tbuckley/cabot-search huggingface dataset:
Quality of life(QoL) outcomes including neuropathy associated scale (FACT-T) from a phase II, multicenter, randomized trial of eribulin plus gemcitabine(EG) versus paclitaxel plus gemcitabine(PG) as first-line chemotherapy for human epidermal growth factor receptor 2 (HER2)- negative metastatic breast cancer(MBC): Korean Cancer Study Group trial (KCSG BR13-11).
Authors: Ji-Yeon Kim, Seri Park, Seock-Ah Im, Sung-Bae Kim, Joohyuk Sohn, Keun-Seok Lee, Ki Hyeong Lee, Jee Hyun Kim, Young-Hyuck Im, Tae Yong Kim, Kyung-Hun Lee, Jin-Hee Ahn, Gun Min Kim, In Hae Park, Yee Soo Chae, Soo Jung Lee, Hye Sook Han, Se Hyun Kim, Kyung Hae Jung, Yeon Hee Park
Journal: Journal of Clinical Oncology (2018)

10117 Background: A phase II, multicenter, randomized clinical trial of EG and PG as first-line chemotherapy for patients with HER2-negative MBC showed that EG was less neurotoxic, but conferred a survival outcome similar to that of PG. In this study, we analyzed FACT-T questionnaires from patients participating in this clinical trial to determine their health-related Quality of life(HR QoL). Methods: Patients were randomly assigned to either EG or PG chemotherapy arm in a 1:1 ratio. QoL was assessed using the Korean version of the FACT-T questionnaire. After baseline assessment, HRQoL was assessed every 2 cycles for 12 cycles and every 3 cycles after 13 cycles of chemotherapy. The linear mixed model was used to evaluate the difference in HRQoL between the two treatments. Results: Of 118 patients, 117 patients except 1 patient in PG arm responded to the FACT-T questionnaires at baseline. Baseline FACT-T subscale QoL scores and overall QoL scores were not different between the EG and PG arms. During treatment, overall QoL scores and other FACT-T subscale scores did not differ between EG and PG arm. In terms of taxane-associated HRQoL, PG arm much increased taxane subscale scores after 2 cycles of chemotherapy compared to EG arm until the 13th cycle of treatment ( all ps < 0.05, except 11th cycle [p = 0.164]). Of taxane subscale scores, neuropathy specific subset scores were presented as similar pattern to taxane subscale scores. After 13 cycles of treatment, both groups had similarly intense symptoms. Therefore, although taxane subscale score and neuropathy specific subset score were higher in the PG arm compared to the EG arm, there was no statistical significance (p = 0.086 and p = 0.062, respectively). Conclusions: EG delayed and decreased chemotherapy induced adverse events including neuropathy compared to PG. Therefore, eribulin would be a reasonable substitute for paclitaxel as first line treatment in MBC, especially concerning neurotoxicity. Clinical trial information: NCT02263495.
The impact of the Affordable Care Act (ACA) on cancer survivorship.
Authors: Christine Leopold, Elyse Park, Larissa Nekhlyudov
Journal: Journal of Clinical Oncology (2017)

10072 Background: The ACA of 2010 has been recognized by the cancer community as an important step forward in insurance and payment reform, aiming to expand the number of insured patients, control costs and incentivize health care delivery system changes. In this review, we outline the ACA provisions relevant to cancer survivorship, provide available evidence for their impact, and offer insights for future research. Methods: We conducted a literature search in the PubMed database and grey literature. We searched the terms ‘ACA and cancer survivors’, which resulted in 17 articles and expanded the search to ‘ACA and cancer’ and found 213 articles, of which 75 were relevant for this review. We categorized the ACA provisions into three categories, 1) access to preventive care, 2) access to quality, coordinated care, and 3) coverage expansion and increased affordability. Results: Positive effects of the ACA were: an increased uptake of preventive services and cancer screening; a reduction in hospital admissions, increased guidelines concordance and generic prescribing through the implementation of cancer-specific Accountable Care Organizations; a reduction of unnecessary resource use (e.g. emergency visits) through the implementation of oncology patient-centered medical home models and decreases in costs though bundle payments. These results focus on the general population/cancer patients; specific studies targeting at the effects on cancer survivors are missing. In addition, evidence from literature showed that knowledge about the benefits of the ACA is low among childhood cancer survivors; while insurance coverage rates of cancer survivors, especially for childhood cancer survivors, increased. Conclusions: Evidence regarding the effects of the ACA on cancer survivorship care is limited, though point to greater access to preventive services and screening programs. Effects of provisions focusing on quality, coordinated care as well as coverage expansion and affordability may have beneficial effects. Whether the ACA remains or is reformed, it is critically important that decisions take into account the potential intended and unintended consequences of the ACA provisions on health outcomes and quality of life of this growing population.
