupe Cabrera, Helena Verdaguer, Fiorella Ruiz, Ana Vivancos, Jaume Capdevila, Elena Elez, Maria Alsina, Guillem Argiles, Cinta Hierro, Julieta Grasselli, Ignacio Matos, Jordi Rodón, Paolo Nuciforo, Rodrigo Dienstmann, Josep Tabernero
Journal: Journal of Clinical Oncology (2016)

4085 Background: BTC is an heterogeneous disease that includes intrahepatic cholangiocarcinoma (IHC), extrahepatic cholangiocarcinoma (EHC), gallbladder carcinomas (GBC) and ampulloma (AM), typically present an advanced stage at diagnosis and chemotherapy (chemo) has limited efficacy. We describe potentially targetable genomic alterations (ptGA) of BTC and impact of MTT in these patients (pts). Methods: From 2011 to 2015, 104 chemorefractory patients (pts) with BTC (62 IHC, 23 EHC, 15 GBC, 4 AM) were referred to molecular profiling at our institution. Archived tumor samples were analyzed using different panels (FoundationOne in 27, Amplicon-MiSeq in 25, MassARRAY-Sequenom in 23, Fusion-Nanostring in 31 and protein expression in 13) and pts were offered MTT in Phase 1 trials according to specific eligibility criteria and logistics. Results: Median age was 57 y (27-82); metastatic sites were liver (81%), nodes (43%) and lung (21%); median time to progression on first-line chemo was 5.1 months (m) (CI95% 4.1-6.3); 27% received 2 or more chemo lines. At least one ptGA was detected in 49% of the samples, with proportional increase according to the size and spectrum of gene alterations tested (p<0.001). Type of ptGA differed across tumor types (see Table). Additional ptGA in IHC (BRAF D594, ERBB2 S310, RNF43 and BRCA2 mut) and EHC (BRAF G469 and ERBB2 S310 mut) were found in single cases. A total of 22 pts were enrolled in Phase 1 trials, 13 of them with a direct MTT (5 PI3K, 2 MEK, 2 MET, 2 IDH1, 1 ERBB2 and 1 FGFR inhibitor [inh]). Partial response was observed in 1 case (MET ampl IHC with MET inh) and prolonged stable disease in 3 pts (1 FGFR2 fusion IHC with FGFR inh; 1 IDH1 mut IHC with IDH1 inh; 1 NRAS mut GBC with MEK inh). Conclusions: The diverse landscape of ptGA in BTC is a rich source for MTT in early clinical trials, and has the potential to improve outcomes of individual pts. Expanding gene panels to identify these driver alterations (mut, ampl and fusions) is key for precision medicine in BTC. IHC (n=62) EHC (n=23) GBC (n=15) AM (n=4) IDH1 mutation [mut] 18% 6% 10% - IDH2 mut 9% - - - FGFR2 fusion 7% - - - ERBB2 amplification [ampl] - 12% 80% - PIK3CA mut 4% 6% 30% - RAS mut 13% 24% 10% 67% MET ampl 11% - - -
A survey of perceptions of healthcare workers on the cost and safety of oral oncolytic agents in practice.
Authors: Madeline Tompkinson, Kelly Fine, Dean Gruber, Ivo Abraham, Hani M. Babiker, Ali McBride
Journal: Journal of Clinical Oncology (2018)

e18926 Background: The number of newly approved agents in the U.S. Healthcare System continues to increase with over 800 new oncology agents in the pipeline and 25% of these being oral agents. Oral chemotherapy agents have several advantages including patient convenience, prolonged drug exposure, and non-invasive administration. These advantages come at a premium that many patients cannot afford leading to change or abandonment. Methods: This is a descriptive, non-experimental, cross-sectional study of healthcare professionals including pharmacists, physicians, advanced practitioners, nurses, pharmacy administrators, or others in hematology/oncology patient care across the United States. Data was collected using a 35-item online questionnaire to measure quality improvement areas when using oral chemotherapy agents. Results: Results of 503 survey respondents comprised of pharmacists (54%), physicians (5%), advanced practitioners (4%), nurses (10%), pharmacy administrators (15%), social workers (2%), and other professionals (9%). Treatment abandonment due to cost is seen by 46.6% of respondents. The most common agents abandoned due to cost included capecitabine, abiraterone, and palbociclib. Prior authorization delays occur in 1-2 patients weekly creating a 4-6 day wait to initiate therapy and 24.0% of respondents spend more than 30 hours weekly resolving these issues. Respondents reported 1-2 patients every 6 months requiring a change of therapy due to insurance denial. Adjudication under the Oral Chemotherapy Parity Law was utilized by 12.4% of respondents, 27.7% did not adjudicate, and 59.9% did not know. The most utilized medication assistance programs include Manufacturer Assistance Programs, Disease-Based Foundations, and Manufacturer Co-Pay Cards. Conclusions: Results from healthcare workers indicate a high incidence in abandonment of therapy, delay in therapy initiation, and significant resources allocated to issues associated with the cost of oral chemotherapy agents. Further evaluation is required to resolve issues in therapy and minimize impact on patient care. Future objectives should include improving adherence and overall survival of oral chemotherapy patients.
Phase II trial of S-1 and concurrent radiotherapy (RT) in elderly patients (pts) with esophageal squamous cell carcinoma (ESCC).
Authors: Tao Song, Min Fang, Shiliang Lv, Yongshi Jia
Journal: Journal of Clinical Oncology (2018)

