tbuckley/cabot-search huggingface dataset:
MYC as a therapeutic target for the treatment of triple-negative breast cancer.
Authors: Sarah A. Foley, Alina Castell, Emma Kavanagh, Naoise C Synnott, John Crown, Lars-Gunnar Larsson, Michael J. Duffy
Journal: Journal of Clinical Oncology (2019)

e12550 Background: Despite intensive efforts, a validated targeted therapy for triple-negative breast cancer (TNBC) remains elusive. One of the most frequent genetic alterations identified in TNBC is amplification of the MYC gene which is found in &gt; 60% of samples. The aim of this study was therefore to investigate the potential value of targeting MYC activation with the recently identified selective and high-affinity low molecular weight MYC inhibitor MYCMI-6, for the treatment of TNBC. Methods: Cell viability was determined using the MTT assay and apoptosis by flow cytometry using annexin V-propidium iodide staining. Results: Based on a panel of 13 breast cancer cell lines, IC50 values for inhibition of proliferation by MYCMI-6 ranged from 1.2 to 96.7 μM. Significantly lower IC50 values were found for TNBC than for non-TNBC cell lines (p = 0.04), i.e., TN cell lines were more sensitive to MYCMI-6 than non-TN cell lines. IC50 values for MYCMI-6 were compared with 2 older MYC inhibitors, i.e., 10058-F4 and KJ Pyr 9. Of these 3 inhibitors, the lowest IC50 values were found for MYCMI-6, i.e., MYCMI-6 was the most sensitive of the 3 inhibitors investigated (p &lt; 0.0001 for MYCMI-6 versus both 10058-F4 and KJ Pyr 9). In addition to inhibiting cell proliferation, MYCMI-6 was found to induce apoptosis in a time and concentration-dependent manner in multiple breast cancer cell lines. A significant correlation was found between MYCMI-6 IC50 and induction of apoptosis ((p = 0.0499, r 2 = 0.9026, n = 4), i.e., the lower the IC50 value, the greater the number of apoptotic cells present. This finding suggests that MYCMI-6 decreases cell proliferation by inducing apoptosis. Conclusions: We conclude that the MYC targeting compound, MYCMI-6 is a potential new treatment for TNBC.
HCV in Women and Pregnancy
Authors: Nayantara Orekondy, John Cafardi, Tatyana Kushner, Nancy Reau
Journal: Hepatology (2019)

1Department of HepatologyLoyola University Medical CenterMaywoodIL 2Department of Infectious DiseaseChrist HospitalCincinnatiOH 3Division of Liver Diseases, Icahn School of Medicine at Mount SinaiNew YorkNY 4Section of HepatologyRush University Medical CenterChicagoIL * Address Correspondence and Reprint Requests to: Nayantara Orekondy, M.D. Department of Hepatology, Loyola University Medical Center 2160 S. 1st Avenue Mulcahy Center 1540 Maywood, IL 60153 E‐mail: [email protected]
A community oncology end-of-life care program: Results for hospice length of stay analysis.
Authors: Adil Jamal Akhtar, Jeffrey H. Margolis, Tammy Scott-Barney, Richard Philip Zekman, Andrew A. Muskovitz, Yusuf Qamruzzaman, Samer Ballouz, Mohammed Ibrahim, Karma Maxwell, Lexi Stortz, Maria Fabbiano, Karna Sheth
Journal: Journal of Clinical Oncology (2019)

