tbuckley/cabot-search huggingface dataset:
Characteristics of the Suscro Distress Inventory (SDI) for cancer survivors.
Authors: Matthew Francis Hudson, Regina A Franco, Kerri Susko, Elizabeth Crowley, Candace Sprouse, McCormick Douglas, Perkins Leann, Julia Yates, Leighton Patricia, Stephanie Hoopes, Kathleen Brant, Mark Allen O'Rourke
Journal: Journal of Clinical Oncology (2016)

e21541 Background: There remains a need for a concise tool to screen both globally and in the various domains of distress experienced by cancer survivors. The Suscro Distress inventory (SDI) was developed to address the need for a robust but brief screening tool to be used in a high volume cancer center. Methods: The SDI is a self-administered pencil and paper questionnaire with 12 questions answered with a Likert scale of 0 to 4, with a range of scores from 0, indicating low distress, to 48, indicating very high distress. It is given to people newly diagnosed with cancer at their first visit to the cancer center. The questions, derived from stakeholder input, address mood, anxiety, financial worry, fatigue, isolation, purpose and meaning, appearance, intimacy, sleep, support, diet and discomfort. Auditing of adherence to the use of the SDI in 2015 led to the collection of 200 completed SDI forms. The forms were entered into a RedCAP database and analyzed by SPSS. Results: SDI scores ranged from 0 to 46, with an average score of 12.7 (SD = 9.4). The rounded quartiles were 0 to 5, 6 to 9, 10 to 17, and 18 to 46. A priori severity categories were determined. The distribution was No Distress (0-7) 38%, Low (8-13) 25.5%, Medium (14-18) 13.5%, High (19-27) 13%, and Very High (28-48) 10%. Chronbach’s alpha was .871. A single principle component accounted for 46% of the variance in the SDI. Conclusions: The SDI differentiated well between respondents. It labeled 36.5% as medium or higher distress. The alpha estimate indicates that the inventory items measure the same construct. The principle component analysis suggests that multiple dimensions measured in the questionnaire are subsumed by a general construct. These features of the SDI suggest that a validation study is indicated.
A randomized phase III trial of capecitabine with or without irinotecan driven by UGT1A1 in neoadjuvant chemoradiation of locally advanced rectal cancer (CinClare).
Authors: Ji Zhu, Xinchen Sun, Tao Zhang, Anwen Liu, Yuan Zhu, Jianhui Jia, Yaqun Zhu, Shisheng Tan, Juying Zhou, Chen Zhang, Xin Wang, Gang Cai, Bo Luo, Junxin Wu, Jialin Yang, Zhen Zhang
Journal: Journal of Clinical Oncology (2017)

TPS3632 Background: Irinotecan is an effective drug for rectal cancer. Early small sample size trials have assessed the addition of irinotecan to standard CRT with fluoropyrimidines in neoadjuvant phase of locally advanced rectal cancer, in which pCR rates varied from 13.7 to 37%. ARISTOTLE trial, a multicentre UK-based phase III trial, will complete recruitment in autumn 2016. However, all patients in case group were prescribed with weekly irinotecan dose of 60mg/m 2 guided by UGT1A1*28 6/6 and 6/7 genetypes in neoadjuvant chemoradiation. Therefore, this phase III trial was designed to confirm the potential improvement in outcomes seen with the addition of irinotecan to CRT. Methods: Eligible patients are randomly allocated to either radiotherapy 50 Gy with concurrent capecitabine, followed by a cycle of capecitabine and oxaliplatin two weeks after the end of CRT (Control arm) or radiotherapy 50 Gy with concurrent capecitabine and irinotecan, followed by a cycle of capecitabine and irinotecan (Case arm). Capecitabine is prescribed with 825mg/m 2 The primary end point is ypCR. The hypothesis is to increase ypCR from 12% in the control group to 25% in the case group. To detect such a difference, with alpha = 0.05 (two-tailed) and belta = 0.15, 360 randomly assigned patients are required. Secondary end points are toxicities, surgical complications, local control, progression-free survival and overall survival. Clinical trial information: NCT02605265.
