tbuckley/cabot-search huggingface dataset:
Evaluation of a mobile application to prepare and engage cancer patients prior to a palliative care (PC) visit: Results of a randomized, controlled trial.
Authors: Arif Kamal, Fred Friedman, Jonathan Nicolla, Debra M. Davis
Journal: Journal of Clinical Oncology (2018)

10103 Background: Despite the growth in guidelines and evidence supporting routine PC for patients with advanced cancer, up to 40% of patients referred and given an appointment never show up. This high “no show” rate stems from patients harboring misconceptions about PC (e.g. confusing with hospice care) and not knowing its value. No tool to educate patients on the value of PC and prepare them for an upcoming visit has been tested. Methods: We conducted a randomized, controlled trial of PCforMe, a web-based mobile education and engagement tool, from December 2016 through February 2018. Patients were randomly assigned prior to a new PC clinic appointment to either PCforMe or an active control on a tablet device. The active control included three popular websites about PC developed by major specialty societies. We collected demographics and assessed system usability scores, patient preparedness (PEPPI), change in knowledge about PC, and change in no-show rate. Results: 78 patients were enrolled. Mean age was 61 (range 20-83) with 56% with less than a Bachelors education. The mean usability score was 77, putting PCforMe usability in the 90th percentile of mobile health tools. Scores on the single-item “I know what questions to ask” improved significantly (p < 0.002) after using PCforMe. Similar improvements were not seen in the control arms. Scores on the knowledge survey improved more in the intervention arm (p < 0.05). No show rates for new visits during the course of the trial decreased by 35%. Conclusions: Even among an elderly population with advanced cancer, a novel, mobile tool to prepare and engage cancer patients prior to a PC appointment is highly usable. The tool led to greater sense of readiness and familiarity with PC and reductions in the no-show rate to palliative care clinic. Larger, multi-site trials are needed to further test this novel tool.
Phase 2 study of neoadjuvant dabrafenib + trametinib (D+T) for resectable stage iiib/c BRAF-V600 mutation positive melanoma.
Authors: Robyn Saw, Alexander M. Menzies, Alexander Guminski, Omgo E Nieweg, Kerwin F. Shannon, Maria Gonzalez, Sydney Ch'ng, Richard Kefford, John F Thompson, Jonathan Stretch, Andrew J Spillane, Richard A Scolyer, Georgina V. Long
Journal: Journal of Clinical Oncology (2016)

9583 Background: Combination D+T improves the overall survival (OS) of patients (pts) with V600 BRAF-mutation positive advanced melanoma. D+T is currently being explored in an adjuvant study of pts with resected stage III melanoma (NCT01682083). We sought to explore neoadjuvant D+T for pts with bulky but resectable stage III melanoma (NCT01972347). Methods: In this phase 2 study, all pts received D (150 mg twice daily) + T (2 mg once daily) for 12 wks prior to complete resection of the pre-therapy tumour bed (RES), then 40 wks of further D+T. Eligible pts were ≥ 18 yrs, ECOG PS ≤ 1 with histologically confirmed resectable bulky stage IIIB/C BRAF V600E/K mutant melanoma. CT and PET scans were performed at baseline and 12 wks just prior to RES for RECIST and metabolic complete response (rCR and mCR respectively). CT monitoring was continued 12 wkly thereafter to 2 yrs then 6 mnthly to 3 yrs. Biopsies were taken at baseline and wk 1. The primary endpoints were the complete pathological response (pCR) and RECIST response rate (rRR) at wk 12. Secondary endpoints were surgical morbidity, mCR, relapse free survival (RFS), OS, toxicity and translational endpoints. Results: At data cut 4 Jan 2016, 19 had commenced D+T. 14 had reached RES (10 stage IIIC [2 in-transit only], 4 IIIB; 12 V600E, 1 V00K, 1 V600). At RES, 6/14 (43%) had pCR, 5/14 (36%) had rCR (rRR 93%), and 7/14 (50%) had mCR. All 6 pts with pCR had mCR, but 2 did not have rCR. No pt progressed during neoadjuvant treatment. 2/14 pts recurred in the resected field 12 and 36 wks after RES on D+T. These pts had the highest ctDNA at baseline. 8/14 (57%) had ≥ 1 surgical complication post RES; 8 had a wound infection requiring antibiotics, 5 had a seroma, 2 bled (1 wound evacuation). 11/14 had a post RES drain (median drain time 27d). 12/14 (86%) interrupted D+T in the first 12 wks for a median of 7d, 9 due to pyrexia ( ≥ 38.5oC). 1 pt ceased D+T at wk 28 due to renal failure. Conclusions: A high rate of pCR was observed with neoadjuvant D+T for resectable stage III melanoma. pCR correlated with mCR, but not rCR. Surgical complication rates were consistent with historic controls and stage of disease. The trial and translational research is ongoing, and ease of resection, RFS and OS data are being collected. Clinical trial information: NCT01972347.