e23008 Background: Michigan Health Professionals (MHP) is a large multispecialty physician group. MHP Oncology Division participates in quality improvement projects. Palliative and End of Life (EOL) care has been identified as one of the quality improvement areas. A comprehensive community oncology program for early and timely involvement of palliative and EOL care was launched in October 2017. Methods: MHP Palliative and End of life care committee was created of mostly oncologists who are board certified in Palliative care and Hospice. The program, which included pre-program training, user-friendly referral process, and live physician engagement for early involvement of palliative care (PC) and EOL care was developed and implemented. A partnership was created with Premier Hospice to integrate EOL care services with the oncology offices and to collect data. Historical data for average hospice length of stay (LOS) in hospice service for MHP oncology patients was analyzed by Integra Connect. Results: From 1/1/2018 to 12/31/2018 a total of 133 patients (MHP-T) were referred and admitted to Hospice service. Sixty-one patients were on PC service (PC group) and 72 patients (NonPC group) were referred directly to hospice. Total of 527 patients from 2012 to 2017 were analyzed for historical comparison group (HC) and 124 patients were analyzed for MHP-T group. Average LOS was 16.8 days in the HC group. Average LOS for the MHP-T, PC group and NonPC group improved to 34, 35 and 33 days respectively. HC group had 82.2% of patients with average LOS &lt; 30 days. After program implementation average LOS &lt; 30 days improved to 63.7% MHP-T group, 60.0% PC group and 66.7% NonPC group. In HC group, 92 out of 527 patients had average LOS of 2 days or less. Only 2 patients out of 124 patients had average LOS of 2 days or less since the launch of MHP community oncology program. Conclusions: Early and timely patient referral to the EOL care services resulted in average hospice LOS which is more than double as compared to historical comparison group. Fewer number of patients had average LOS of &lt; 30 days and LOS of 2 days or less as compared to the historical comparison group. There was a trend towards higher LOS observed for patients who were under palliative care (PC) before hospice admission.
Adverse events (AEs) with maintenance olaparib in newly diagnosed patients (pts) with advanced ovarian cancer (OC) and a BRCA mutation (BRCAm): Phase III SOLO1 trial.
Authors: Nicoletta Colombo, Kathleen N. Moore, Giovanni Scambia, Ana Oaknin, Michael Friedlander, Alla Sergeevna Lisyanskaya, Anne Floquet, Alexandra Leary, Gabe S. Sonke, Charlie Gourley, Susana N. Banerjee, Amit M. Oza, Antonio González-Martín, Carol Aghajanian, William Hampton Bradley, Jae-Weon Kim, Elizabeth S. Lowe, Ralph Bloomfield, Paul Disilvestro
Journal: Journal of Clinical Oncology (2019)

5539 Background: In SOLO1 (NCT01844986), maintenance olaparib provided a substantial progression-free survival benefit vs placebo in newly diagnosed pts with advanced OC, a BRCAm and clinical complete or partial response to platinum therapy (HR 0.30; 95% CI 0.23–0.41) and was well tolerated (Moore et al. NEJM 2018). We analysed the most common AEs and hematologic AEs in SOLO1. Methods: Pts received olaparib tablets 300 mg twice daily or placebo until progression unless they had no evidence of disease at 2 years, in which case treatment stopped. AEs were graded using CTCAE v4.0. Results: Of 391 pts randomized, 390 (olaparib, 260; placebo, 130) were treated and included in the safety analysis. Median treatment duration was approximately 25 months for olaparib vs 14 for placebo. Median time to first onset of the most common AEs (nausea, vomiting, fatigue/asthenia, anemia) and neutropenia and thrombocytopenia was &lt; 3 months; the first event lasted a median of &lt; 2 months, apart from fatigue/asthenia, which lasted a median of &lt; 4 months (Table). AEs were usually managed with supportive therapy and/or dose modification; few pts discontinued. Conclusions: AEs in newly diagnosed pts with advanced OC treated with olaparib usually occurred early and were manageable, with few discontinuations. Clinical trial information: NCT01844986. [Table: see text]
Estimating the Attributable Cost of Physician Burnout in the United States
Authors: Shasha Han, Tait D. Shanafelt, Christine A. Sinsky, Karim M. Awad, Liselotte N. Dyrbye, Lynne C. Fiscus, Mickey Trockel, Joel Goh
Journal: Annals of Internal Medicine (2019)

