tbuckley/cabot-search huggingface dataset:
The role of real-world evidence in clinical care: A survey of oncology leaders.
Authors: Melissa Stahl, Alissa M Winzeler, Ali Zaman, Nicole Shelby, James Lin Chen, Bryan Clutz, Aradhana Ghosh, Jonathan Hirsch
Journal: Journal of Clinical Oncology (2018)

e18515 Background: Many health systems seek the ability to share and learn from real-world evidence, or aggregated cancer patient data, to improve patient outcomes. Although precision medicine initiatives are becoming more commonplace at large health systems, there is limited data defining the attitudes of health system leaders on their views of precision medicine. To this end, the Health Management Academy conducted a survey of oncology leaders to explore their views on the application of real-world evidence in clinical oncology. Methods: In August 2017, the Health Management Academy surveyed leaders from 43 leading health systems regarding their awareness, integration, and operationalization of precision medicine. The survey included 48 questions that assessed the state of precision medicine, challenges with clinical decision making, and reimbursement policies. Four questions addressed data sharing and impact of real-world evidence on clinical decision making. Health system leaders were contacted via email. Results: We obtained a response rate of 49% (21/43). Respondents included Chief Medical Officers (CMOs) and oncology leaders representing 21 health systems, 296 hospitals, and approximately 2.9 million admissions annually. 80% of respondents expect real-world outcomes from aggregated, de-identified data to be “extremely important” in guiding physician decision making in complex cases. 63% of respondents considered providing oncologists with clinical guidance for molecular diagnostics and targeted therapies “extremely important”. 60% of responding health systems are involved in a cancer data sharing collaboration, most commonly the Oncology Precision Network (44%). Most (73%) respondents would find a tool that compared real-world outcomes across treatment regimens for patients with any combination of clinical and molecular characteristics “extremely valuable”. Conclusions: Real-world evidence to improve patient care remains a critical priority among health system leaders. Furthermore, these leaders recognize that decision support tools will be required to make this data actionable for clinicians at their individual points of care.
Apatinib plus S-1 as second-line or laterline chemotherapy for advanced squamous cell lung carcinoma.
Authors: Qingming Shi, Liming Xia, Jinhua Zhou, Zi'an Wang, Guangming Wang, Xianping Cheng, Xinzhong Li, Fangqing Wang, Fengde Zhao, Xuechao Li, Yiping Zhu, Jun Xie, Bin Ye
Journal: Journal of Clinical Oncology (2018)

e21179 Background: Apatinib, an oral VEGFR2 inhibitor, has been proved a confirming activity for inhibiting tumor growth on lung cancer in vitro and in vivo tests.This prospective study tried to investigate the efficacy and safety of apatinib plus S-1 as second- or third-line treatment in patients with advanced squamous cell lung carcinoma. Methods: In this open-label single-arm study, eligible patients (pts) had histologically or cytologically confirmed advanced squamous cell lung cancer and had documented disease progression after at least one platinum-based chemotherapy. Patients were treated oral apatinib (250-500 mg daily) and S-1(60mg/m2 D1-14) (allowable dose adjustment) , repeated every 3 weeks. Treatment will be continued until disease progression or unacceptable toxicity occurs. Results: From August 19, 2016 to January 29, 2018, 27 pts were enrolled. there were 19 pts available for efficiency evaluation. Among them, 7 achieved partial response (PR),10 had stable disease (SD), and 2 had progressive disease(PD), resulting in an overall response rate of 36.8% and a disease control rate of 89.5%. The mPFS is 5.0m(95%CI:3.4-6.54), The real mPFS will be longer as this study continues. The common adverse events (AEs) were hypertension (n = 5, 18.5%), fatigue (n = 4, 14.8%), hand-foot skin syndrome (n = 6, 22.2%) and pulmonary infection (n = 4, 14.8%).In addition, serious adverse events (SAEs) were hypertension (n = 2, 7.4%),diarrhea (n = 1, 3.7%), proteinuria (n = 1, 3.7%), thrombocytopenia (n = 2, 7.4%),hand-foot skin syndrome (n = 1, 3.7%), pulmonary infection (n = 3, 11.1%). Others like hoarse voice, oral ulcers, constipation, anemia, elevated bilirubin, leukopenia appeared in 1 of 27 patients respectively and could be better controlled. Overall incidence of AEs and SAEs was 74.1%, 37.0% respectively. No treatment-related death occurred. Conclusions: Apatinib plus S-1 showed promising efficacy and acceptable toxicity in advanced squamous cell lung carcinoma. The research is still ongoing. The results are subject to the verification of phase Ⅲ randomized clinical trials. Clinical trial information: ChiCTR-OPC-16009048 Clinical trial information: ChiCTR-OPC-16009048.
