tbuckley/cabot-search huggingface dataset:
Associations between cancer patients' advance care and financial planning and surviving spouses' financial well-being.
Authors: Alexi A. Wright, Nancy Lynn Keating, Lauren Hersch Nicholas
Journal: Journal of Clinical Oncology (2017)

6567 Background: The “financial toxicity” associated with cancer treatment, including high out-of-pocket expenses and lost earnings, may have lasting financial effects for surviving spouses. Although advance care planning (ACP) is used as a cancer quality metric, the value of financial planning is unknown. Methods: We examined associations between cancer patients’ written ACP and financial planning (will) and surviving spouses’ financial well-being using prospective, nationally representative data from the 2004-2014 waves of the Health and Retirement Study. We assessed change in household, non-housing (financial) wealth, including debt, among 962 surviving spouses of cancer decedents. Because wealth varies widely in the US, we fit multivariable quantile regression models at the 25 th , 50 th , and 75 th percentiles to examine associations between cancer decedents’ ACP, financial planning, and wealth, adjusting for sociodemographic characteristics. Results: Among cancer decedents, 33% completed both ACP and a will, 27% only a will, 10% only ACP, and 30% neither. The median wealth of surviving spouses was $22,309 (25 th percentile = $0, 75 th percentile = $134,238). Among spouses of cancer decedents in the 25 th percentile of wealth before death, completion of ACP and a will was associated with $5,348 (95% CI = $1,172-$9,523) more financial wealth after death compared with no planning. Use of ACP and a will was also associated with $46,851 (95% CI = $2,810-$90,891) more financial wealth at the 75 th percentile. There were no differences in the wealth of surviving spouses after death between patients who completed only a will, only ACP, or no planning (Ps &gt; .09). Conclusions: Completion of ACP and financial planning was associated with greater wealth among both affluent and non-affluent surviving spouses compared with no planning. Efforts to sensitively incorporate financial planning into cancer patients’ care have the potential to improve surviving family members’ financial well-being.
A Prospective Adaptive Utility Trial to Validate Performance of a Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer in Patients with Prostate-specific Antigen 2–10 ng/ml at Initial Biopsy
Authors: James McKiernan, Michael J. Donovan, Eric Margolis, Alan Partin, Ballentine Carter, Gordon Brown, Phillipp Torkler, Mikkel Noerholm, Johan Skog, Neal Shore, Gerry Andriole, Ian Thompson, Peter Carroll
Journal: European Urology (2018)

Discriminating indolent from clinically significant prostate cancer (PCa) in the initial biopsy setting remains an important issue. Prospectively evaluated diagnostic assays are necessary to ensure efficacy and clinical adoption. Performance and utility assessment of ExoDx Prostate (IntelliScore) (EPI) urine exosome gene expression assay versus standard clinical parameters for discriminating Grade Group (GG) ≥2 PCa from GG1 PCa and benign disease on initial biopsy. A two-phase adaptive clinical utility study (NCT03031418) comparing EPI results with biopsy outcomes in men, with age ≥50 yr and prostate-specific antigen (PSA) 2–10 ng/ml, scheduled for initial prostate biopsy. After EPI performance assessment during phase I, a clinical implementation document (ie, CarePath) was developed for utilizing the EPI test in phase II, where the biopsy decision is uncertain. Performance evaluation of the EPI test in patients enrolled in phase I and publication of a consensus CarePath for phase II. In a total of 503 patients, with median age of 64 yr, median PSA 5.4 ng/ml, 14% African American, 70% Caucasian, 53% positive biopsy rate (22% GG1, 17% GG2, and 15% ≥ GG3), EPI was superior to an optimized model of standard clinical parameters with an area under the curve (AUC) 0.70 versus 0.62, respectively, comparable with previously published results (n = 519 patients, EPI AUC 0.71). Validated cut-point 15.6 would avoid 26% of unnecessary prostate biopsies and 20% of total biopsies, with negative predictive value (NPV) 89% and missing 7% of ≥GG2 PCa. Alternative cut-point 20 would avoid 40% of unnecessary biopsies and 31% of total biopsies, with NPV 89% and missing 11% of ≥GG2 PCa. The clinical investigators reached consensus recommending use of the 15.6 cut-point for phase II. Outcome of the decision impact cohort in phase II will be reported separately. EPI is a noninvasive, easy-to-use, gene expression urine assay, which has now been successfully validated in over 1000 patients across two prospective validation trials to stratify risk of ≥GG2 from GG1 cancer and benign disease. The test improves identification of patients with higher grade disease and would reduce the total number of unnecessary biopsies. It is challenging to predict which men are likely to have high-grade prostate cancer (PCa) at initial biopsy with prostate-specific antigen 2–10 ng/ml. This study further demonstrates that the ExoDx Prostate (IntelliScore) test can predict ≥GG2 PCa at initial biopsy and defer unnecessary biopsies better than existing risk calculator's and standard clinical data.