Psychological and educational outcomes among adolescent survivors of wilms tumor: A report from the Childhood Cancer Survivor study.
Authors: Rebecca Hope Foster, Robert J. Hayashi, Mingjuan Wang, Wei Liu, Caroline Mohrmann, Rebecca M. Howell, Susan A Smith, Todd M. Gibson, Deo Kumar Srivastava, Daniel M. Green, Kevin C. Oeffinger, Wendy M. Leisenring, Leslie L. Robison, Gregory T. Armstrong, Kevin R. Krull, Kristina K. Hardy
Journal: Journal of Clinical Oncology (2017)

10049 Background: Little is known about psychological and educational problems experienced by adolescent survivors of Wilms tumor (WT), including the impact of treatment exposures and chronic health conditions. Methods: Parent-reports from the Childhood Cancer Survivor Study were analyzed for 666 adolescent survivors of WT (Mean[SD] age at survey = 15.3[1.65] years; age at diagnosis = 2.8[1.77] years) and 698 siblings (15.4[1.66] years). Adjusting for race and household income, survivors were compared to siblings on the Behavior Problem Inventory and educational services. Among survivors, therapeutic exposures and chronic medical conditions (CTCAE 4.03 coding) were examined via multivariable log binomial regression adjusting for sex, race, income and age at diagnosis to calculate adjusted Relative Risk (aRR) and 95% confidence intervals (CI). Results: Compared to siblings, survivors were more likely to use psychoactive medication (9.4 vs. 5.1%, p = .0002) or be in special education for learning problems, inattention, and/or low test scores (19.1 vs. 11.1%, p = .003) but had similar rates of depression/anxiety, headstrong behavior, inattention, social withdrawal, and antisocial behavior (p’s &gt; .05). Survivors who received radiation therapy (RT) to the abdomen (aRR 1.64, CI 1.03-2.61) or abdomen and chest (aRR 1.95, CI 1.16-3.26) were more likely to be in special education for any reason than those without RT. Those with grade 2-4 cardiovascular conditions were more likely to have anxiety/depression (aRR 2.04, CI 1.26-3.30), headstrong behavior (aRR 1.95, CI 1.30-2.93), or inattention (aRR 1.58, CI 1.04-2.42) compared to survivors with grade 0/1 conditions. Survivors were more likely to be in special education if they had problems with antisocial behavior, anxiety/depression, headstrong behavior, inattention or social withdrawal (p’s &lt; .05). Conclusions: Psychological intervention may be needed for adolescent survivors of WT treated with RT to the abdomen or abdomen and chest or with higher grade cardiovascular conditions. These survivors are more likely to experience behavioral and emotional problems, which in turn increases risk for placement in special education.
Frailty and inflammatory markers in older adults with cancer.