Inhibition of MALT1 protease with biperiden or mepazine: A new therapeutic treatment approach in pancreatic cancer.
Authors: Alexander T. El Gammal, Leonie Konczalla, Nadine Scholz, Clarissa Klemp, Johanna Lueddeke, Annika Wolski, Yao Dichao, Gerrit Wolters-Eisfeld, Baukloh Julia, Bianca T. Hofmann, Sarah L Spriesterbach, Katharina Grupp, Christian Betzel, Svetlana Kapis, Theresa S Nuguid, Jakob R. Izbicki, Cenap Guengoer, Daniel R. Perez
Journal: Journal of Clinical Oncology (2016)

e14075 Background: Mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1) is a key mediator of NF-kB signaling and crucial for proliferation and anti-apoptosis in B-cell lymphomas. Mepazine (MEP) is a phenothiazine derivative and a potent MALT1 inhibitor. Biperiden (BIP) is a competitive receptor substrate of Phenotiazines. There is little data on the role of MALT1 in pancreatic ductal adenocarcinomas (PDAC). Methods: MALT1 expression was analyzed by IHC in 310 patients with PDAC. In silico docking was performed to determine favorable orientations and binding energies of MEP and BIP to the allosteric MALT1 binding pocket. Protein and mRNA expression of MALT1 were analyzed by Western blots and qRT-PCR. Five human PDAC cell lines were treated with different dosages of MEP and BIP. Proliferation rates were assessed by MTT and Ki67 assays. Apoptosis was determined by cleaved caspase 3 assays. MALT1 paracaspase activity assay was performed upon treatment with MEP or BIP. The effect of MEP and BIP on tumor size was evaluated by axenograft mouse model. A neurologic scoring was performed to asses adverse effects. Results: MALT1 is present in the majority of PDAC and absent in normal exocrine pancreatic tissue. BIP and MEP feature the same chemical structure activity relationship to the allosteric MALT1 binding-pocket. MALT1 is highly active in PDAC cells and can be inhibited by BIP or MEP leading to a significant reduction of proliferation and induction of apoptosis. Diminishing MALT1 activity prevents nuclear c-Rel translocation. PDAC tumor progression was significantly inhibited by BIP or MEP in vivo. Only mild neurologic adverse effects were determined. Conclusions: MEP and BIP are efficient inhibitors of MALT1 activity and PDAC tumor growth in vitro and in vivo. BIP or MEP treatment might be a promising new approach in pancreatic cancer therapy.
Depression and survival of glioma patients: A systematic review and meta-analysis.