Rhabdomyosarcoma (RMS) in adults: Histologic subtypes and overall survival with actinomycin-based chemotherapy vs doxorubicin-based chemotherapy.
Authors: Alia Vang, Steven Ian Robinson, Scott H. Okuno
Journal: Journal of Clinical Oncology (2017)

11073 Background: RMS typically occurs in children. Vincristine, Actinomycin and Cyclophosphamide (VAC) based chemotherapy is the current standard. Limited data exist on the frequency of the histologic subtypes and optimal chemotherapy regimen for the treatment of adult patients with RMS. Methods: We retrospectively identified patients ≥18 years with RMS seen at our institution from 2000-2015. The analysis was performed with JMP statistical software. Results: We identified 73 patients, with a median age of 51 (range 18-85 years). The majority of patients were male (40 of 73) and presented with localized disease (59 of 73). Histologic subtypes were as follows: 32% embryonal (E), 27% alveolar (A), 36% pleomorphic (P), and 6% variants (V) (botryoid and spindle cell/sclerosing). The median overall survival (OS) for patients with localized disease was 16.2 months and metastatic disease 9 months. The median OS for patients with localized disease treated with VAC was 20.3 months (4A, 7E, 3P) and VDC (vincristine doxorubicin cyclophosphamide) was 14.1 months (3A, 3E, 2P). For those with localized disease treated with a VAC/actinomycin-based chemotherapy had a median OS of 19.5 months (4A, 9E, 3P) and with a VDC/doxorubicin-based chemotherapy had a median OS of 15.9 months (8A, 5E, 13P, 2V). Conclusions: Adult patients with RMS have an even distribution among the histologic subtypes. Given the small, unbalanced number of patients in each histologic subtype treated with VAC/actinomycin-based or VDC/Doxorubicin-based regimens, the overall survival benefit favoring the use of VAC/actinomycin-based is hypothesis generating and confirmatory studies are needed to truly determine the optional regimen for adult patients with RMS.
Mediastinal germ cell tumors and development of secondary leukemia and solid tumors.