Authors: Tomohiro F. Nishijima, Allison Mary Deal, Grant Richard Williams, Emily Jean Guerard, Kirsten A Nyrop, Hyman B. Muss
Journal: Journal of Clinical Oncology (2016)

10039 Background: The relationship between frailty and systemic inflammation has not been well studied among older adults with cancer. Recently, simple and readily available inflammatory markers, such as neutrophil lymphocyte ratio (NLR; Templeton, 2014) and lymphocyte monocyte ratio (LMR; Nishijima, 2015) have been shown to have robust prognostic value in various cancers. Therefore, we examined the association between frailty and these novel biomarkers in older adults with cancer. Methods: We conducted cross-sectional analyses of data derived from the Carolina Seniors Registry (CSR), a registry (NCT01137825) to collect Geriatric Assessments (GA) on older adults (+65) with cancer. We included patients in the CSR who had a GA and CBC with differential before initiation of therapy. The primary outcome was frailty, determined using the 32-item frailty index (FI) [ASCO 2015, abstr 9535]. The secondary outcomes were physical function scale, and instrumental activity of daily living (IADL). Spearman’s correlation and multivariable logistic regression were used to evaluate the associations. Results: Of 121 total patients, the median age was 74, 88.4% white, 81.8% female, 90.9% had at least a high school education, 49.6% married, and 61.2% had a breast cancer diagnosis. Overall 52.3% were robust, 24.8% were pre-frail, and 22.9% were frail based on FI. There was a significant positive correlation between FI and NLR (r = 0.21, p = 0.042) and a significant negative correlation was found between FI and LMR (r = -0.23, p = 0.027). On multivariable analysis, patients in the top tertile of NLR ( > 4.1) had an odds ratio of 3.94 (95% CI = 1.16 - 13.34, p = 0.027) for frail/pre-frail status, adjusting for covariates significantly associated with FI such as age, education and marital status. Higher NLR (r = -0.26, p = 0.013) and lower LMR (r = 0.25, p = 0.018) were in significant association with a lower IADL score. Higher NLR was significantly related to a lower physical function score (r = -0.23, p = 0.031). All correlations were in the directions as hypothesized. Conclusions: This study provides evidence linking frailty and inflammation in older adults with cancer. These biomarkers warrant further investigation in larger studies with a special focus on their utility in clinical practice.
P02.14 Tumour Treating Fields (TTFields) demonstrate variable efficacy on high-grade paediatric brain tumour cell lines in a frequency-dependent manner
Authors: J Branter, M Estevez Cebrero, R Grundy, S Basu, S Smith
Journal: Neuro-Oncology (2018)

The EF-14 trial of the Optune system which utilises Tumour Treating Fields (TTFields) to disrupt dividing cells has shown survival benefit in adult Glioblastoma multiforme (GBM) patients. These results have given credence to the addition of alternating electric fields to existing conventional therapy regimes for brain tumour patients. Here we present data showing how TTFields may inhibit division of our paediatric GBM, Medulloblastoma and Ependymoma cell lines. We delivered TTFields over a range of clinically relevant frequencies (100-400kHz) to our panel of high grade paediatric cell lines using the Inovitro system. The effects of TTFields on cell viability was assessed using metabolic tests and cell count, and cell cycle analysis was performed using flow cytometry. TTFields was combined with paclitaxel and cell viability was measured to assess efficacy of the combinational approach. Gene expression analysis following TTFields treatment was performed via Affymetrix microarray. TTFields have significant efficacy on all of our cell lines in a frequency-dependent manner. Cells treated with TTFields exhibited up to 75% slower growth rates when re-seeded and compared to untreated cells. Cell cycle analysis revealed that TTFields treated cells have significant accumulation in the G2/M phase relative to control cells. The efficacy of TTFields may be significantly increased with the addition of the paclitaxel. The effects of TTFields treatment on gene expression will be discussed. TTFields treatment has shown significant efficacy against our panel of paediatric GBM, Medulloblastoma and Ependymoma cell lines. The optimal frequencies determined for some of our cell lines fall outside the 200KHz range used in the clinic for adult GBM patients.
A phase I trial of ipilimumab (ipi) in patients (pts) with myelodysplastic syndromes (MDS) after hypomethylating agent (HMAs) failure.