Nuclear Receptors as Therapeutic Targets for Neurodegenerative Diseases: Lost in Translation
Authors: Miguel Moutinho, Juan F. Codocedo, Shweta S. Puntambekar, Gary E. Landreth
Journal: The Annual Review of Pharmacology and Toxicology (2018)

Neurodegenerative diseases are characterized by a progressive loss of neurons that leads to a broad range of disabilities, including severe cognitive decline and motor impairment, for which there are no effective therapies. Several lines of evidence support a putative therapeutic role of nuclear receptors (NRs) in these types of disorders. NRs are ligand-activated transcription factors that regulate the expression of a wide range of genes linked to metabolism and inflammation. Although the activation of NRs in animal models of neurodegenerative disease exhibits promising results, the translation of this strategy to clinical practice has been unsuccessful. In this review we discuss the role of NRs in neurodegenerative diseases in light of preclinical and clinical studies, as well as new findings derived from the analysis of transcriptomic databases from humans and animal models. We discuss the failure in the translation of NR-based therapeutic approaches and consider alternative and novel research avenues in the development of effective therapies for neurodegenerative diseases.
Oncology patients referred for cognitive training in a military treatment facility: Demographics, symptom reporting and cognitive functioning for CNS and non CNS cancers.
Authors: Katherine Sullivan, Martin A Knoll, Wendy A Law, Tejas Ranade, Brett James Theeler, Chad A. Hamilton, Yovanni Casablanca, Louis M French
Journal: Journal of Clinical Oncology (2018)

10076 Background: The Brain Fitness Center (BFC) at Walter Reed National Military Medical Center (WRNMMC) offers computer-based cognitive training, biofeedback, and brain-health classes. Originally designed for service members with traumatic brain injury, the BFC is experiencing an increase in patients with oncology-related cognitive complaints, prompting the need to better understand symptom reporting and objective cognitive functioning in this population. The goal of this analysis is to gain a better understanding of this patient population and compare the presenting symptoms and concerns of cancer patients with and without a history of central nervous system (CNS) involvement. Methods: Retrospective review and analysis of six validated symptom self-report questionnaires and objective cognitive functioning assessed by the Automated Neuropsychological Assessment Metrics (ANAM). Participants were 97 Military medical beneficiaries with cancer-related treatments referred to the BFC. Data are derived from an IRB-approved retrospective analysis protocol and were compared with published norms. Results: The average age of the study sample at time of referral was 47.3 years (SD 13.3; 49% men, 51% women), with 49% classified as CNS cancer (primary or metastatic disease) and 51% as non CNS cancer. Questionnaire results indicated moderate resilience, low adverse headache impact on daily function, reduced satisfaction with life, mild-to-moderate self-reported functional and neurobehavioral concerns, and subclinical posttraumatic stress symptoms. Average cognitive processing efficiency was poorer than demographically-matched controls ( > 1 SD below average) and was inversely associated with self-reported symptom concerns (r -.273 to -.339, p < .05). There were no differences between the CNS and non CNS groups on symptom reporting or objective cognitive performance (p > .05). Conclusions: CNS and non CNS oncology patients produce comparable symptoms and cognitive scores and demonstrate less cognitive efficiency than sex, military service, and age- matched normative groups. Limitations and clinical implications are discussed.