Authors: Nicholas A Madden, Bryan M Rabatic, David Zaenger, Joseph A Marascio, Edward M Marchan, Byron G Dasher, William D Martin, Jed W Howington, Maryam Aletan, John G Stewart, Mahboubeh Pishgou, Ahmad Amoush, Catherine L Ferguson, Feng-Ming (Spring) Kong, Waleed F Mourad
Journal: Journal of Clinical Oncology (2016)

e16043 Background: Retrospective studies have shown a correlation between mediastinal germ cell tumors (MGCT) and development of AML. Primary treatment for MGCTs is multiagent chemotherapy, which can also be associated with AML. MGCTs have not been associated with increased risk of other solid tumors. Due to the rarity of these tumors, the risk of secondary malignancy and subsequent survival are not fully defined. Methods: The SEER database was queried for mediastinal germ cell tumors by including all patients from 1973-2012 with ICD-O3 codes 9061/3 through 9102/3 and “primary site labeled” variable in SEER codes C38.1-38.3 and C38.8. An MP-SIR session was utilized to determine secondary malignancies in this cohort. Observed-to-expected ratios (O/E) were calculated with no latency period and with a latency period of 5 years to evaluate for early and late cancers. P < 0.05 was used to determine statistical significance. Results: 1113 patients were identified; patients were predominantly male (92%), white (82%), and in their 30s or younger (78%). 76% were non-seminomatous tumors. 29 total secondary malignancies were identified (O/E 2.34), with significant elevations in respiratory (O/E 4.14, n = 6) and hematopoietic cancers (O/E 6.47, n = 9). One case of nodal NHL and 8 cases of AML (O/E 78.47) were identified. All cases of AML were associated with non-seminomatous MGCTs. 5 cases of AML developed within 0-6 months after diagnosis of MGCT (O/E 1206). Two additional cases were diagnosed with a latency period of 6-11 months and 24-35 months. All patients who developed AML died from the disease, with median survival less than 6 months. Risk of developing AML was highest within 5 years of diagnosis (O/E 271), remained elevated between 5-10 years after diagnosis (O/E 54), before normalizing after 10 years. Increased risk of respiratory malignancy was only present in patients treated with radiation (O/E 5.10). Conclusions: Non-seminomatous MGCTs are associated with an increased risk of secondary AML. The highest risk for AML is within 6 months of diagnosis of MGCT. An increased risk of respiratory cancers is also reported in patients who received radiation therapy. Close surveillance for secondary malignancy is needed though prognosis is very poor.
Characteristics of local immunity factors in esophageal cancer with varying degrees of differentiation.
Authors: Oleg Ivanovich Kit, Elena Yurievna Zlatnik, Inna Arnoldovna Novikova, Olesya N. Selyutina, Galina I. Zakora, Elena Bondarenko, Aleksey Yurievich Maksimov, Evgeniy N. Kolesnikov, Vladimir Trifanov, Leonid V. Kharin, Alexander V. Snezhko, Petr Gabrichidze, Adlan Lechaevich Bazaev
Journal: Journal of Clinical Oncology (2016)

e15518 Background: The purpose of the study was to evaluate parameters of the local immunity in patients with esophageal cancer with varying degrees of differentiation. Methods: Tissues of tumor and peritumoral zone obtained during surgery from 25 patients with esophageal cancer (6 women and 19 men aged 40-77 years) mainly affecting upper thoracic (1 patient), mid thoracic (12) and lower thoracic esophagus (11) were studied. Histological examination showed squamous cell carcinoma: 7 patients without keratinization and 18 with it. 8 patients had poorly differentiated tumor, 12 – moderately differentiated, 5 – well-differentiated one. Lymphocyte subpopulations were determined in tissue homogenates using flow cytometer FACSCantoII (BD) with panel of antibodies T-, B-, NK (CD45, CD3, CD4, CD8, CD19, CD16/56), levels of NKT (CD3+CD16/56+) and DN (CD3+CD4-CD8-) were calculated; quantitative content of regulatory T (T-regs) cells (CD4+CD25+CD127dim) was evaluated. The results were expressed in percentage from the total lymphocyte content, and for T-regs – in percentage from CD3+CD4+ cells. Results: Significant differences in lymphocyte subpopulations were found between tumor and non-malignant tissues. Content of CD3+CD4+ cells in tumor exceeded that in resection line (47.8±6.06 vs 23.6±4.26%), as well as content of T-regs (19.1±2.8 vs 3.8±1.1%), while levels of other subpopulations did not differ. Well-differentiated tumors (G1) in comparison with poorly differentiated ones (G3) showed significantly higher levels of mature T-lymphocytes (CD3+) and especially CD3+CD4+ cells that amounted for 51.0±2.7% in G1, 46.9±5.8% in G2 and 25.8±6.8% in G3 (р < 0.05). Levels of T-regs in tumors did not differ significantly and were high in all tumor grades. Content of NKT-lymphocytes was higher in poorly differentiated G3 tumors (9.3±2.1% vs 4.1±1.1% in G2 and 2.8±0.7% in G1; р < 0.05). Levels of CD3+CD8+ and B-cells were similar in all degrees of tumor differentiation. Conclusions: Tissues of esophageal tumors are characterized by a higher local content of CD3+CD4+ lymphocytes and Т-regs in comparison with adjacent non-malignant tissue. CD3+CD4+ content was higher in well-differentiated tumors.