Although physician burnout is associated with negative clinical and organizational outcomes, its economic costs are poorly understood. As a result, leaders in health care cannot properly assess the financial benefits of initiatives to remediate physician burnout.To estimate burnout-associated costs related to physician turnover and physicians reducing their clinical hours at national (U.S.) and organizational levels.Cost-consequence analysis using a mathematical model.United States.Simulated population of U.S. physicians.Model inputs were estimated by using the results of contemporary published research findings and industry reports.On a national scale, the conservative base-case model estimates that approximately $4.6 billion in costs related to physician turnover and reduced clinical hours is attributable to burnout each year in the United States. This estimate ranged from $2.6 billion to $6.3 billion in multivariate probabilistic sensitivity analyses. At an organizational level, the annual economic cost associated with burnout related to turnover and reduced clinical hours is approximately $7600 per employed physician each year.Possibility of nonresponse bias and incomplete control of confounders in source data. Some parameters were unavailable from data and had to be extrapolated.Together with previous evidence that burnout can effectively be reduced with moderate levels of investment, these findings suggest substantial economic value for policy and organizational expenditures for burnout reduction programs for physicians.
Patients preference in receiving phone call from oncologist after cancer diagnosis and before in person consultation.
Authors: Amit Arora, Tatjana Kolevska, Jose Jiminez
Journal: Journal of Clinical Oncology (2019)

e18044 Background: Diagnosis of cancer creates an emotionally challenging time for patients. Waiting period between receiving diagnosis, and formal consultation with an Oncologist is associated with fear, shock, and uncertainty. Understanding patients’ preferences during this sensitive period is essential in providing high quality care. We hypothesized that receiving a call from an Oncologist, while waiting for a formal consultation, would help patients cope with cancer diagnosis. Methods: To assess our hypothesis, we surveyed 171 patients across five Kaiser Permanente medical centers. All patients received a call from an Oncology navigator to onboard them, and assure completion of necessary tests before in-person consultation with Oncologist. Of the 171 patients surveyed, 61 patients received an additional call from their assigned Oncologist before a formal in-person consultation. To understand the impact of the call made by the Oncologist, a survey was administered to patients within a few weeks of consultation. The remaining 110 patients who only received a call from an Oncology navigator were also surveyed to determine if a call from an Oncologist before their consultation could have helped them cope better with their cancer diagnosis. Results: Approximately 45 % of surveyed patients (n = 171) preferred a call from an Oncologist before the formal consultation. Conclusions: Brief telephone contact by Oncologist before in-person consultation supports newly diagnosed cancer patients with high-levels of uncertainty and shock. A substantial portion of newly diagnosed cancer patients prefers to speak with an Oncologists in the days after receiving a cancer diagnosis, and those who do receive an Oncologist call, find it beneficial in coping with their diagnosis.[Table: see text]
Body Mass Index (BMI), BMI Change, and Overall Survival in Patients With SCLC and NSCLC: A Pooled Analysis of the International Lung Cancer Consortium
Authors: Daniel Shepshelovich, Wei Xu, Lin Lu, Aline Fares, Ping Yang, David Christiani, Jie Zhang, Kouya Shiraishi, Brid M. Ryan, Chu Chen, Ann G. Schwartz, Adonina Tardon, Xifeng Wu, Matthew B. Schabath, M. Dawn Teare, Loic Le Marchand, Zuo-Feng Zhang, John K. Field, Hermann Brenner, Nancy Diao, Juntao Xie, Takashi Kohno, Curtis C. Harris, Angela S. Wenzlaff, Guillermo Fernandez-Tardon, Yuanqing Ye, Fiona Taylor, Lynne R. Wilkens, Michael Davies, Yi Liu, Matt J. Barnett, Gary E. Goodman, Hal Morgenstern, Bernd Holleczek, M. Catherine Brown, Geoffrey Liu, Rayjean J. Hung
Journal: Journal of Thoracic Oncology (2019)
Predictive score for recurrence after complete resection in locally advanced oral cavity squamous cell carcinoma.
Authors: Hsueh-Ju Lu, Szu-Wen Tseng, Chih-Yu Peng, Hsien-Chun Tseng, Chung-Han Hsin, Wei-Shiou Huang, Ming-Fang Wu, Muh-Hwa Yang, Mu-Hsin Chang
Journal: Journal of Clinical Oncology (2019)