<i>IRS1</i> and <i>IRS2</i> polymorphisms and outcome in mCRC patients enrolled in the FIRE-3 trial.
Authors: Roel Gopez, Marta Schirripa, Wu Zhang, Shu Cao, Satoshi Okazaki, Dongyun Yang, Fotios Loupakis, Martin D. Berger, Yan Ning, Yuji Miyamoto, Mitsukuni Suenaga, Jordan David West, Diana L. Hanna, Afsaneh Barzi, Alfredo Falcone, Sebastian Stintzing, Volker Heinemann, Heinz-Josef Lenz
Journal: Journal of Clinical Oncology (2016)

11600 Background: Insulin receptor substrate (IRS)1 and IRS2 are scaffolding proteins regulating downstream signaling of Insulin Receptor(IR)/Insulin-like Growth Factor (IGF) receptors. They activate and/or regulate the PI3K and ERK pathways. IRS1 is overexpressed in CRC patients and has been associated with cancer progression and metastases development. IRS2 amplification and mutations were recently identified in tumors with increased sensitivity to anti-EGFR therapy. Methods: DNA was extracted from FFPE tissue samples of mCRC patients treated in the FIRE-3 trial. Two SNPs of IRS1 (rs1801278 and rs1801123) and 2 SNPs of IRS2 (rs1805097 and rs2289046) polymorphisms were analyzed by means of PCR and direct sequencing. The relation of IRS1 and IRS2 SNPs with PFS and OS was evaluated through Kaplan-Meier method and log-rank test in the overall population. Subgroup analyses according to RASstatus, treatment arm (FOLFIRI plus cetuximab/bevacizumab), gender and tumor site were preplanned. Cox proportional hazard regression were used in multivariate analyses. Results: 598 patients were included in the present analyses. Main patients' characteristics were the following M/F 67/33%, median age 64 range (27-79), cetuximab/bevacizumab arm 51/49%, primary tumor site right/left 22/78%. In the overall population patients with IRS1 rs1801123 C/- (N = 105) achieved a significantly worse OS compared to T/T variant carriers (N = 464) in the univariate analyses (median OS 26.4 vs 21.3 months respectively, HR = 1.32 [95%CI 1.03-1.70], p = 0.029) and in the multivariate model adjusted for sex, ECOG PS, liver only disease, primary tumor resected and stratified by treatment arm (HR = 1.31 [95%CI 1.01-1.68], p = 0.039). Similar results were observed among KRAS wt patients (N = 476) (median OS 27.6 vs 21.3 months respectively Univ analyses HR = 1.38 [95% CI 1.04-1.85], p = 0.025; Multiv model HR = 1.35 [95% CI 1.01-1.80], p = 0.041) and among RASwt patients (Univ HR = 1.39 [95%CI 1.01-1.90], p = 0.042; Multiv HR = 1.41 [95%CI 1.02-1.94], p = 0.036). Conclusions: IRS1 rs1801123 SNP may be a prognostic marker for mCRC patients. Our findings underline the importance of IGF downstream signaling pathway in RAS wt mCRC patients
Age-associated vulnerability to treatment-related late cardiotoxicity: A report from the Childhood Cancer Survivor Study (CCSS).