Evaluation of IL-2 in sustaining the PD-L1 blockade‒mediated reinvigoration of T cell function in melanoma.
Authors: Hui Yan, Hedong Zhang, Tao Jiang, Wenhao Chen
Journal: Journal of Clinical Oncology (2018)

e24145 Background: T cell exhaustion represents a distinct T cell differentiation state following antigen encounter. Exhausted T cells that arise during cancer progression sustainably express PD-1; blockade of PD-1/PD-L1 immune checkpoint thus has had startling success in human melanoma. Nevertheless, durable clinical benefit of PD-1/PD-L1 blockade is still not achieved in most patients. Recent reports indicated that reinvigoration of exhausted T cells in mice by PD-L1 blockade was transient, and reinvigorated T cells became re-exhausted if antigen concentration remained high. Here we investigated whether IL-2 treatment sustains the PD-L1 blockade‒mediated reinvigoration of T cell function in melanoma. Methods: B16-F10 inoculated B6 mice were adoptively transferred with 2 million activated Pmel-1 cells (48 hours after in vitro stimulation with gp10025–33) on day 3, and injected i.p. with 400 μg anti-PD-L1 (clone 10F.9G2) on days 3, 6, 9 and with 5 μg human IL-2 b.i.d. until a tumor size of 1000 mm3was reached. Tumor progression was determined and tumor infiltrating T cells were analyzed by flow cytometry. Results: In B16-F10 inoculated mice with or without Pmel-1 cell transfer, anti-PD-L1 plus IL-2 more potently inhibited tumor progression than did anti-PD-L1 or IL-2 alone. In B16-F10 inoculated mice transferred with Pmel-1 cells, majority of infiltrating Pmel-1 cells in B16 melanoma lost IFN-γ production within 20 days post initial PD-L1 blockade alone (only 8-25% infiltrating Pmel-1 cell expressed IFN-γ). By contrast, at 20 days post initial PD-L1 blockade plus IL-2 treatment, 40-50% Pmel-1 cells infiltrating in melanoma produced IFN-γ, an indication of T cell function. Conclusions: IL-2 treatment sustains the PD-L1 blockade‒mediated reinvigoration of T cell function in melanoma. These findings may have important clinical implications for patients with melanoma.
A retrospective study of 83 pancreatic cancer patients treated by combining chemotherapy with NK cell-enriched immunotherapy.
