tbuckley/cabot-search huggingface dataset:
Attitudes of oncology physicians and nurses toward euthanasia and death with dignity.
Authors: Hui-ping Chen, Xin-mei Luo, Boyan Huang, Di Luo, Bo Zheng, Yu Jiang
Journal: Journal of Clinical Oncology (2016)

e21502 Background: In mainland China, euthanasia and death with dignity (DWD, which is equivalent to natural death in USA), don’t have clear legal provisions, so oncology physicians and nurses fall in a dilemma when facing the request of DWD or euthanasia from cancer patients. In order to investigate the understanding and attitude of oncology medical staff towards euthanasia and DWD, we designed this study. Methods: A questionnaire investigating the understanding and attitudes towards DWD or euthanasia was administered to oncology physicians and nurses of 11 hospitals in mainland China. Results: A total of 570 questionnaires were collected, including 228 clinicians and 342 nurses. There were 99.6% doctors and 96.5% nurses known euthanasia, otherwise only 79% of doctors and 70.5% of nurses known DWD. Only 77.9% participants know the distinction between DWD and euthanasia; about 9.8% participants believed that DWD was euthanasia. There were 68.4% physicians and 47.7% nurses once received patients’ DWD request. The most important reason was “unwilling to survive through machines”. Meanwhile, 52.6% physicians and 37.7% nurses received euthanasia request. The main reason was “suffering from intractable pain symptoms”. More physicians (88.6%) and nurses (86.0%) supported the DWD legalization than euthanasia legalization. The physicians who had higher education degree more opposed the legalization of euthanasia. More physicians (73.7%) and nurses (67.5%) were willing to implement DWD for terminal cancer patients than euthanasia at present. If the legalization of DWD and euthanasia, the percentage of physicians and nurses who were willing to implement DWD (84%,70.5%) and euthanasia(66.2%,60.5%) would increase (P < 0.001), but there were still more doctors and nurses prefer to implement DWD for terminal cancer patients than euthanasia (P < 0.001). Conclusions: The understanding of DWD is far less than euthanasia among oncology physicians and nurses, even one fifth medical staff confused them. However, most of them more support DWD than euthanasia, especially after legalization. The legalization and standardization of DWD are more in line with the principles of medical ethics than euthanasia and worth considering in mainland China.
Sequential administration of high-dose interleukin-2 and ipilimumab in patients with metastatic melanoma.
Authors: Sapna Pradyuman Patel, Denai Milton, Mohammed M. Milhem, Lawrence E. Flaherty, Sigrun Hallmeyer, Lynn G. Feun, Ralph J. Hauke, Lee D. Cranmer, Gregory A. Daniels, Gary C. Doolittle, Bret Taback, Michael Morse, Jose Lutzky, William Howard Sharfman
Journal: Journal of Clinical Oncology (2016)

e21041 Background: Immunotherapy with high dose IL-2 (HD-IL2) has been shown to induce long-term durable responses in a subset of patients (pts) with metastatic melanoma (MM). Combination immunotherapy, involving concomitant or sequential administration, may enhance the fraction of pts with long-term control. IL-2, an immune activating cytokine, and ipilimumab (IPI), a CTLA-4 immune checkpoint inhibitor, offer complementary mechanisms relating to efficacy in mm pts. We initiated a Phase IV open-label study to assess sequenced use of HD IL-2 and IPI in pts with MM. Methods: Between September 2013 and May 2015, twenty nine pts with Stage IV mm were randomized to receive treatment with 2 courses of HD IL-2 (600,000 IU/kg) followed by induction IPI 3 mg/kg for four doses, or vice-versa. The primary objective of the study was to compare 1-year OS with that of historical control (Hodi et al, NEJM 2010). The Evaluable Population (EP) was defined as pts who received at least 50% of planned treatment with each study drug. Results: 13 pts were randomized to receive HD IL-2 first, and 16 were randomized to receive IPI first. 20 pts were included in the EP: 7 in the HD IL-2 first arm, 13 in the IPI first arm. For the EP, 1-year OS was 77%, 1-year PFS was 26%, and the overall response rate (ORR) was 25%. The frequency of adverse events (AEs) was similar in both treatment arms. Of the 28 pts in the Safety Population, 12 reported occurrence of Grade 3 or higher AEs, including 3 who ended study as a result. There was one treatment-related death in a patient receiving cycle 1 of HD IL-2 who developed cerebral hemorrhage as a result of thrombocytopenia. Conclusions: HD IL-2 and IPI may be administered sequentially in pts with MM, with an acceptable toxicity profile that is consistent with known AEs for each agent. The primary efficacy endpoint of 1-year OS (77%) in this small sample size was superior to that of IPI alone (46%) from historical studies. The ORR of the combination appears to be higher than the additive anticipated response rate of each monotherapy. These data provide preliminary evidence for synergistic effects of coordinated administration of these two agents. Clinical trial information: NCT01856023.
Evaluation of the significance of TERT mutations in the presence of NF1 mutations in high grade glioma.
Authors: Evangelia Razis, Vassiliki Kotoula, Georgia-Angeliki Koliou, Eleni Vrettou, Eleni Giannoulatou, Ioannis Sotirios Tikas, Stefanos V. Labropoulos, Kyriaki Papadopoulou, Georgios Rigakos, Styliani Papaemmanoyil, Ourania Romanidou, Panagiotis Nomikos, Georgios Iliadis, Panagiotis Selviaridis, Konstantinos Polyzoidis, George Fountzilas
Journal: Journal of Clinical Oncology (2018)