e22018 Background: The management of elderly ESCC patients remains a therapeutic challenge. The aim of this phase II trial was to evaluated the efficacy and safety of chemoradiotherapy (CRT) comprising a single S-1 based chemotherapy agent combined with RT in elderly ESCC patients. Methods: From 01/2016 till 09/2017, patients aged 70 years and older were prospectively treated with intensity modulated RT (IMRT) combined with S-1. Other selection criteria included ECOG PS 0-1, disease stage I-IVa, an adequate biological profile and domains referred to the geriatric assessment. IMRT was delivered with a daily fraction of 1.8-2.0 Gy to a total RT dosage of 54.0-60.0 Gy. Preplanned concurrent S-1 (70 mg/m2/d) was given on days 1-14, every 3 weeks. After CRT, consolidation S-1 was repeated up to four cycles. Results: The median age of patients was 76 (range: 70-86) years, and the clinical stages were stage I (one patient), stage II (14 patients), stage III (16 patients), and stage IVa (7 patients). In the intention-to-treat analysis, thirty-one patients completed preplanned treatment with a response rate of 84.2% (95%CI: 72.1-96.4%), including twelve (31.6%) patients with complete response and 20 (52.6%) patients with partial response. At the last follow-up in Dec 2017, the estimated 1-year OS and PFS rates were 73.2% (95CI: 0.528-0.936) and 68.2% (95%CI: 0.437-0.927), respectively. Grade ≥3 leukopenia was found in 8 (21.1%) patients. The most frequent non-hematologic toxicities were esophagitis including five patients and one patient with grades 3 and 4, respectively. Conclusions: This trial achieved its prespecified endpoint with more than 80% of patients having anti-tumor response. Acute treatment-related toxicities were manageable and long-term follow-up is still required to confirm its efficacy. Clinical trial information: NCT02716688.
The impact of caregiver’s role preference on decisional conflicts and psychiatric distresses in decision making to help caregiver’s disclosure of terminal disease status.
Authors: Shin Hye Yoo, Young Ho Yun, Kyoung-Nam Kim, Jung Lim Lee, Jeanno PARK, Youn Seon Choi, Yeun Keun Lim, Samyong Kim, Hyun Sik Jeong, Jung Hun Kang, Ho-Suk Oh, Jichan Park, Si-Young Kim, Hong-Suk Song, Keun Seok Lee, Dae Seog Heo, Young Seon Hong
Journal: Journal of Clinical Oncology (2017)

10106 Background: A decision aid (DA) increases knowledge, decreases decisional conflicts and regrets and improves post-decision satisfaction, emotional distress. However, few DA trials have revealed whether decisional role preferences have an impact on patient-reported outcomes by decision making. The objective of this study was to investigate the impact of caregiver’s decisional role preference on decisional conflicts and psychiatric distresses in decision making. Methods: 406 of 444 caregivers of terminally ill cancer patients enrolled onto a previous trial determining the efficacy of the decision aid about disclosure of terminal disease status were included in this analysis. The analysis outcomes were change score of decisional conflicts using the Decision Conflict Scale (DCS) and depression and anxiety using the Hospital Anxiety and Depression Scale (HADS) at 1 and 3 months from baseline. Participants were divided into 4 groups: active caregiver who received DA (active-DA), active caregiver in control group (active-control), passive caregiver who received DA (passive-DA), and passive caregiver in control group (passive-control). Linear mixed model was conducted to find out the impact of caregiver’s decisional role preference on the DCS and the HADS. Results: Among 406 caregivers, 137 (33.7%) showed active role preference, and 269 (66.3%) showed passive role preference. In post-hoc analysis of adjusted differences of change scores between passive-DA and active-DA groups, non-significant differences were observed in DCS. However, at 3 months, change scores of HADS depression subscale increased as 4.43 (95% confidence interval (CI), 0.78-8.07; P&lt; 0.007; effect size (ES) 0.71) and those of HADS anxiety subscales increased as 4.14 (95% CI, 0.37-7.91; P= 0.021; ES 0.61) in passive-DA group than in active-DA group, showing moderate to large difference. Conclusions: These findings suggest that information about decision making might be provided with tailored format for how much individual wish to involve in decision making.
Survivorship care plans: Recommended vs delivered care.
Authors: Karen L. Smith, Talia Sobel, Kathy McGurk, Colette Magnant, Victoria Croog, Ida Vaclavik, Vered Stearns, Antonio C. Wolff, Jean Wright
Journal: Journal of Clinical Oncology (2017)