e17536 Background: Early progression, usually defined disease-free interval (DFI) less than six months after completing adjuvant platinum-based chemoradiotherapy (CRT), has very poor outcome for oral cavity squamous cell carcinoma (OCSCC). But there are no biomarkers to predict such early progression. Methods: Locally advanced OCSCC patients, after complete surgical resection and followed-up platinum-based adjuvant CRT, were retrospectively enrolled from Chung Shan Medical University Hospital (CSMUH, training cohort) and Taipei Veterans General Hospital (TPE-VGH, validating cohort) in Taiwan. Clinicopathologic variables of patients with DFI &lt; or ≥ 6 months were compared by using the χ 2 test. The Cox proportional hazards model was applied to identify independent factors for DFI. Survival was estimated using the Kaplan-Meier method and log-rank test. Results: A total of 350 high-risk OCSCC patients were enrolled, including 146 patients in training cohort and 204 in validating cohort. In multivariate Cox regression, pN &gt; 0, extracapular spread, and depth of invasion ( ≥ 1cm) were independent factors for DFI in training cohort. If each factor scored one point, the scoring system could effectively predict early progression that sensitivity/specificity/area under curve (AUC) of training and validating cohort were 57.7%/91.2%/0.771 and 58.1%/83.9%/0.730, respectively (the cutoff level ≤ 2 or &gt; 2). DFI between lower- (score 0–2) and high- (score 3) risk groups were also significantly different in both training (median DFI, 59.6 vs. 4.5 months, P &lt; 0.001) and validating cohorts (NA vs. 9.3 months, P &lt; 0.001). Conclusions: The established score system was effective to predict early progression after adjuvant CRT for locally advanced OCSCC.
Gemcitabine and nab-paclitaxel retreatment as a third-line therapy following second-line FOLFIRINOX for advanced pancreatic adenocarcinoma.
Authors: Andrew Peter Dean, Adarsh Das, Meabh McNulty, Domenic Higgs
Journal: Journal of Clinical Oncology (2019)

e15794 Background: First-line and second line treatment for advanced pancreatic adenocarcinoma typically involves therapy with gemcitabine plus nab-paclitaxel, FOLFIRINOX or as per the recent phase III trial (NAPOLI-1), the combination of nal-irinotecan with 5-fluorouracil and leucovorin. Despite these advances, there remains minimal amount of data regarding the options for, or efficacy of, third-line treatment in these patients. We have previously reported our experience of twenty patients who received effective third-line therapy with gemcitabine plus nab-paclitaxel retreatment after receiving FOLFIRINOX as second-line treatment. This retrospective analysis assessed the updated data of the use of gemcitabine plus nab-paclitaxel as a third-line treatment option in a single hospital setting. Methods: We conducted a retrospective analysis using an electronic database of patients with locally advanced or metastatic pancreatic adenocarcinoma who received first-line gemcitabine and nab-paclitaxel, second line FOLFIRINOX and third-line retreatment with gemcitabine and nab-paclitaxel between January 2013 and December 2018. All patients had an ECOG performance status of 2 or less. Overall survival (OS) was estimated by the Kaplan-Meier method. Results: Twenty-six patients were reviewed. Median age of 73 (range, 45 – 81). 73% of the studied patients had locally advanced cancer at diagnosis. The median OS from diagnosis was 39.0 months (95% CI, 34.0 – 66.0). The median OS from third-line re-initiation of gemcitabine plus nab-paclitaxel was 18.0 months (95% CI, 9.0 – 32.0). Conclusions: This is one of the first retrospective studies to show the efficacy of third-line treatment with gemcitabine plus nab-paclitaxel in advanced pancreatic cancer. It demonstrated that retreatment with gemcitabine plus nab-paclitaxel is feasible, tolerable and effective in patients with a good performance status. We suggest a formal phase 3 study to confirm our data and potentially establish a formal new standard of care for third line chemotherapy in this previously disadvantaged group.
How to deal with second line dilemma in metastatic colorectal cancer? A systematic review and meta-analysis.
Authors: Antonio Galvano, Aurelia Guarini, Stefania Cusenza, Nadia Barraco, Marta Castiglia, Lorena Incorvaia, Sergio Rizzo, Fabio Fulfaro, Giordano D. Beretta, Ignazio Ugo Carreca, Viviana Bazan, Antonio Russo
Journal: Journal of Clinical Oncology (2019)