Abstract 10780: New Oral Anticoagulants and the Risk of Intracranial Hemorrhage-Insights From a Traditional and Bayesian Meta-analysis and Mixed-Treatment Comparison of Randomized Trials
Authors: Saurav Chatterjee, Ahana Roy, Partha Sardar, Giuseppe Biondi-Zoccai, Dharam J Kumbhani
Journal: Circulation (2013)

Objective: Randomized studies have shown a decreased risk of intracranial hemorrhage (ICH) with use of novel oral anticoagulants (NOACs). We performed a meta-analysis to quantitatively assess the rates of ICH. Methods: MEDLINE, CENTRAL, CINAHL and EBSCO databases, supplemented with conference abstracts, were searched up to December 1, 2012, with no language restriction. NOACs were pooled to perform a comparison in both traditional ‘Frequentist’ as well as ‘Bayesian’ random effects models using ‘vague’ priors and Markov Chain Monte Carlo simulation with Gibbs sampling, calculating pooled odds ratios (ORs) and associated 95% confidence intervals (CIs); as well as number-needed-to-treat (NNT) and 95% credible intervals (CrIs) for the Bayesian analysis. Results: 6 studies (dabigatran1, rivaroxaban2, apixaban3) enrolling a total of 57,491 patients were included for analysis. NOACs significantly reduced the risk of ICH against all comparators (OR 0.49, 95% CI 0.36-0.65). All the 3 individual drugs reduced the r...
A bayesian network meta-analysis of different agents or regimens as second-line treatment for SCLC.
Authors: Qihua He, Jianrong Zhang, Jianfei Shen, Jiaxi He, Wenhua Liang, Jianxing He
Journal: Journal of Clinical Oncology (2016)

e20087 Background: Current clinical evidence has indicated several effective second-line regimens in patients with relapsed/refractory small cell lung cancer (SCLC). We sought to perform a network meta-analysis to comprehensively compare these regimens. Methods: Electronic databases were searched for eligible studies. The primary endpoint was to compare the progression free survival (PFS) and overall survival (OS) which were estimated by hazard ratio (HR). Bayesian networks were built based for overall population, and prior chemotherapy-sensitive or -insensitive population respectively. Single agent i.v. topotecan (TPT) was used as a common comparator. Results: 10 studies involving 1,613 patients with SCLC were incorporated to generate the networks. The relative HRs for PFS of amrubicin, TPT+aflibercept, cabazitaxel, oral TPT compared with TPT was 0.80 (0.68-0.94), 0.71 (0.56-0.90), 2.16 (1.55-3.01) and 1.15 (0.93 -1.43) respectively in overall population. The HRs for PFS of amrubicin, TPT+aflibercept, cabazitaxel compared with TPT was 0.45 (0.38-0.53), 0.76 (0.51-1.15) and 1.88 (1.20-2.95) respectively in prior chemotherapy-sensitive SCLC. When analyzed the PFS in patients with prior chemotherapy-insensitive SCLC, the data was insufficient. For OS , the HRs of amrubicin, cabazitaxel, oral TPT, and CAV compared with TPT was 0.92 (0.77-1.10), 1.57 (1.10-2.23), 0.90 (0.71-1.14), 0.93 (0.72-1.21) respectively in all SCLC patients; the HRs of amrubicin, topotecan+aflibercept, cabazitaxel compared with TPT was 0.96 (0.76-1.21), 1.07 (0.83-1.38),1.44 (0.86-2.42) respectively in SCLC patients who were sensitive to previous first-line chemotherapy; the HRs of amrubicin, TPT+aflibercept, irinotecan, paclitaxel/docetaxel, cabazitaxel compared with TPT was 0.77 (0.59-0.99), 0.88 (0.56-1.39),0.69 (0.55-0.86),1.28 (0.65-2.53),1.51 (0.93-2.44) respectively in prior chemotherapy-insensitive patients. Conclusions: From the extensive network estimation, amrubicin, and the regimen of topotecan+aflibercept seem to be superior to topotecan alone in terms of PFS. However, when targeted on OS, there is no strong evidence supporting any advantage for one second-line option over another.