Authors: Amer M Zeidan, Hanna Knaus, Tara M. Robinson, Joshua F. Zeidner, Amanda L. Blackford, David Rizzieri, Mark G. Frattini, Moshe Yair Levy, Mark A. Schroeder, Anna K. Ferguson, Katherine Sheldon, Amy Elizabeth Dezern, Ivana Gojo, Steven Gore, Howard Streicher, Leo Luznik, Amy Duffield, B. Douglas Smith
Journal: Journal of Clinical Oncology (2017)

7010 Background: Pts with HR-MDS after HMA failure have a poor overall survival (OS) of &lt; 6 months. Immune escape is associated with resistance to HMAs in MDS. We hypothesized that CTLA-4 blockade in these pts would be tolerable and lead to clinical responses. Methods: This investigator-initiated, CTEP-sponsored, multi-center phase 1b study enrolled pts after failure of HMAs. In dose-escalation, ipi monotherapy was given at 2 dose levels (DL): 3 and 10mg/kg. Four doses (every 3 weeks) were administered followed by a maintenance phase (4 doses every 3 months) for non-porgressors. Toxicities and responses were evaluated with CTCAE4 and IWG2006 criteria, respectively. OS was estimated using the Kaplan-Meier method. The impact on T-cells were studied by flow cytometry and TCR sequencing. Results: 29 pts from 7 centers were enrolled. Mean age (SD) was 67 (8) years. Most had IPSS high/int-2 (55%), 45% had int-1. Three of 6 pts in DL1 and 4 of 5 pts in DL2 experienced grade [G]2-4 immune-related adverse events [IRAEs] that were reversible with drug discontinuation or systemic steroids. The DL1 (3mg/kg) was expanded with no G2-4 IRAEs reported in the 18 additional pts. A total of 15 deaths occurred due to disease progression or other complications but none attributed to ipilimumab. In total, 52% received all 4 induction doses, and 24% received ≥1 maintenance dose. Best objective responses were 2 marrow complete responses (mCR, 7%). Prolonged stable disease (PSD) for ≥46 weeks occurred in 6 pts (21%) and for ≥54 weeks in 3 pts (10%). Five pts (17%) subsequently underwent allogeneic transplantation (alloSCT) without evidence of excessive toxicity. Median OS (censoring at alloSCT) was 294 days (95%CI, 240-671+) and 400 days (95%CI, 240-671+) for those who received maintenance (n = 7). Pts who achieved PSD and mCR had significantly increased expression of ICOS, a marker of T-cell activation. Conclusions: Immune checkpoint blockade with ipi is tolerable and can lead to PSD/mCR in a proportion of pts. However, ipi monotherapy efficacy is limited after HMA failure and combination-based approaches should be considered. Increased frequencies of ICOS expression might predict clinical benefit. Clinical trial information: NCT01757639.
Hedgehog inhibition impaired platinum response in high-grade serous ovarian cancer harboring high hedgehog ligand expression and mTOR pathway activation.
Authors: Gwo Yaw Ho, Elizabeth Lieschke, Elizabeth Kyran, Kristy Shield-Artin, Olga Kondrashova, Holly Barker, Robert Hollian, Aurelie Cazet, Thuan Phuong, Alex Swarbrick, Orla McNally, David Bowtell, Matthew Wakefield, Clare L. Scott
Journal: Journal of Clinical Oncology (2017)

5583 Background: Elevated Glioma-associated Oncogene Homolog-1 (Gli1) protein expression is associated with Hedgehog (Hh) pathway activation in high-grade serous ovarian cancer (HGSOC). Inhibition of Hh signaling in Gli1-overexpressing HGSOC patient-derived xenograft (PDX) inhibited tumour growth, particularly in combination with chemotherapy. Early phase HGSOC clinical trials of vismodegib, a potent Hh inhibitor (SMO inhibitor), were disappointing. We identified a HGSOC PDX harboring both Indian Hh ligand-overexpression and bi-allelic deletion of TSC1, which latter event is reported to derepress the mTOR pathway, driving non-cannonical Gli1 expression. We explored the effect of vismodegib in combination with cisplatin or the mTOR inhibitor, everolimus, in this model. Methods: A cell-line was generated from the well-characterised PDX (identity confirmed by PDX-specific p53 mutation). In vitro response to vismodegib was assessed. qRT-PCR was performed to establish Hh-ligand and Gli1 expression with/without SMO inhibition. A PDX was generated from this cell-line and randomized to in vivo treatment with cisplatin, vismodegib, everolimus or vehicle alone, or vismodegib in combination with cisplatin or everolimus. Results: The HGSOC cell-line was sensitive to vismodegib in vitro (EC50 of 3.5µM) and qRT-PCR analysis revealed down-regulation of Hh-ligand and Gli1 expression following in vitro SMO inhibition, confirming on-target vismodegib activity. In vivo treatment with vismodegib or everolimus alone did not result in reproducible in vivo efficacy. The combination of vismodegib + everolimus caused short-lived responses in 3 of 6 mice. Strikingly, in vivo treatment with vismodegib in combination with cisplatin impaired median survival (19 days) when compared with cisplatin treatment alone (43 days; p = 0.039) due to rapid tumour progression. Conclusions: Combining chemotherapy with Hh inhibition in Hh ligand-overexpressing HGSOC PDX with mTOR pathway activation may be detrimental. These findings highlight the importance of an in-depth understanding of tumour biology in order to effectively combine therapeutic approaches.