e14058 Background: We have shown the significance of NF1 mutations(mut) in a group of high grade gliomas, and their association with IDH mut. The significance of TERT has also been shown. However, the role of TERT in the setting of NF1 mut is not known. Methods: A total of 101 patients with grade III-IV gliomas treated with standard of care were included in the analysis. While 55 genes were tested by NGS, mut were found in 37 and where included in the analysis. TERT was tested with Sanger sequencing. Results: The median age was 54.7 years, most patients were males (57.4%) and most had undergone a subtotal tumor resection (59.4%). 85 patients were diagnosed with grade IV gliomas, while 16 had grade III tumors. TERT, TP53, IDH, EGFR, PTEN and NF1 were the most frequently mutated genes. 72 tumors carried TERT mut, 24 had wild-type(WT) TERT, while for 5 patients the status of TERT was unknown. TP53 and IDH mut were found in 24.8% and 13.9% of the tumors, respectively, while 14.9% carried EGFR mut. 23 patients had WT TERT and NF1, 66 had WT NF1 and mutated TERT, 6 patients had mut in both genes and in one tumor TERT was WT and NF1 was mutated. Mutated TERT was more frequently observed in patients with WT IDH and TP53 (p = 0.019 and p = 0.006, respectively), while WT TP53 was associated with WT IDH (p < 0.001). With a median follow-up of 82.3 months (mos), 87 patients have died. The median overall survival (OS) is 22 mos (95% CI 17.3-27.9), while the 12-mo OS rate is 74.3%. Among patients with WT TERT and NF1, the median OS was 40.82 (95% CI 28.10-94.10), while among patients with WT NF1 and mutated TERT it was 18.46 (95% CI 14.89-22.00). Patients with mutated NF1 and TERT experienced worse OS than those without (HR = 3.19, 95% CI 1.44-7.06, p = 0.004 and HR = 2.26, 95% CI 1.33-3.84, p = 0.003, respectively), while patients with mut in IDH were at lower risk of death (HR = 0.24, 95% CI 0.11-0.52, p < 0.001). Upon multivariate analysis, TERT did not retain its unfavorable prognostic significance for OS either when adjusting for age and NF1 mutational status (p = 0.13) or in the model adjusting for age and IDH mutational status (p = 0.21). Conclusions: TERT seems to lose its importance in the face of NF1. IDH with NF1 may suffice to identify three groups with distinct prognosis.
P04.23 Pericytes contribute to tumour immune system evasion in glioblastoma multiforme through the under-expression of ICAM-1, VCAM-1 and MCP-1.
Authors: M O Joret, T I Park, J M Macapagal, J Rustenhoven, B J Kim, J Correia, E Mee, R L M Faull, P Schweder, M Dragunow
Journal: Neuro-Oncology (2018)