Authors: James Edward Bates, Qi Liu, Yutaka Yasui, Rebecca M. Howell, Daniel A. Mulrooney, Sughosh Dhakal, Wendy M. Leisenring, Daniel J. Indelicato, Todd M. Gibson, Gregory T. Armstrong, Kevin C. Oeffinger, Louis S. Constine
Journal: Journal of Clinical Oncology (2017)

10501 Background: Cardiovascular disease (CVD) is the most common non-cancer cause of death in long-term survivors of pediatric cancer. We investigated the role of age at diagnosis in modifying treatment-related late CVD risk in the CCSS population. Methods: We evaluated CTCAE grade 3 – 5 CVD events occurring ≥5 years after diagnosis in 23,465 5-year survivors of pediatric cancer diagnosed 1970-1999. We estimated the rates of developing any CVD, including coronary artery disease (CAD) or heart failure (HF). Modifications of treatment effects by age at diagnosis were analyzed using piecewise exponential models adjusting for current age, race, and smoking. Results: At a median age of 28.4 years (range 5.6 –58.3) and follow up of 20.2 years (5 – 39.3), 239 CAD and 359 HF events occurred. The cumulative incidence of CVD, CAD, and HF were 4.8% (95% CI: 4.3-5.3), 2.4% (95% CI: 2.2-2.9), and 2.5% (95% CI: 2.2-2.9) by 30 years from diagnosis. Mean cardiac radiotherapy (CRT) doses of ≥10 Gy were associated with a progressively increasing risk of CVD (10 - &lt; 20 Gy: RR 3.6, 95% CI 2.1 – 6.2, p &lt; 0.01; 20 - &lt; 30 Gy: RR 4.4, 95% CI 2.7 – 7.2, p &lt; 0.01; ≥30 Gy: RR 7.5, 95% CI 4.9 – 11.5, p &lt; 0.01) relative to those receiving no CRT. In those receiving a low mean CRT dose (0.1 - &lt; 10 Gy), younger children had higher rates of CVD (0 – 4 years: RR = 2.2, 95% CI = 1.0 – 4.6, p = 0.04; &gt; 4 - ≤13 years: RR = 2.1, 95% CI = 1.1 – 4.1, p = 0.03) compared to those &gt; 13 years, an effect not seen at higher doses. Among survivors exposed to anthracycline doses ≥250 mg/m2, those age 0 – 4 at diagnosis had increased risk of both CAD (RR = 4.9, 95% CI 1.5 – 16.3, p = 0.01) and HF (RR = 3.0, 95% CI 1.6 – 5.0, p &lt; 0.01). Cisplatin exposure ≥300 mg/m2 was associated with increased risk of any CVD (RR = 1.8, CI = 1.2 – 2.6, p &lt; 0.01), primarily attributable to increased risk of HF (RR = 2.3, 95% CI = 1.5 - 3.5, p &lt; 0.01). Conclusions: Among long-term survivors of pediatric cancer, increasing CRT dose is associated with increased risk for CVD in a dose-response relationship. Young children are at higher risk for CVD after low-dose CRT or high-dose anthracycline exposure. Cisplatin exposure significantly increases risk for CVD. These findings should inform future treatment and surveillance protocols.
Assessing the impact of early Medicaid expansion on insurance, stage at diagnosis, and survival among young adults ineligible for dependent coverage.
Authors: Justin Barnes, Kimberly J. Johnson
Journal: Journal of Clinical Oncology (2018)

6563 Background: Cancer outcomes in young adults have lagged behind other age groups, which may be related to lower rates of insurance. While some data suggest the Affordable Care Act (ACA) may improve outcomes in young adult cancer patients eligible for dependent coverage through the ACA Dependent Coverage Provision, the impact of the ACA on cancer outcomes among young adults ineligible for dependent coverage has not been well-studied. Our objective is to assess changes in insurance rates, stage at diagnosis, and survival that are associated with early (2010-2011) Medicaid expansion. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) 18 database, we identify young adults aged 27-34 years diagnosed with a first primary malignancy between 2007-2014. We utilize a quasi-experimental design, comparing expansion-related changes in insurance rates, stage at diagnosis, and survival in the intervention group (cases from states that expanded Medicaid early) to the control group (cases from other, non-expanding states) using difference-in-differences analyses applied to linear probability and Cox proportional hazards regression models. Results: A total of 47,750 cases were included in the analyses. Relative to young adults in states that did not expand Medicaid early, young adults in early expansion states had increases in Medicaid insurance (1.51 Percentage Points [PP], 95% CI = 0.15 to 2.87, p = 0.030), decreases in uninsurance (-1.99 PP, 95% CI = -3.03 to -0.95, p < 0.001), increases in early stage diagnoses (2.72 PP, 95% CI = 1.09 to 4.34, p = 0.001), decreases in late stage diagnoses (-1.34 PP, 95% CI = -2.53 to -0.16, p = 0.027), but no change in cancer-specific survival (HR: 0.95, 95% CI = 0.85 to 1.07, p = 0.41). Conclusions: For young adults ineligible for dependent coverage, early Medicaid expansion is associated with increases in Medicaid insurance rates and early stage diagnoses as well as decreases in the uninsured rate and late stage diagnoses, though evidence for a further downstream effect on survival is lacking.