10076 Background: The Committee on Cancer set a benchmark for the provision of survivorship care plans (SCP) to ≥50% of early cancer patients by the end of 2017 despite limited data indicating benefit. One hypothesis is that SCP will reduce overuse of medical care in survivors. Methods: We performed a retrospective review of all patients with early breast cancer (BC) who were seen by a single nurse practitioner (NP) for provision of SCP after completion of primary therapy (surgery, radiation +/- chemotherapy). We evaluated adherence to recommendations for follow-up (FU) care and testing in accordance with established guidelines. Results: Between August 2013 and December 2014, 152 patients received SCP after completion of primary therapy (median 2 months, range 0-27). 98% of SCP were given to patients, but only 38% were sent to primary care providers (PCP). Median FU was 23 months. Among 130 patients who did not undergo bilateral mastectomy for whom surveillance breast imaging (SBI) was recommended, 10 (8%) had 1 st SBI ≥3 months earlier than time recommended (TR), 102 (78%) within 2 months of TR, 12 (9%) ≥3 months after TR, and 6 (5%) lacked confirmation of 1 st SBI. Among 113 in whom 2 nd SBI dates were specified, 25 (23%) had SBI ≥3 months earlier than TR, 62 (55%) within 2 months of TR, 7 (6%) ≥3 months after TR, and 18 (16%) lacked confirmation of 2 nd SBI. Among 71 patients for whom first medical oncology (MO) FU visit dates are known, 64 (90%) occurred within 3 months of TR and among 81 patients for whom first radiation oncology (RO) FU visit dates are known, 67 (83%) occurred within 3 months of TR. However, among 47 patients for whom first FU visit dates with at least 2 types of providers (MO, RO and/or surgery) are known, 15 (32%) visited 2 providers within 2 months of one other. During the 1 st year after completion of primary therapy, 22% underwent body imaging (CT, PET-CT, or bone scan) and 21% had liver function tests. Conclusions: Despite provision of a SCP to patients, PCP were often not notified and healthcare utilization exceeded recommendations. Nearly a third of patients had redundant visits, a fourth had SBI earlier than recommended, and a fifth had body imaging and lab testing. Ongoing efforts are needed to coordinate care and minimize unnecessary testing in BC survivors.
Notch signaling mediated by Delta-like ligands 1 and 4 controls the pathogenesis of chronic GVHD in mice
Authors: Vedran Radojcic, Katelyn Paz, Jooho Chung, Jing Du, Eric T. Perkey, Ryan Flynn, Sanja Ivcevic, Michael Zaiken, Ann Friedman, Minhong Yan, Maria A. Pletneva, Stefanie Sarantopoulos, Christian W. Siebel, Bruce R. Blazar, Ivan Maillard
Journal: Blood (2018)
Abstract IA11: Germline genetic testing in prostate cancer
Authors: Colin C. Pritchard
Journal: Cancer Research (2018)

Abstract Recent studies have revealed a higher than expected frequency of germline autosomal dominant cancer predisposition gene mutations in men with high-risk and advanced prostate cancer. These mutations have important implications for risk-stratification and precision therapy, as well as for cancer risks in family members. This has led to relatively rapid adoption of germline panel genetic testing in clinical practice, and facilitated identification of cancer-free men who are mutation carriers at elevated risk for prostate cancer. This talk will cover the spectrum of germline cancer predisposition genes associated with prostate cancer, issues surrounding clinical genetic panel testing, and emerging data on how germline genetic information may be used to inform screening and risk. Citation Format: Colin C. Pritchard. Germline genetic testing in prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Prostate Cancer: Advances in Basic, Translational, and Clinical Research; 2017 Dec 2-5; Orlando, Florida. Philadelphia (PA): AACR; Cancer Res 2018;78(16 Suppl):Abstract nr IA11.