Glioblastoma multiforme (GBM) is the most common and fatal type of primary malignant brain cancer in adults. Tumour micro-environment immunosuppression is a hallmark of the disease and largely contributes to its recalcitrance to conventional cancer therapies. Current research to better understand GBM-mediated immunosuppression has focused on glioma cells as well as tumour associated microglia and macrophages, leaving pericytes - perivascular cells with demonstrated immune functions - largely unstudied. In a field of research plagued by poor translational validity of animal models, we studied immunologically relevant differences in patient-matched GBM and normal brain pericytes, focusing on proteins involved in immune system activation. Patient-matched GBM pericytes and normal brain pericytes were isolated and cultured from surgically excised samples donated by consenting patients undergoing tumour resections at Auckland City Hospital. Following treatments with differential concentrations of pro-inflammatory cytokines, we studied the expression and secretion of adhesion molecules ICAM-1 and VCAM-1 and chemoattractant molecule MCP-1 through a variety of molecular studies. Our research reveals that patient and passage matched GBM and normal brain pericytes have different immune phenotypes. Specifically, GBM pericytes have an immunosuppressive propensity characterized by a curbed expression and secretion of ICAM-1, VCAM-1 and MCP-1 in response to the common pro-inflammatory trigger IL-1β. Our study is the first to characterise differences in the immune profiles of patient-matched normal and GBM primary human brain pericytes. Our results support the involvement of human pericytes in GBM tumour immune escape. A better understanding of tumour micro-environment immunosuppression in GBM would present immense potential in the development of new immunotherapeutic agents.
Neuromodulation of lumbosacral spinal networks enables independent stepping after complete paraplegia
Authors: Megan L. Gill, Peter J. Grahn, Jonathan S. Calvert, Margaux B. Linde, Igor A. Lavrov, Jeffrey A. Strommen, Lisa A. Beck, Dimitry G. Sayenko, Meegan G. Van Straaten, Dina I. Drubach, Daniel D. Veith, Andrew R. Thoreson, Cesar Lopez, Yury P. Gerasimenko, V. Reggie Edgerton, Kendall H. Lee, Kristin D. Zhao
Journal: Nature Medicine (2018)
Safety and efficacy of apixaban and rivaroxaban in cancer-associated venous thromboembolism (CA-VTE): A community-based retrospective analysis.
Authors: Bibek Singh Pannu, Amani Erra, Taha Alrifai, Phyo Thazin Myint, Salman Syed
Journal: Journal of Clinical Oncology (2018)

e13577 Background: Cancer patients have an increased risk of developing VTE when compared to the general population. Moreover, these patient have a higher risk of recurrence of their VTE. Current guidelines recommend the use of Low Molecular Weight Heparin for the treatment of CA-VTE. However, there has been emerging data on the use of Direct-Acting Oral Anticoagulants (DOACs) in the treatment of CA-VTE. Methods: We performed a retrospective chart review of patients receiving Rivaroxaban (R) or Apixaban (A) at Connolly Cancer Center between 8/2014 - 8/2017. Patients diagnosed with acute VTE 3 months prior to cancer diagnosis or with concurrent active cancer, were included in the study. Measured outcomes were: all cause mortality, major bleeding (as defined by International Society of Thrombosis and Hemostasis), minor bleeding, recurrent VTE and anticoagulant substitution. Fisher exact test and Odds Ratio (OR) were used for statistical analysis. Results: 78 patients with active cancer, who were receiving either R (n = 64) or A (n = 14) were identified. Mean age was 63.4 and 71.7 in the R and A groups, respectively, with equal gender distribution. In each group, more than 64% of patients were on anticoagulation for at least 6 months. No difference was found in the safety or efficacy outcomes between the R and A groups (major bleeding 7.8% and 7.1%; minor bleeding 9.4% and 7.14%; total recurrent VTE 9.4% and 21.4%, respectively). Females had a higher bleeding risk (major and minor) when compared to males, irrespective of anticoagulant type, with an odds ratio of 6.03 [95% CI = 1.2384-29.3844]. All-cause mortality was similar between the two groups (35.9% and 42.9% for the R and A groups, respectively). Anticoagulant substitution was more frequently observed in the A group (28.6%) than in the R group (3.1%) (p = 0.0084). Conclusions: We found no difference in safety or efficacy outcomes of R versus A in CA-VTE. A higher rate of bleeding was observed among female patients. Patients on A were more likely to require switching to a different anticoagulant. This study warrants larger head-to-head studies comparing different DOACs, in patients with CA-VTE.
A proposed measurement scheme when lymph nodes split on serial CT in clinical trials.
Authors: Ahmad Shafiei, Mohammadhadi Bagheri, Faraz Farhadi, Nathan Lay, Jianhua Yao, Les R. Folio, Elizabeth C. Jones, Ronald M. Summers
Journal: Journal of Clinical Oncology (2018)