Authors: Nayan Lamba, Chen Shi, Luo Zheng, David Cote, Quentin Regestein, Chunming Liu, Q Tran, Sugiti Routh, Timothy Smith, Rania Mekary, Marike Broekman
Journal: Journal of Clinical Oncology (2018)

2025 Background: There is currently a lack of well-established meta-analyses examining the association between depression and patient survival in glioma patients. The aim of this meta-analysis was to study the effect of depression on glioma patients' survival. Methods: A meta-analysis was conducted according to the PRISMA guidelines. PubMed, Embase, and Cochrane databases were searched for studies that reported depression and survival among glioma patients through 11/06/2016. Both random-effects (RE) and fixed-effect (FE) models were used to compare survival outcomes in glioma patients with and without depression. Results: Out of 619 identified articles, six were selected for the meta-analysis. Using RE model, the various measures of survival outcomes displayed worsened outcomes for both high and low grade glioma patients with depression compared to those without depression, with an overall pooled risk ratio for survival of 0.67 (95%CI: 0.46, 0.99; I2 = 51.4%, P-heterogeneity = 0.06); an overall pooled standard mean difference for the overall survival time (in months) of -0.88 (95%CI: -1.89, 0.13; I2 = 87.1%, P-heterogeneity < 0.01); and a pooled hazard ratio of death of 1.42 (95% CI: 1.00, 2.01; I2 = 0%, P-heterogeneity = 0.85). Using the FE model, results were similar except for overall survival time, where the shorter survival time in glioma patients with versus without depression reached statistical significance (-0.70; 95%CI: -0.86, -0.53). Among high-grade glioma patients, preoperative depression diagnosis was associated with fewer months of survival compared to postoperative diagnosis, as shown under the FE model (P-interaction < 0.01), but not under the RE model (P-interaction = 0.14). Conclusions: Among patients with either low or high-grade glioma, depression was associated with significantly worsened survival regardless of time of diagnosis.
The role of race and economic characteristics in the presentation and survival of patients with surgically-resected non-small cell lung cancer.
Authors: Kerri McKie, John M. Varlotto, Rick Voland, John Charles Flickinger, Malcolm M. DeCamp, Debra Maddox, Paul Rava, Thomas J. Fitzgerald, William Vincent Walsh, James Edward Liebmann, Karl Uy, Paulo Oliveira, Negar Rassaei, Heather A. Wakelee, Manali I. Patel, Jianying Zhang, Suhail M. Ali, Chandra Prakash Belani, Jennifer Baima, Cameron Stock
Journal: Journal of Clinical Oncology (2017)

e20053 Background: To investigate the inter-relation between economic, marital, and known histopathologic/therapeutic prognostic factors in presentation and survival of surgically-resected lung cancer patients in nine different ethnic groups. Methods: A retrospective review of the SEER database was conducted through the years 2007-2012. Population differences were assessed via chi-square testing. Multivariable analyses(MVA) were used to detect overall survival(OS) differences in the total surgical population (TS, N = 35,689) and in an early-stage (T1-T2 &lt; 4cm N0) surgically-resectable population(ESR, N = 17,931). Results: In the TS population, as compared to Whites, Blacks and Hispanics were more likely to present with younger age, adenocarcinomas, less married partnerships, no insurance, fewer stage I tumors, and fewer nodes examined, but their surgical procedure types and OS/LCSS were the same. MVA demonstrated that lower OS was associated with males, single/divorced/widowed partnership, lower income(TS only), and Medicaid insurance. MVA also found that all ethnic groups had a similar (Hispanics, Blacks) or better OS compared to Whites. 90-day mortality and positive nodes were correlated with not having insurance and not being married, but not ethnicity. Conclusions: In TS and ESR groups, OS was not different in the two largest ethnic groups (Black, Hispanic) as compared to Whites, but was related to single/widowed/divorced status, Medicaid insurance, and income (TS group only). Nodal positivity was associated with patients who did not have a married partner or insurance suggesting that psycho-social variables may impact disease biology in addition to the known histopathologic and treatment variables in patients undergoing surgical resection of early-stage lung cancer.
Distinctive chromosomal instability (CIN) patterns and its prognostic value in pancreatic neuroendocrine tumors (pNET).