Clinical Management of Autoimmune Hepatitis in the Real World
Authors: R. Liberal, Y. de Boer, R.J. Andrade, G. Bouma, G.N. Dalekos, A. Floreani, D. Gleeson, G. Hirschfield, P. Invernizzi, M. Lenzi, A. Lohse, G. Macedo, P. Milkiewicz, B. Terziroli, B. van Hoek, J. Vierling, M.A. Heneghan
Journal: Journal of Hepatology (2016)
Adjuvant apatinib in nasopharyngeal carcinoma patients with residual Epstein-Barr virus DNA after curative radiotherapy: A phase IIa/IIb trial.
Authors: Jun Ma, Xu Liu, Guo Ling, Fangyun Xie, Weihan Hu, Rui Sun, Ying Sun, Mingyuan Chen
Journal: Journal of Clinical Oncology (2018)

e18063 Background: Nasopharyngeal carcinoma (NPC) is notable for its high incidence in select geographic and ethnic populations, including Southern China, Southeast Asia, North Africa, the Middle East and Alaska. Epstein-Barr virus (EBV) plays an important role in the development of NPC. Many studies have confirmed that residual EBV DNA after curative radiotherapy is a robust predictor of disease failure in NPC. Moreover, phase II trials have shown that anti-angiogenesis agents had promising antitumor activity in NPC. In this study, we aimed to investigate the efficacy and safety of apatinib, a vascular endothelial growth factor receptors 2 (VEGFR-2) inhibitor, as adjuvant therapy in NPC patients with residual EBV DNA after radiotherapy. Methods: Eligible patients will have newly diagnosed, non-metastatic NPC, with detectable plasma EBV DNA ( > 0 copy/ml) at the end of (+/- 1 week) radiotherapy or chemo-radiotherapy. This study includes two parts (IIa and IIb), the IIa part is a single arm study to evaluate safety and efficacy with target accrual of 25 patients. An analysis is planned after finish of phase IIa. The IIb part is a randomized, double-blinded, placebo controlled study, patients will be randomized to receive apatinib or placebo in a ratio of 1:1. The sample size of phase IIb will be determined based on the observed outcome in phase IIa. Aptinib (500mg) will be given orally every day continuously, 28 days as a cycle. The primary endpoint is disease free survival (DFS), and second endpoints include overall survival (OS), quality of life (QoL), and adverse events. To the best of our knowledge, this is the first trial to evaluate adjuvant target therapy in this subgroup of NPC patients with high risk of disease failure. Clinical trial information: NCT02874651. Results: not applicable Conclusions: not applicable Clinical trial information: NCT02874651.
Survey of implementation of antiemetic prescription standards in Indian oncology practices and adherence to ASCO's antiemetic clinical guideline.