Authors: Kenta Narumi, Sanehiko Fujita, Junichi Masuyama
Journal: Journal of Clinical Oncology (2018)

e15063 Background: Natural killer (NK) cell-enriched immunotherapy (NK-IT) is a favorable candidate for cancer treatment because NK cells possess potent killing activity against malignant cells. Recently, we reported a novel method for NK cell expansion through co-stimulation of peripheral blood (PB) mononuclear cells with anti-CD3 and anti-CD52 (alemtuzumab) antibodies (Cytotherapy 2016). Using expanded NK cells by this method, we have conducted NK-IT in combination with standard treatments for 83 patients with pancreatic cancer (PC) since 2006. We retrospectively analyzed the clinical outcomes and immunological changes in PB lymphocytes after NK-IT. Methods: All patients were diagnosed with locally advanced or metastatic PC, which was confirmed by histology, cytology, or typical CT/MRI imaging. NK-IT was repeatedly administered at 2-week intervals with a cell product generated from 30 ml of PB per session. Overall survival (OS) was defined as the time from the start date of first-line treatment to death. Immunological monitoring of PB was carried out just before and 2-3 months after NK-IT. Results: There were 50 patients with ECOG PS 0-1 and 33 patients with PS 2-3 who mostly received chemotherapy with gemcitabine or S-1. The median OS and survival time (ST) after NK-IT were 14.9 months and 11.5 months for PS 0-1, respectively, and 7.2 months and 3.9 months for PS 2-3, respectively. The 1-year survival rate was 60% for PS 0-1 and 18% for PS 2-3. The median cell number and NK cell proportion in the cell products were 13.3 x 109and 39.8% for PS 0-1, and 12.5 x 109 and 27.5% for PS 2-3. Immunological monitoring of PS 0-1 revealed that NK-IT induced a significant increase in NK cytotoxic activity and lymphocyte count, and a significant decrease in neutrophil/lymphocyte and CD4/CD8 T cell ratio in the long-term survivors (ST ≥ 11.5 months) but not in the short-term survivors (ST < 11.5 months). The rise in the numbers of NK cells and NKG2D+ cells was significantly higher in the long-term survivors than in the short-term survivors. Conclusions: Our findings suggest that sustained enhancement of cytotoxic profiles in PB lymphocytes after NK-IT may extend survival with combination therapy in patients with PS 0-1.
Oral oncolytic adherence and confidence in self-managing side effects among a sample of Michigan oncology practices.
Authors: Emily Mackler, Teresa M Salgado, Jane Severson, Jamie Lindsay, Peter Batra, Laura Petersen, Karen B Farris
Journal: Journal of Clinical Oncology (2016)

6594 Background: The aim was to assess medication adherence and confidence to self-manage side effects of oral oncolytic agents among cancer patients whose providers participate in the Michigan Oncology Quality Consortium. Methods: This was a cross-sectional study conducted in 2015, enrolling a convenience sample of 125 patients currently taking oral oncolytics in 10 practices. Respondents completed an online survey containing demographics, clinical information, adherence (thinking about the past 4 weeks, rate your ability to take your {medication} as prescribed), reasons for non-adherence, health literacy (3 items) and Patient Activation Measure (PAM, 13 items). Participants were also asked to rate how confident they felt self-managing 3 common oral oncolytic side-effects. Differences in adherence and confidence by age, gender, education level, health literacy, and PAM level were examined. Results: Respondents were 66.2 (SD 13.6) years old and 58% were female. Adherence to oral oncolytics was excellent for 71% patients, very good for 18% and good or fair for 11%. Experiencing side effects was the most common reason for non-adherence (8.0%). 74% of patients had high levels of patient activation. Confidence to manage fatigue was high for 79% of patients, moderate for 12% and low for 9%. Confidence to manage nausea and diarrhea was higher with 86% and 89% patients reporting high confidence, respectively, but 6% and 5% reported low confidence. When combining the confidence measures to manage the 3 symptoms, patients with higher health literacy (p = 0.001), higher PAM levels (p = 0.018) and older patients (p = 0.04) exhibited statistically higher confidence. No significant differences were found relative to these factors for patients with excellent medication adherence compared to less than excellent. Conclusions: About 30% of respondents reported non-adherence and 12-20% expressed moderate or low confidence to manage side effects. Strategies to improve adherence by focusing on management of side effects is a logical next step. Health literacy screening in clinical practice may be an efficient means to identify patients with low self-management confidence who need additional education and support.
Venetoclax (VEN) in patients with relapsed/refractory non-Hodgkin lymphoma (NHL).