Authors: James C. Yao, Abhishek Garg, David Chen, Eric Van Cutsem, Jaume Capdevila, Wei He, Markus Riester, Michael Morrissey, Maurizio Voi, Paul F. Engstrom, Rodney F. Pommier
Journal: Journal of Clinical Oncology (2016)

e23284 Background: MEN1, DAXX and ATRX are frequently mutated in pNET. Their associations with chromosomal aberrations, disease progression, and efficacy of targeted therapy have not been established. We explored these biomarkers in patients from RADIANT-3, a randomized phase 3 trial of everolimus (EVE) vs placebo in advanced pNET (Yao JC et al, NEJM 2011). Methods: Mutations and copy number analysis was performed on 65 archival tumor samples (15% of the trial population) using next-generation sequencing. Cox PH modeling was used to assess the association between groups defined by CIN and clinical outcome. Results: MEN1, DAXX, and ATRX were mutated in 42, 28, and 11% of pNET, respectively. DAXX and ATRX mutations were mutually exclusive; while 60% of DAXX and no ATRX mutation co-exist with MEN1. Three distinct CIN patterns were identified based on 2 mutually exclusive sets of chromosome aberrations; group 1 with loss of heterozygosity (LOH) in 1st set of chromosomes; group 2 with copy-neutral LOH in 1st set and gains in 2nd set of chromosomes; and group 3 with no recurring gains or loss. MEN1/DAXX/ATRX mutations were associated with CIN in group 1 and 2 (P < 1.8 x 10-10; Table). Group 1 and 2 had better prognosis than group 3 (median overall survival, 62.6 vs 37.9 mo; HR 1.86; 95% CI 0.96-3.6). All patients derived similar PFS benefit from EVE over placebo (group 1/2: median PFS, 12.5 vs 5.4 mo; HR 0.45; 95% CI 0.21-1; group 3: median PFS, 10.8 vs 4.6 mo; HR 0.57; 95% CI 0.22-1.46), consistent to that observed in overall study population (median PFS, 11.0 vs 4.6 mo; HR 0.35; 95% CI 0.27-0.45, P< 0.001). Conclusions: pNET showed 3 distinct CIN groups, with two groups tightly associated with commonly mutated genes. These molecular subtypes may have different disease prognosis, but all benefited similarly from EVE. Results upon statistical validation in larger cohorts may have far-reaching clinical applications. Clinical trial information: NCT00510068.CIN Group N = 65 (n/%) % Samples with MEN1, DAXX or ATRX aberrations Copy number aberrations Chromosome: 1, 2, 3, 6, 8, 10, 11, 15, 16, 21, and 22 Chromosome: 4, 5, 7, 9, 12, 13, 14, 17, 18, 19, and 20 Group 1 (30/46) 97 LOH Wild- type Group 2 (5/8) 100 Copy- neutral LOH Gain Group 3 (30/46) 23 Mostly wild-type Mostly wild- type
Temporal associations between prognostic indicators and overall survival after breast cancer.
Authors: Jennifer Kay Plichta, Samantha Marie Thomas, Oluwadamilola Motunrayo Fayanju, Laura Horst Rosenberger, Tristen Sinae Park, Terry Hyslop, Rachel Adams Greenup, Eun-Sil Shelley Hwang
Journal: Journal of Clinical Oncology (2017)

e18144 Background: Breast oncologists have little guidance on predicting long term outcomes after interval survival. We aim to evaluate the association of overall survival (OS) with select factors at multiple time points. Methods: Women ages 18-80 with non-metastatic invasive breast cancer were identified from the NCDB (2004─2014). Using multivariate survival analysis, we estimated the association of OS with tumor and treatment factors for those with follow up surviving at least 2, 5, and 10y post-diagnosis. Results: 685598 women (median age 59) were identified; 573757 were alive with follow up at 2y, 254303 at 5y, and 18640 at 10y. The majority had early stage, hormone receptor (HR) +, invasive ductal carcinoma. 57% underwent lumpectomy; 49% received chemotherapy; 89% of lumpectomies received radiation (RT); and 83% of HR+ tumors received endocrine therapy (ET). Of those alive at 2y, improved OS was associated with ER+, PR+, chemotherapy, RT, and ET. Reduced OS was associated with higher cT/cN stage, grade, and mastectomy. Of those alive at 5y, improved OS was associated with chemotherapy, RT, and ET. Reduced OS was associated with higher cT/cN stage, grade, and mastectomy. Of those alive at 10y, reduced OS was associated with higher cT stage and grade. Conclusions: Tumor and treatment factors are associated with OS, but the association of some factors may change for women surviving at least 5y or 10y. These findings may contribute to more tailored prognostication for patients based on interval survival. [Table: see text]
Reply to Jeffrey Graham, Omar Abdel-Rahman, Toni K. Choueiri, and Daniel Y.C. Heng's Letter to the Editor re: Fabio Conforti, Laura Pala, Vincenzo Bagnardi, et al. Cancer Immunotherapy Efficacy and Patients’ Sex: A Systematic Review and Meta-analysis. Lancet Oncol 2018;19:737–46
Authors: Fabio Conforti, Laura Pala, Vincenzo Bagnardi, Tommaso De Pas, Marco Martinetti, Giuseppe Viale, Richard Gelber, Aron Goldhirsch
Journal: European Urology (2018)
Second malignant neoplasms in a nationwide population-based cohort of childhood cancer survivors in Taiwan.