Association of financial toxicity (FT) with depression, anxiety, and quality of life (QoL) in older patients with advanced cancer: An analysis of 544 patients from 31 practices in the University of Rochester NCI Community Oncology Research Program (UR NCORP).
Authors: Asad Arastu, Joseph Ciminelli, Eva Culakova, Lianlian Lei, Huiwen Xu, David W. Dougherty, Mostafa R. Mohamed, Megan Wells, Paul Duberstein, Marie Anne Flannery, Gary R. Morrow, Charles Stewart Kamen, Chintan Pandya, Jeffrey L. Berenberg, Valerie Aarne, Supriya Gupta Mohile
Journal: Journal of Clinical Oncology (2018)

e22037 Background: Financial toxicity, or the strain caused by paying for health care services, can undermine the mental health and QoL of patients (pts) in cancer care. This study examined associations of FT with depression, anxiety, and QoL in older pts with advanced cancer. Methods: This is a secondary analysis of baseline data from a Geriatric Assessment intervention study conducted by UR NCORP (URCC 13070; PI: Mohile). At baseline, pts were categorized as experiencing FT if they reported any one of the following: delaying medications due to cost, insufficient income in a typical month for food and housing, or insufficient income in a typical month for other basic needs. This definition of FT is consistent with those used in previous research. Pts also completed the Geriatric Depression Scale (GDS, score 0-15), the Generalized Anxiety Disorder-7 (GAD7, score 0-21), and the Functional Assessment of Cancer Therapy- General (FACT-G) to assess overall QoL. Associations of FT with depression, anxiety, and QoL were assessed in separate multivariate linear regression models controlling for covariates at p < 0.1. Results: Among 544 pts (mean age 77; range 70-96; 49% female), 18% (98 pts) experienced FT. In multivariate regression analysis, FT was significantly associated with all 3 outcome measures. On average, pts experiencing FT scored 0.77 points higher (p = 0.02) on the GDS (indicating greater depression severity), 1.77 points higher (p < 0.01) on the GAD7 (indicating greater anxiety severity), and 5.2 points lower (p < 0.01) on the FACT-G (indicating lower QoL). Conclusions: Older pts with advanced cancer who experience income and cost-related barriers to quality cancer care reported worse depression, anxiety, and QoL than those without FT. Given the association between FT and these measures, these 3 FT questions may help with screening to identify vulnerable older pts who may have lower QoL and be at increased risk for depression and anxiety due to FT.
An unmet challenge of primary plasma cell leukemia: A systematic review of its unique biology, efficacy of conventional, and high dose therapy.