A randomized, multicenter phase 2 study of DSP-7888 dosing emulsion in combination with bevacizumab (Bev) versus Bev alone in patients with recurrent or progressive glioblastoma.
Authors: John Frederick De Groot, Timothy Francis Cloughesy, Marshall W. Pitz, Yoshitaka Narita, Takeshi Nonomura
Journal: Journal of Clinical Oncology (2018)

TPS2071 Background: Glioblastoma (GBM) is the most frequently diagnosed high-grade glioma with an incidence of 3-4/100,000 in the US. Although treatments have improved, median survival remains 15–18 months for newly diagnosed patients. DSP-7888 is an investigational peptide cancer vaccine comprised of peptides derived from the Wilms’ Tumor 1 (WT1) protein, with immunomodulating and antineoplastic activities. DSP-7888 may induce a WT1-specific cytotoxic T-lymphocytes against WT1-expressing tumor cells in HLA-A*02:01+, HLA-A*02:06+, and HLA-A*24:02+. DSP-7888 may induce a helper T-lymphocyte–mediated immune response against WT1-expressing tumor cells. Methods: This phase 2, active-controlled, multicenter, open-label randomized study (NCT03149003; WIZARD201G) is randomizing patients with recurrent or progressive GBM 1:1 to treatment with DSP-7888 + Bev or Bev alone. A screening phase of ≤28 d determines eligibility. DSP-7888 is administered intradermally at 10.5mg every 7 d (±1 d) for 5 doses (induction phase), then every 14 d (±3 d) for 6–15 doses (consolidation phase), then every 28 d (±7 d) for each additional dose (maintenance phase). Bev is administered every 14±3 d IV at 10mg/kg. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, response rate, and 12-month survival. Safety will be evaluated based on adverse events (AEs) recorded at each visit, physical examinations, and laboratory test results. The severity of AEs or abnormal laboratory results will be based on the CTCAE V4.03. About 200 patients will be enrolled. The study has 2 parts. In part 1, 3 patients are to receive DSP-7888 + Bev in a single-arm manner. If no patients experience a dose limiting toxicity (DLT), the study proceeds to part 2. If ≥1 patient experiences DLT, 3 more patients will be treated in the same manner. If ≥1 patient again experiences a DLT, the dose is reduced to 3.5mg. In part 2, new patients are randomized to one of the 2 treatment arms. Treatment continues in the absence of clear progression, clinical neurologic deterioration, or until 150 deaths have occurred. Study funding: Boston Biomedical, Inc. Clinical trial information: NCT03149003.
Efficacy of PD-1 and PD-L1 inhibitors in older adults: A meta-analysis.