Authors: Chu-Ling Yu, Emily S. Tonorezos, Chiung-Yu Huang, Brian C-H Chiu, Chun-Ju Chiang, Hui-Ju Ch'ang, Yen-Lin Liu, James S. Miser, Hung-Yi Chiou, Yun Yen
Journal: Journal of Clinical Oncology (2017)

10569 Background: Childhood cancer survivors have excess risk of second malignant neoplasms, but data are limited in Asian populations. We established a nationwide retrospective cohort of childhood cancer survivors in Taiwan to study the risk of second malignant neoplasms in the population. Methods: Children and adolescents diagnosed with cancer before age 21 years between 1990 and 2011 were identified from the Taiwan Cancer Registry, the national cancer registry in Taiwan. One-year survivors of childhood cancer were ascertained through data linkage with the national death registry. Survivors were followed up through December 2012. Standardized incidence ratios (SIRs), absolute excess risks (AERs), and cumulative incidence of second malignant neoplasms were calculated. Results: A total of 186 second malignant neoplasms occurred among 15,263 1-year survivors of childhood cancer after a mean follow-up time of 8.0 years (SIR = 5.4, 95% confidence interval [CI] = 4.6-6.2; AER = 12.4 per 10,000 person-years). The most common types of second malignant neoplasms were gastrointestinal cancers (n = 37), leukemia (n = 28), endocrine cancers (n = 18), and brain cancer (n = 17). Cancers in the liver (n = 11, including 9 hepatocellular carcinoma) and colorectum (n = 16) accounted for 73% of second gastrointestinal malignant neoplasms in this population. The cumulative incidence of second malignant neoplasms at 10 and 20 years from follow-up was 1.0% (95% CI = 0.8-1.2%) and 3.0% (95% CI = 2.3-3.6%), respectively. Conclusions: Childhood cancer survivors in Taiwan experience excess risk of second malignant neoplasms, in particular gastrointestinal cancers, compared with the general population.
Complex association between social support and chemotherapy-related toxicities in older cancer patients.