Authors: Matthew Steven Davids, Andrew Warwick Roberts, John Francis Seymour, William G. Wierda, Soham D. Puvvada, Lori A. Gressick, Debbie Alter, Lang Zhou, Su Young Kim, Maria Verdugo, John F. Gerecitano
Journal: Journal of Clinical Oncology (2017)

e19041 Background: VEN is a selective orally bioavailable BCL-2 inhibitor. The dose-escalation Phase 1 study of VEN in 106 patients (pts) with relapsed/refractory NHL reported an ORR of 44%. Most pts had diffuse large B-cell/follicular lymphoma; we report on updated results in pts with less common NHL subtypes. Methods: VEN was administered and continued until progressive disease (PD)/unacceptable toxicity, in dose cohorts ranging from 300–1200 mg. Adverse events (AEs) were assessed by NCI-CTCAE v4.0 and response by 2007 Cheson IWG response criteria, utilizing CT scans beginning at wk 6. Results: 35 of 106 pts had mantle cell lymphoma (MCL, n=28), marginal zone lymphoma (MZL, n=3) or Waldenström macroglobulinemia (WM, n=4). Most common all grade treatment emergent AEs were nausea (51%), diarrhea (49%) and fatigue (34%); grade 3/4 AEs in &gt;10% of pts were neutropenia and anemia (17% each). Laboratory TLS was reported in a single pt (bulky MCL). MCL pts (median age: 72 years) had received a median of 3 (1–7) prior treatments (tx). Median time from start of prior tx to start of VEN was 13 mo (2–148) and time on VEN was 11 mo (0.2–42). ORR was 75%, 6 pts (21%) achieved CR and remain on study (DORs: 25–40 mo). One pt with a PR proceeded to elective allogeneic stem cell transplant and remained disease free at last protocol defined follow-up (24 mo after coming off study). Median PFS was 11 mo and DOR was 15 mo. MZL pts (median age: 63 years) had received a median of 4 (2–6) prior tx. Time from start of prior tx to start of VEN was 8, 14, 73 mo and time on VEN was 5, 1, 35 mo. One pt (6 prior tx) received VEN for &lt;1 mo due to progressive cytopenias; 1 pt (4 prior tx) achieved a PR with VEN at wk 6 but had PD at wk 16; 1 pt (2 prior tx) achieved PR at wk 6 and is the only pt to remain on study (DOR:32 mo). WM pts (median age: 67 years) had a median of 4 (3–5) prior tx. Time from start of prior tx to start of VEN was 5, 18, 33, 67 mo and time on VEN was 42, 17, 54, 20 mo. All pts achieved PR (at wks 6 [n=2], 16 and 36), with DORs of 11, 12, 38 and 50+ mo (latter is ongoing and remains on study). Conclusions: VEN monotherapy has a tolerable safety profile in MCL, MZL and WM pts. ORR were high and most responses durable; median PFS and DOR suggest significant activity in MCL pts. Further investigation of VEN in each disease is indicated. Clinical trial information: NCT01328626.
Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired commercial next-generation sequencing assays.