e18591 Background: To compare measurement strategies of lymph node sizes which split into fragments over time when using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Methods: We retrospectively identified target lymph nodes that split (Split Nodes) from previously conglomerated nodal mass from 182 patients with different cancers. We measured target lymph nodes (≥ 1.5 cm) at baseline and follow-up CT scans of chest, abdomen, and pelvis in PACS. The sum of short axis diameters of all Split Nodes fragments was recorded as the RECIST 1.1 measurement. Our lesion response method uses the short axis measurement of the largest fragment (Largest Fragment) of the Split Nodes. To get an estimate of response rate, short axis of three non-splitting well-circumscribed lymph nodes were recorded as Surrogate nodes. Mean percentage change of the Surrogate nodes was considered as the ground truth. RECIST calculations were compared with the Surrogate and Largest Fragment measurements. T-test was used for statistical analysis. Results: Twenty Split Nodes were identified. While in all cases the Surrogate Lesions indicated a decrease in size, RECIST showed an increase in size in 45% of the cases. The mean reduction of RECIST size was -6%. Mean size change using Largest Fragment was -52% which was close to ground truth of Surrogate Lesions (-46%). (Table 1) There was a significant difference (P < 0.001) between mean percent change in the size of Surrogate lesions and RECIST, whereas no significant difference (P = 0.26) was found between mean percent change in Surrogate lesions and our proposed Largest Fragment method. Conclusions: Measuring short axis diameter of the Largest Fragment is more reliable than RECIST 1.1 for measuring Split Nodes and can improve RECIST tumor measurement in clinical trials. Table 1. Percent size change by RECIST 1.1, Surrogate Lesion and Largest Fragment in 20 Split Nodes % Size Change Mean Min Max RECIST 1.1 -6 -48 +44 Surrogate Lesions -46 -70 -10 Largest Fragment -52 -81 -28
First-line afatinib (A) vs gefitinib (G) for patients (pts) with EGFR mutation positive (EGFRm+) NSCLC (LUX-Lung 7): Patient-reported outcomes (PROs) and impact of dose modifications on efficacy and adverse events (AEs).
Authors: Vera Hirsh, James Chih-Hsin Yang, Eng-Huat Tan, Ken O'Byrne, Li Zhang, Michael J. Boyer, Tony Mok, Ki Hyeong Lee, Shun Lu, Yuankai Shi, Sang-We Kim, Janessa J. Laskin, Dong-Wan Kim, Catherine Dubos Arvis, Karl Kölbeck, Martin H. Schuler, Dan Massey, Angela Maerten, Luis Paz-Ares, Keunchil Park
Journal: Journal of Clinical Oncology (2016)

9046 Background: The phase IIb LUX-Lung 7 (LL7) trial compared the 2nd-generation ErbB family blocker, A 40 mg/day, and the 1st-generation reversible EGFR TKI, G 250 mg/day in pts with treatment (tx) naïve EGFRm+ NSCLC. The co-primary endpoints, PFS and TTF were significantly better with A vs G, as was ORR. To explore pt experience of tx we report PROs (secondary endpoint) and post-hoc analysis of the impact of dose adjustment of A on PFS and AEs. Methods: PROs were assessed using EQ-5D utility and EQ-VAS scores. To optimize individual tolerability, the dose of A could be reduced by 10 mg decrements to a minimum of 20 mg in the event of grade ≥ 3 (or selected grade 2) drug-related (DR) AEs. PFS was compared between pts who had a dose reduction within 6 mos and those who received ≥ 40mg for the first 6 mos. Incidence/severity of common AEs before/after dose reduction from 40 mg was assessed. Results: There was no significant/clinically meaningful difference in mean EQ-5D (baseline to post-baseline, A: 0.72 to 0.77; G: 0.73 to 0.80; p = 0.142) or EQ-VAS (A: 69.7 to 74.5; G: 71.2 to 76.0; p = 0.20) with A and G. Of 160 pts treated with A (40 mg), 63 (39%) had a dose reduction to 30 mg; 21 (13%) had a further dose reduction to 20 mg. Dose reductions were more frequent in non-Asians than Asians (64 vs 36%). There was no significant difference in PFS in pts who received < 40 mg or ≥40 mg (median: 12.8 vs 11.0 mos; HR [95% CI]: 1.3 [0.9–2.0]; p = 0.14). Dose reduction of A reduced the incidence/severity of DR AEs (Table), and did not diminish its effects on PROs (EQ-5D, < 40 mg: 0.69 to 0.74, ≥ 40 mg: 0.73 to 0.77; EQ-VAS, < 40 mg: 72.4 to 70.5, ≥40 mg: 68.6 to 75.4). Conclusions: Improvements in PROs were similar in pts treated with A or G. As with LL3/LL6 dose adjustment of A in LL7 reduced the frequency/intensity of DR AEs without compromising efficacy. This enables pts to remain on effective tx without affecting PROs. Clinical trial information: NCT01466660.AE, %* Pre-dose reduction (n = 63) Post-dose reduction (n = 63) All Grade ≥ 3 All Grade ≥ 3 Diarrhea 95.2 25.4 61.9 9.5 Rash/acne 81.0 20.6 52.4 3.2 Stomatitis 60.3 7.9 33.3 0 *In pts requiring dose reduction of A (63/160 pts); rate of grade ≥ 3 diarrhea in all pts: 12.5%
Clinical utility of the revised international staging system (RISS) in newly diagnosed multiple myeloma.
Authors: Nidhi Tandon, S.Vincent Rajkumar, Martha Lacy, Angela Dispenzieri, Francis Buadi, Morie A. Gertz, Suzanne R. Hayman, Nelson Leung, Ronald S. Go, David Dingli, Prashant Kapoor, Yi Lin, Yi Lisa Hwa, Amie Fonder, Miriam Hobbs, Steven R. Zeldenrust, John Anthony Lust, Wilson I. Gonsalves, Stephen Russell, Shaji Kumar
Journal: Journal of Clinical Oncology (2016)