Authors: Armin Shahrokni, Canlan Sun, William P. Tew, Supriya Gupta Mohile, Cynthia Owusu, Heidi D. Klepin, Cary Philip Gross, Stuart M. Lichtman, Ajeet Gajra, Vani Katheria, Harvey Jay Cohen, Arti Hurria
Journal: Journal of Clinical Oncology (2016)

10036 Background: Our study aims to evaluate the relationship between social support (SS) and chemotherapy-related toxicities (CRT) among older cancer patients. We hypothesized that patients with poor social support (PSS) would be at increased risk of CRT. Methods: This is a secondary data analysis on a previously reported study (Hurria et al, JCO 2011) that prospectively followed older (age 65+) cancer patients to assess the development of CRT, and its relationship with geriatric assessment items. A predictive model for CRT was developed (Cancer and Aging Research Group [CARG] CRT risk score). In this analysis, we assessed the relationship between patients’ SS (measured by Medical-Outcome Study-Social Support Survey-12 item), each item in social support survey, and the development of grade III or more hematological (H) and non-hematological toxicities (NH). Patients were categorized to PSS with total SS score of ≤ 75 and good social support (GSS) with a score of 76-100. Logistic and multinomial logistic regression was used to examine the association univariately as well as after adjusting for CRT risk score. Results: 498 older cancer patients were included for this study. Among these patients, 26% (n = 130) had PSS. After adjusting for the CARG CRT risk score, patients with PSS, had less documented grade III+ CRT compared to patients with GSS (OR = 0.58, P = 0.02). Assessing each individual SS item showed one item mostly accounted for this observation: whether the patient has someone to take them to the doctor. Patients who don’t have somebody to take them to doctors “most” or “all of the time”, were less likely to have grade 3+ CRT (OR = 0.43, p = 0.008) compared to patients who had someone to take them to doctors most or all of the time. This association strengthened after adjusting for CARG model (OR = 0.28, p = 0.001). The associations are similar for H (OR = 0.22, p = 0.005) and NH toxicities (OR = 0.33, p = 0.02). Conclusions: Contrary to our hypothesis, older cancer patients with PSS were less likely to develop CRT. However, less availability of having someone to take them to the doctor accounted for most of this finding. The possibility of significant underreporting by these patients needs to be explored in future studies.
Phase II study of alternate sunitinib schedule in patients with metastatic renal cell carinoma.
Authors: Eric Jonasch, Rebecca Slack, Daniel M. Geynisman, Matthew I. Milowsky, Kimryn Rathmell, Summer Stovall, Donna Juarez, Elizabeth R. Plimack, Nizar M. Tannir, Brian I. Rini
Journal: Journal of Clinical Oncology (2017)

4513 Background: Sunitinib is an antiangiogenic agent indicated for the treatment of metastatic renal cell carcinoma (mRCC). Sunitinib is given in a 4 week on, 2 week off (4/2) schedule. Significant toxicities are observed in patients in the 3 rd and 4 th weeks of therapy. We hypothesized that a 2 week on, 1 week off (2/1) schedule would provide improved toxicity without compromising efficacy. Methods: A multicenter, single arm study was performed, with patients initiating sunitinib 50mg on a 2/1 schedule. Schedule and dose alterations were performed if grade &gt; 3 toxicities were observed. The primary objective was to determine the percentage of patients who experienced grade &gt; 3 fatigue, diarrhea, or HFS. The sample size of 60 patients was selected to ensure the upper bound of a 95% confidence would fall below standard schedule rate of 25%-30% if sample rate was 10%-15%, respectively. Secondary outcomes included response rate (RR), progression free survival (PFS) and dose reductions. Results: Between August 2014 and April 2016, 60 patients were enrolled, and 59 treated. Patients had a median age of 65.5 years (ranging from 45-92). 24% of patients (14/59) had grade 3 or higher fatigue, diarrhea, or HFS (95% CI: 13.6%, 36.6%). This is similar to the average of the 4 week on, 2 week off schedule of 25%-30%, and the lower bound of the confidence interval is in the center of our target rate of 10%-15%. Among events at least possibly related to study drug, patients were most likely to experience the expected events of diarrhea (75% with 5 grade 3 events), fatigue (71% with 6 grade 3 events), and HFS (54% with 3 grade 3 events). 22 (37%) patients responded (25.0%, 50.9%). Among patients with secondary endpoint data available, median PFS was 19.3 months (95% CI: 8.2, NR) and 33/56 (59%) of patients underwent dose reduction. Conclusions: Sunitinib administered in a 2/1 schedule in this study did not result in a lower rate of grade 3 or higher fatigue, diarrhea or HFS when compared to historical data from trials employing a 4/2 schedule. However, efficacy data showed robust response rate and a prolonged PFS, suggestive of long-term tolerability in patients receiving sunitinib on a 2/1 schedule. Evaluation of toxicity kinetics and patient quality of life is ongoing. Clinical trial information: NCT02060370.