e15006 Background: Monoclonal antibodies targeting epidermal growth factor receptor (EGFR) or vascular endothelial growth factor (VEGF) have demonstrated efficacy in combination with chemotherapy as second line for metastatic colorectal cancer (mCRC). However, there is still a paucity of evidence or guidelines suggesting the right sequential treatment in all RAS (KRAS/NRAS) wild type(wt)mCRC. Therefore, we aimed to evaluate the impact of these targeted therapies by reviewing literature data. Methods: We used Cochrane, EMBASE and Medline databases to select phase III clinical trials containing efficacy and safety data about chemotherapy (CT) or CT + targeted agents combination (Anti-VEGF and Anti-EGFR) in second line mCRC setting. We performed direct comparisons to obtain pooled data for anti-VEGF + CT versus CT and anti-EGFR +CT versus CT comparisons. Then we performed indirect comparisons between anti-EGFR and Anti-VEGF. Outcomes were disease control rate (DCR), response rate (RR), progression-free survival (PFS), overall survival (OS) and most common G3-G5 toxicities. Results: Eight eligible RCTs (6793 pts) were included: 5 studies compared anti-VEGF + CT and 3 anti-EGFR + CT combinations to CT. After direct comparisons, pooled indirect results showed significantly improved OS (HR 0.83, 95% CI 0.72–0.94) and DCR (HR 1.27, 95% CI 1.04–1.54) favouring anti-VEGF combinations in overall population; however, no statistically significant differences in all RAS wt patients was observed (HR 0.87, 95% CI 0.70–1.09). Additionally, anti-EGFR combinations significantly increased ORR in all patients (RR 0.54, 95% CI 0.31–0.96), showing a trend in all RAS wt patients (RR 0.63, 95% CI 0.48–0.83) too. Furthermore, no significant difference in PFS and DCR all RAS was registered. Anti-VEGF combination significantly increased Only a significant asthenia difference (RR 1.34, 95% CI 1.03–1.75) was registered. Conclusions: At our knowledge, our indirect comparisons between anti-VEGF and anti-EGFR combinations showed for the first time better OS and DCR for anti-VEGF combinations, whereas better RR is observed for anti-EGFR combinatory regimens, defining a role of both targeted agents in second line mCRC setting.
Effect of neoadjuvant chemotherapy using gemcitabine and S1 before surgery for pancreatic cancer on quality of life.
Authors: Naoko Sato, Fuyuhiko Motoi, Masahiro Iseki, Kei Kawaguchi, Fumiko Sato, Yu Katayose, Michiaki Unno
Journal: Journal of Clinical Oncology (2019)