Authors: Saad Malik, Ammad Raina, Faisal Akbar, Hafiz Muhammad Fazeel, Malik Qistas Ahmad, Vijay Kumar, Warda Faridi, Asad Malik, Pavan Tenneti, Muhammad Sardar, Amar Lal, Zabih Warraich, Abdul Rauf, Ahmad Iftikhar, Sami Warraich, Faiz Anwer
Journal: Journal of Clinical Oncology (2018)

e20048 Background: Primary plasma cell leukemia (pPCL) is rare but aggressive disease with median overall survival (mOS) of less than one year. Our aim is to review its unique biology, efficacy of available treatments and survival outcomes. Methods: Systematic review was done in accordance with PRISMA guidelines. We searched PubMed, Embase, CINAHL, Cochrane and clincaltrials.gov for studies published between 2007 – 2017. Results: From a total of 2554 studies, we included 19 (n = 1170). Median progression-free survival ranged from 1.2-21 months and median objective response rate ranged from 45.5-100%. Best treatment strategy was use of bortezomib based regimen (BBR). For induction therapy without auto-transplant (ASCT), mOS was 2.9 – 20.1 month. For induction followed by consolidation with ASCT, mOS was 7.3 – 38.1 months. For induction followed by tandem ASCT / ASCT, mOS was 34-48 months. With tandem ASCT / allo-transplant best reported mOS > 32 months (n = 4). Induction followed by ASCT and later allo-transplant patients have minimum data (n = 29), role of this strategy is still evolving and looks promising. Prognosis was favorable if patients had t(11:14), hyperploidy, normal karyotype or CD27 = ive immunophenotype. Worse prognosis was associated with hypoploidy, del(13q) and del(17p). Predictors of higher OS were treatment with proteasome containing regimen, use of ASCT and achievement of ≥ VGPR whereas predictors of poor OS were presence of t(4:14) and LDH > 300U/L. Conclusions: Novel agent combinations using proteasome inhibitors for remission induction therapy followed by single ASCT, tandem ASCT / ASCT, and ASCT / allo-transplant is superior to non-proteasome based regimens and non-transplant regimens.
Effectiveness of cytotoxic agent etoposide after biological therapy in advanced thymic tumours.
Authors: Vincenzo Damiano, Margaret Ottaviano, Pasquale Rescigno, Giuliano Palumbo, Giovannella Palmieri
Journal: Journal of Clinical Oncology (2016)

e20112 Background: The rarity and the unpredictable natural history of thymic tumors (TTs), make their management a real challenge for clinicians. Here, we describe the clinic-pathological features and clinical outcomes of seven cases of advanced heavily pretreated TTs, which responded to oral etoposide, after progressed to biological agents. Methods: Seven patients, referred to our Centre for a period of nine years, were included in this monocentric retrospective study. With a median age of 48 years (36-78), all patients (3 women and 4 men) had a diagnosis of advanced disease. According to Masaoka-Koga stage system, five patients had IVB stage disease, the other two, respectively, had III and IVA stage. Radical thymectomy was performed in III stage patient, who progressed after six months. According to WHO 2004 classification histological diagnosis of thymoma was made in five pts (B2/B3 2 pts; B3 2 pts; B2 1 pt). Thymic carcinoma (TC) was diagnosed in the last two patients. A first line platinum plus anthracycline chemotherapy was administrated. After progressed to chemotherapy, all patients started treatment with biological agents. Specifically, two patients OctreoScan positive, underwent long acting somatostatin analogues (Octreotide Lar 30 mg/4 weeks) plus prednisone (0.2 mg/kg), while five patients, in a compassionate setting, started Everolimus (10 mg/daily). After progression documented by a CT scan, all of them received oral etoposide at dose of 50 mg daily three week on/ one week off. Overall response rate and toxicities were evaluated. Results: Partial response, according to RECIST criteria 1.1., was achieved in five patients (72%). Two patients with TC progressed after at least 3 cycles of therapy. G1 Nausea was registered in 3 cases, no hematological toxicity has been detected. Four patients are still on treatment with no relevant toxicities with a median of 12 cycles. One patient died owing to complication of surgery for acute abdomen. Conclusions: Our experience of long lasting management of advanced relapsed TET, shows as the histological diagnosis could help clinicians for the best therapeutic choice. Oral etoposide is a well tolerated and effective cytotoxic agent. Further studies are needed.