8017 Background: A recent pooled analysis of 11 international trials formulated a new prognostic algorithm called the Revised International Staging System (RISS) for Newly Diagnosed Multiple Myeloma (NDMM) patients. It combined the International Staging System (ISS) with high risk chromosomal abnormalities (CA) [del 17p, t (4; 14), t (14; 16)] detected by interphase fluorescent in situ hybridization (FISH) and serum lactate dehydrogenase (LDH) levels. However, it has been derived from data obtained from patients enrolled in clinical trials only. We examined its utility in an unselected cohort of patients with NDMM. Methods: Clinical and laboratory data of 1900 patients with NDMM seen at Mayo Clinic within 90 days of their diagnosis, between January 2005 and December 2015, was collected by chart review and analyzed retrospectively to calculate the RISS score. The primary end point of overall survival (OS) was defined as the time from diagnosis until death from any cause. Log rank test was used to estimate difference in the survival curves. Results: The median age was 64.5 yrs (22-95) and 59.85% were males. Median estimated follow up for the entire cohort was 4.4 yrs (95% CI; 4.1, 4.6). Among the 1900 patients, high risk CA by FISH was present in 15.6%, absent in 57.4% and data was missing in remaining 28%. LDH was elevated in 14.1%, normal in 66.1% and missing in 19.8%. ISS could be calculated in 1633 (85.9%) patients; of whom 481(29.4%) were in ISS I, 651(39.9%) in ISS II and 501(30.7%) in ISS III. Out of the 1350(71%) patients in whom RISS could be calculated, 229(17%) were RISS I, 936(69.3%) were RISS II and 185(13.7%) were RISS III. The median OS for the entire cohort was 5.9 yrs (95% CI; 5.5, 6.4). Conclusions: The RISS combines the prognostic power of high risk CA and LDH with ISS score and gives a better differentiation of MM patients into 3 survival subgroups. It should be used to stratify patients in future clinical trials to guide towards more effective personalized treatment. RISS ISS (N=1633) RISS (N=1350) I II III I II III N 481 (29%) 651 (40%) 501 (31%) 229 (17%) 936 (69%) 185 (14%) Median OS yrs 8.6 (7, NR) 6.1 (5.6, 7.1) 3.7 (3.1, 4.2) 10 (7.2, NR) 6 (5.5, 7.7) 2.5 (2.2, 3.1) 5 yr OS % 72% 59% 40% 76% 58% 30%
Clinical effect of liver transaminase abnormalities after ablation of ovarian cancer.
Authors: Kelly J Manahan, John P. Geisler
Journal: Journal of Clinical Oncology (2017)

e17042 Background: At initial presentation, patients with ovarian cancer often have disease involving the upper abdomen and specifically the liver (surface or parenchyma). The object of this study was to 1) see the difference in liver enzyme levels in women getting tumor ablation involving the liver compared to women getting tumor ablation not involving the liver and to 2) see if any differences had a readily noticeable clinical effect. Methods: A series of twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction with tumor ablation involving the liver were compared to twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction and tumor ablation without involvement of the liver. The data were compared with Fisher’s exact, Chi-square or Mann-Whitney U as appropriate. Results: Women undergoing tumor ablation involving the liver compared with women undergoing tumor ablation not involving the liver had significantly elevated AST and ALT levels the first day after surgery (p = 0.002; 0.002, respectively). There were no significant differences in age, operative blood loss or need for transfusion (p=0.24; 0.065; 0.33, respectively). The mean time for resolution of the elevations of AST and ALT was 2.5 days (95% CI = 1.8-3.2) for AST and 2.8 days (95% CI = 2.0 -3.6) for ALT. Conclusions:Significant elevations in AST and ALT occur when tumor involving the liver is ablated in women undergoing debulking for ovarian cancer. This elevation does not appear to increase operative blood loss or need for transfusion.