Authors: Vijay Maruti Patil, Amit Joshi, Vanita Noronha, Shripad Dinanath Banavali, Purvish M. Parikh, Sunny Jandyal, Anant Ramaswamy, Kumar Prabhash
Journal: Journal of Clinical Oncology (2016)

e18230 Background: Adherence to ASCO antiemetic prophylaxis guidelines results in better control of chemotherapy induced nausea and vomiting. The level of implementation of these guidelines in India is unknown. This survey was planned to study the extent of implementation of “Antiemetics: ASCO clinical practice guideline (2011)” in routine adult solid tumor chemotherapy practice in India. Methods: This was an anonymized ethics committee approved cross sectional survey . The survey items were generated from the clinical questions given in the guideline. The survey was disseminated through personal contacts at the Indian biennial oncology conference and via e-mails to various oncology centers across India . A facility was considered to have fully implemented the ASCO guideline if it got an implementation score exceeding 90% in the B (B1, B2 & B3 combined) domain, partially implemented if the score was between 50-90% and not implemented if the score was below 50%. The B1, B2 and B3 domains included questions regarding the optimal antiemetic prophylactics for high, moderate and low-minimal emetogenic regimens. Descriptive statistics with 95% CI are provided. Results: 66 out of 105 centers responded (62.9%) with 65 centers (98.5%) were aware about presence of these guidelines .The partial , fully and no implementation status was 92.5% (95% CI 83.0-97.0%), 4.5% (95% CI 1.1-13.2%) and 3.0% (95% CI 0.3-11.2%) respectively. The prescription standards of antiemetics in highly emetogenic regimens were implemented fully by the least number of centers (6.1%), while those in low/minimal emetogenic regimen/ agents were implemented fully by the highest number of centers (34.8%). The most important factor hampering the implementation of ASCO guidelines was lack of sensitization (26, 39.4%). The data regarding differences in the pattern of implementation of standards according to location, funding source and type of institution (academic or private practice) will be presented at the meeting. Conclusions: Awareness regarding ASCO guidelines was very satisfactory but there is a need for sensitization of oncologists towards complete implementation of the same.
Sequential HLA‐haploidentical transplantation utilizing post‐transplantation cyclophosphamide for GvHD prophylaxis in high‐risk and relapsed/refractory AML/MDS
Authors: Alessia Fraccaroli, Dusan Prevalsek, Susanne Fritsch, Sarah Haebe, Veit Bücklein, Christoph Schulz, Max Hubmann, Hans‐Joachim Stemmler, Georg Ledderose, Andreas Hausmann, Christoph Schmid, Johanna Tischer
Journal: American Journal of Hematology (2018)

This study evaluates the role of sequential therapy in HLA-haploidentical transplantation (haplo-HSCT) of high-risk, relapsed/refractory AML/MDS. We analyzed the course of 33 adults with active disease at time of transplantation (AML n = 30; MDS n = 3; median age 58 years, range: 32-71). Sequential therapy consisted of cytoreductive chemotherapy (FLAMSA n = 21; clofarabine n = 12) applied shortly prior to reduced intensity conditioning for T-cell-replete haplo-HSCT using post-transplantation cyclophosphamide as GvHD prophylaxis. No graft rejection was observed. Complete remission at day +30 was achieved in 97% of patients. CI of acute GvHD grade II-IV and chronic GvHD was 24% (no grade IV) and 23%, respectively. NRM at 1 and 3 years was 15%, each. Severe regimen-related toxicities (grade III-IV) were observed in 58%, predominantly involving the gastrointestinal tract (diarrhea 48%, mucositis 15%, transient elevation of transaminases 18%). Probability of relapse at 1 and 3 years was 28% and 35%. At a median follow-up of 36 months, the estimated 1- and 3-year overall survival was 56% and 48%. Disease-free survival was 49% and 40%, respectively. At 3 years, GvHD and relapse-free survival (GRFS) was 24% while chronic GvHD and relapse-free survival (CRFS) was 29%. Thus, our results indicate that sequential haplo-HSCT is an effective salvage treatment providing high anti-leukemic activity, favorable tolerance, and acceptable toxicity in patients suffering from advanced AML/MDS.