Authors: Rawad Elias, Anita Giobbie-Hurder, Osama E. Rahma
Journal: Journal of Clinical Oncology (2017)

e21544 Background: Immune checkpoint inhibitors (ICIs) have a promising activity in variety of malignancies however little is known regarding their efficacy and toxicity profile in older adults (≥65 yo). Accordingly, we performed a meta-analysis of published trials using anti-PD-1 or PD-L1 to define the activity of these agents in this subset of patients. Methods: We conducted a search using PubMed and Web of Science databases for randomized controlled trials (RCTs) of PD-1 and PD-L1 inhibitors including nivolumab (N), pembrolizumab (P), and atezolizumab (A). We then identified the studies that reported a subgroup analysis of overall survival (OS) based on an age cutoff. Results: We identified a total of 17 RCTs that compared N, P and A to chemotherapy or targeted therapy. Out of those trials only 9 reported hazard ratio (HR) based on age and were included in this meta-analysis. These trials treated a total of 5033 patients including 2315 patient ≥65 yo (46%). The overall estimated, random-effects hazard ratio (HR) for death was 0.69 with 95% CI of 0.63 -0.74 (p &lt; 0.0001) in the general population favoring ICIs. Based on the selected trials, there was evidence of a 31% reduction in the hazard of death with PD1/PDL1 inhibitors compared with chemo/targeted therapy. This OS benefit persisted when the analysis was done based on disease type (NSCLC or others) or the drug target (PD-1 or PD-L1). Analysis based on age cutoff of 65 yo showed that the efficacy of PD-1 and PD-L1 inhibitors did not vary for older or younger patients. The overall estimated random-effects HR was 0.64 with 95% CI of 0.54 -0.76 in patients ≥65 yo vs. 0.68 with 95% CI of 0.61-0.75 in patients &lt; 65 yo. Data regarding toxicity based on age was available only for 3 trials. The rate of grade 3-4 toxicities was comparable between the 2 groups (45-50% in patients ≥ 65 compared to 37.1-50% in patients &lt; 65). Conclusions: PD-1 and PD-L1 inhibitors efficacy using N, P or A is comparable in older and younger adults when using an age cutoff of 65 years. Future ICIs trials should report efficacy and toxicity based on age.
The mutational landscape of circulating cell free DNA in patients with colorectal adenoma and carcinoma.
Authors: Ying Hu, Hao Guo, Yawei Chen, Yanhui Chen, Ling Lan, Jian Li, Henghui Zhang
Journal: Journal of Clinical Oncology (2018)

e15662 Background: This study was designed to explore the plasma cell free DNA (cfDNA) mutation profile in the pathological progression of colorectal cancer. In addition, we aimed to illustrate the difference mutation profile among the left-sided colon, right-sided colon, and rectal carcinoma. Methods: Tumor tissue and matched blood samples were collected from Henan Provincial People’s Hospital between March 2016 and January 2017.This cohort included 9 cases of colon polyps, 18 cases of colon adenoma, 26 cases of colon cancer, 24 cases of rectal cancer. Tissue DNA, the plasma cfDNA and leukocytes DNA were isolated. The mutation profile of plasma cfDNA in the process of adenoma-to-carcinoma was sequenced using a modified cancer gene panel. Results: The plasma cfDNA concentrations and somatic mutation burden of colon carcinoma were significantly higher than those in colon polyp and adenoma group. The tumor mutation burden (TMB) in tissue DNA is positively correlated with the TMB in plasma cfDNA. A biomarker combination including the CEA protein level, the plasma cfDNA concentration, and cfDNA mutation burden achieved an area of 0.80 under the receiver operation characteristic curve for diagnosis of CRC. The diagnosis power of the combination model was superior to that of CEA alone. Furthermore,the somatic DNA alteration landscapes are different among the left-sided, right-sided, and rectal cancer. Compared with the life-sided colon, the right-sided colon cancer tumor tissue harbors more gene mutations. And the TMB value of the right-sided colon cancer was significantly higher than those in the life-sided colon and rectal-sided colon cancer (P < 0.05). Conclusions: The somatic mutations of plasma cfDNA may be potential biomarkers for diagnosis colorectal cancer. Compared with left-sided colon, the somatic mutations of right-sided colon cancer involved more genes and pathways.