Authors: Catherine Callaghan Coombs, Nancy Gillis, Kelly L Bolton, Jonathan S. Berg, Xianming Tan, Michele C Hayward, Nirali M. Patel, Markus Ball, Maria Balasis, Tania MESA, Nathan Montgomery, Kristy L. Richards, William Y. Kim, David N. Hayes, Shelton Earp, Joel S. Parker, Ross L. Levine, Elli Papaemmanuil, Ahmet Zehir, Eric Padron
Journal: Journal of Clinical Oncology (2018)

12068 Background: Precision medicine is increasingly utilized for both prognostication and application of targeted therapies for oncologic patients (pts). Results from next-generation sequencing (NGS) assays ideally should reflect the burden of somatic tumor mutations (muts), yet challenges can arise from differentiation of germline muts and from contamination of biopsies by non-tumor tissue. Clonal hematopoiesis (CH), defined by the presence of somatic muts typically in leukemia-associated genes in hematopoietic cells, occurs in aging individuals, with an increased risk for hematologic cancers and shorter survival in pts with solid tumors (ST). Here we examine the prevalence of CH leading to false positive (FP) calls on commercial NGS assays. Methods: This is a multi-institution, retrospective cohort study of pts undergoing NGS of ST. All pts undergoing commercial NGS (Foundation Medicine) testing were examined (N = 768 at UNC and 989 at MCC). For a subset of pts (N = 64 at UNC and 30 at MCC), NGS of paired blood samples was performed to examine the prevalence of true CH events, defined as a variant allele frequency (VAF) in the blood exceeding the VAF in the tumor tissue. Germline events were defined by VAF > 35% in both tumor and blood. Results: Muts in genes that are frequently altered in CH (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) were identified in 65% of pts; excluding TP53, often mutated in ST, these events were seen in 35% of pts. A bimodal distribution of VAFs was seen for CH genes, with low VAF events most suggestive of true CH events. Using paired blood samples, we confirmed such muts as true CH events in 9.4% of ST pts in the UNC cohort. Across all genes, germline events were reported in 23% of UNC pts, of which 33% were known or likely pathogenic variants. MCC samples were enriched for pts with reported muts in CH genes; 33% of which (10/30) were confirmed as true CH events. The majority of DNMT3A muts (64%, 7/11) were CH; the minority of TP53 muts (4%, 2/50) were CH. Conclusions: Muts in CH genes are commonly reported on unpaired clinical NGS testing of ST; some are true CH events as opposed to TS events. It is important to recognize CH as a possible FP when applying NGS results to pt care.
Association of hypermethylation at the <i>NDRG4</i> CpG island with the risk of gastric cancer.
Authors: Jieer Ying, Cong Luo, Cong Li, Qi Xu
Journal: Journal of Clinical Oncology (2016)

e15530 Background: N-Myc downstream regulated gene 4 (NDRG4) is a candidate tumor suppressor gene whose hypermethylation was reported to contribute to the risk and poor prognosis of colorectal cancer, meningioma, and glioblastoma. Here we tested whether NDRG4 methylationwas associated with the risk and the prognosis of gastric cancer. Methods: A fragment (hg19: chr16:58535416-58535478) on the CpG islandof NDRG4 wasselected in the current methylation assay, which measured a total of five CpG sites among 110 pairs of gastric cancerand its adjacent tissues using the bisulfite pyrosequencing technology. Pearson χ2 test, Fisher’s exact test or Cox proportional hazard models were applied to assess the association of NDRG4 methylation with clinicopathological phenotypes and survival outcomes. Results: Our data showed that NDRG4 average methylation level was significantly increasedin tumors compared with their matched adjacent tissues (19.87 ± 11.88% versus 13.80 ± 4.38%, P < 0.001). There were 40 (36.36%) of 110 tumors with over 19.87% average methylation of NDRG4, which was significantly associated with age (P < 0.001) and tumor differentiation (P = 0.004). Meanwhile, multivariate linear regression showed that there was an age-dependent mode of changed methylation level (r = -0.349, adjusted P = 0.001). Further data mining in the Cancer Genome Atlas (TCGA) dataset showed a significantly reverse correlation between NDRG4 methylation and gene expression (P < 0.001), suggesting a pivotal role of NDRG4 methylation in the regulation of gene function. Conclusions: In conclusion, NDRG4 hypermethylation was significantly associated with the risk of gastric cancer.Age-dependent mode of changed methylation level might be a relevant marker for gastric cancer prognosis.
Anxiety, depression in lung cancer and the predictive role of unmet needs: Data from a national multicenter study (E-LUNG).