e15719 Background: To improve the poor prognosis of patients with pancreatic cancer, we examined the effect of 6 months of neoadjuvant chemotherapy (NAC) using gemcitabine and S1 before surgery and found significantly prolonged survival. Clinical use of this treatment is expected in the future. However, preoperative NAC may increase the physical burden on patients as well as their psychological burden due to the longer waiting time. Thus, it is necessary to confirm that the treatment does not reduce quality of life (QOL). Methods: In this observational study of patients who underwent resection after this NAC, a QOL questionnaire survey was administered preoperatively and at postoperative months 3, 6, and 12, to consenting patients from those enrolled in randomized controlled trials (RCTs). The intervention group (planned surgery and NAC) had added pre- and post-treatment QOL surveys. We used the Short Form 36 Health Survey version 2 (SF-36v2 Standard, Japanese) to measure health-related QOL. Overall differences among the groups were evaluated by paired t test and two- and three-way ANOVA. All statistical analyses were performed using SPSS (ver. 21) software. Results: In total, 55 patients (mean age 66.0 years), about 15% of those enrolled in the RCTs, responded to the questionnaire (NAC group, n = 22; control group, n = 33). QOL was not significantly reduced in the NAC group pre- and post-treatment ( p= 0.19-0.96). Notably, there were no significant differences in post-treatment QOL, with improvement in the Physical Functioning (75.9→79.4), Bodily Pain (70.5→72.5), Vitality (59.6→59.9), and Mental Health (66.5→69.7) SF-36 domains compared with before preoperative treatment. This suggests that patients had good preoperative physical and mental QOL. QOL at each time point did not differ significantly in the 8 domains with or without NAC; the Mental component summary score was significantly higher in the NAC group compared with the control group at 3 months (54.9 vs 49.3, p= 0.04). NAC and QOL did not differ significantly by time, sex, and operation type. Conclusions: NAC using gemcitabine and S1 before surgery for pancreatic cancer does not reduce QOL. Improved prognosis can be expected with no adverse effect on QOL.
Risk of cancer in first-degree relatives of childhood cancer patients: A linked longitudinal population-based registry study.
Authors: Laura-Maria Madanat-Harjuoja, Janne Pitkäniemi, Elli Hirvonen, Nea Malila, Lisa Diller
Journal: Journal of Clinical Oncology (2019)

1522 Background: Population based data on risk of cancer in relatives of childhood cancer patients are sparse. Using linked population-based registries, we set out to evaluate risk of early onset cancer in first-degree relatives of childhood cancer patients. Methods: We queried the Finnish Cancer Registry and ascertained a cohort of 9135 individuals diagnosed with at least one cancer under the age of 21 years between 1970 and 2012. We then went on to identify a total of 58,211 unique first- and second-degree relatives by linking to the Central Population Registry. Relatives were then linked back to the annually updated Finnish Cancer Registry to identify cancer diagnoses in siblings, offspring and parents of childhood cancer patients, restricting to cancers occurring under the age of 40. Risk of cancer in relatives of the index case was estimated using standardized incidence ratios (SIRs) comparing cancer age and period specific incidence in relatives to that of the general population. Results: A total of 288 cancers were diagnosed in relatives during the 900,907 years of follow-up, while 266 cancers were expected. The overall risk of cancer in siblings of childhood cancer patients was elevated (SIR 1.18 95% CI 1.00-1.39). 144 of the childhood cancer patients were identified as having a sibling additional to index case with a diagnosis of cancer at age &lt; 40; 44 of these 144 also had a parent with early onset cancer. The risk of early onset cancer was elevated in offspring overall (SIR 1.79 95%CI 1.05-2.81) and in offspring of retinoblastoma, malignant bone tumor and neuroblastoma patients. Siblings of lymphoma patients were at elevated risk of early cancer, and the mothers of 11 of 27 sibling pairs (lymphoma + cancer &lt; 40 yo) also had cancer at age &lt; 40. Conclusions: Linked registries allow family history of cancer to be evaluated across multiple relatives and to be longitudinally updated. Results are generally reassuring with regard to risk of cancer in relatives of childhood cancer patients. Elevated risk in relatives of retinoblastoma and malignant bone tumor patients are in line with the known cancer syndromes associated with these tumor types, and lymphoma and neuroblastoma families need further analysis.