Authors: Mario Airoldi, Marco Miniotti, Valentina Ieraci, Marcello Tiseo, Enrico Cortesi, Gianpiero Fasola, Milena Vitali, Carmelo Iacono, Alessandro Morabito, Rossana Berardi, Riccardo Torta
Journal: Journal of Clinical Oncology (2016)

10062 Background: Patients centricity is relevant to garantee the best quality of life during diagnostic and therapeutic approaches. Therefore is essential to consider, besides the patient perception, the evaluation of unmet needs from caregivers, nurses and oncologists. The aim of this multicenter study was to determine these perceptions and to explore the predictive power of unmet needs on anxiety and depression. Methods: Using the Supportive Care Needs Survey (SCNS-SF34),1616 interviewes from lung cancer patients, caregivers, oncologists and nurses were collected to evaluate the perceived supportive care needs inherent to have lung cancer (LCN). Patients were also asked to complete the Hospital Anxiety and Depression Scale (HADS) and the Distress Thermometer (DT). To study the predictive power of LCN on anxiety and depression, a hierarchical binomial logistic regression (HBLR) was performed. Results: Overall, patients perceived that their supportive care needs have been met on average; item level analyses showed that specific needs of the Psychological and the Physical & Daily living domains were perceived as unmet, even with relevant frequencies when the intensity of the need was considered to be moderate or high. With regard to the between-groups differences, emerged that caregivers, oncologists and nurses significantly outscored patients in all the domains considered (with the exception of the Sexuality needs domain for caregivers). Having used the cut-off values for cancer populations, the 62.4% of e-Lung patients showed psychological distress, while the 45.0% reported anxiety and depression. HBLR showed satisfactory measures of model fit (Negelkerke R square2 = 0.458.) and identifyed the Psychological needs (OR = 1.133, χ2Wald(1) = 28.735, p< 0.001) and Health System (OR = 1.088, χ2Wald(1) = 6.395, p= 0.011) and Information needs domains as significant predictors. Conclusions: Findings from e-LUNG study confirm a significant link between LNC and anxiety and depression and suggest that these issues should be taken into account to provide a best Quality of Life for cancer patients.
Watch and wait management of rectal cancer after neo adjuvant treatment, short-term outcome and morbidity of salvage surgery: A single center experience.
Authors: Mohammed Alharthi, Olivier Charette, Carole Richard, Eric Debroux, Francois Dagbert, Richard Ratelle, Ramses Wassef, Rasmy Loungnarath
Journal: Journal of Clinical Oncology (2018)

e15692 Background: Watch and wait protocol in patients with complete clinical response after neo-adjuvant therapy for rectal cancer has shown encouraging results with adequate follow up, allowing patients to avoid morbidities related to surgery. Methods: Retrospective study Between April 2008 and May 2017 was conducted in our center. 36 patients with rectal cancer of stage I to III according to UICC, treated with neo-adjuvant radiochemotherapy RCT, radio brachytherapy R-BT, brachytherapy BT, and brachy-chemotherapy BCT that had CCR were included. CCR was identified through digital rectal examination, endoscopy and MRI. Follow up was set according to guidelines reported in literature. Each patient had digital rectal examination, flexible recto-sigmoidoscopy with/without biopsy, and MRI every 3 months for the first 2 years. Results: 36 patients were included. Initial stage was assessed with MRI in 32 patients and ERUS in 23 patients. 8.3% were stage I, 63.9% stage II, 27.8% stage III. The mean distance from anal margin was 5cm. The neo-adjuvant protocol was RCT in 77.8%, R-BT in 5.6%, BT in 13.9%, and BCT in 2.7%. Patients were assessed for tumor response at an average of 8.2 weeks from the end of the treatment. 6 patients were operated for local recurrences 16.6%. All local recurrences were diagnosed within the first year. The overall morbidity in the operated patients was acceptable. The complications were class I Clavien-Dindo 57% in 4 patients, 1 patient had class II complication 14%, 1 patient had class III complication 14%, and 1 patient had class IV complication 14%. 50% of the patients had positive surgical resection margin. 1 patient had complete pathological response on the histopathology. Conclusions: Concomitant RCT offers better outcome in terms of CCR than RT alone. Watch and wait management of rectal cancer with CCR was feasible with a well-designed follow up protocol. ?In our study we were limited by the short period of follow up and the small effective. Our results are comparable to results reported in literature.