tbuckley/cabot-search huggingface dataset:
Impact of comorbidity and age on survival among older veterans with early stage non-small cell lung cancer (NSCLC).
Authors: Melisa L. Wong, Sunny Wang, Ying Shi, Curtis J Wozniak, Louise C Walter
Journal: Journal of Clinical Oncology (2014)

7540 Background: Older age has been shown to be a stronger predictor of treatment receipt than comorbidity for NSCLC of all stages. We hypothesized that comorbidity would be a stronger predictor of survival than age among veterans with early stage NSCLC. Methods: We obtained first-line treatment and overall survival to 5 years from the Veterans Affairs Central Cancer Registry for 6,361 veterans age ≥ 65 diagnosed with stage I-II NSCLC from 2003-2008. Veterans were grouped by age (65-74, ≥ 75), Charlson comorbidity index (CCI 0, 1-3, ≥ 4), and stratified by first-line treatment. Log-rank tests and Cox proportional hazards models were used to identify differences in 5-year survival according to comorbidity and age. Results: Median age at diagnosis was 74 and median CCI was 2 (range 0-13). 2,840 (45%) patients received surgery: 2,219 lobectomies (includes 135 pneumonectomies) and 621 sublobar resections. 1,645 (26%) patients received radiation and 1,876 (29%) received other/no treatment. When stratified by age and comorbidity, veterans with CCI 0 who underwent surgery had similar 5-year survival regardless of age and veterans with CCI ≥ 4 had the worst 5-year survival across all treatment groups. In the lobectomy group, 5-year survival for veterans with CCI 0 was 64% for age 65-74 and 59% for age ≥ 75; for veterans with CCI ≥ 4, 5-year survival was 49% for age 65-74 and 50% for age ≥ 75 (log-rank test, p = .002). In multivariable analysis, severe comorbidity was one of the strongest predictors of 5-year survival for all treatment groups along with stage and geographic region. The hazard ratio for 5-year mortality for CCI ≥ 4 was 1.45 (95% CI 1.16-1.83) in the lobectomy group and 1.75 (95% CI 1.11-2.75) in the sublobar resection group. Age had only a modest effect on mortality in the lobectomy group (HR 1.16; 95% CI 1.01-1.34) and radiation group (HR 1.15; 95% CI 1.01-1.31) but was not prognostic in the other treatment groups. Conclusions: Severe comorbidity is a much stronger predictor of overall survival than age in early stage NSCLC. Therefore, elderly patients with minimal comorbidity should be considered for surgical evaluation.
Molecular profiling of clear cell ovarian carcinoma.
Authors: Michael Friedlander, Kenneth Russell, Sherri Z. Millis, Zoran Gatalica, Andreas Voss
Journal: Journal of Clinical Oncology (2014)

5516 Background: Clear cell ovarian carcinomas (CCOCs) are a distinct histopathological subtype and account for 5-10% of epithelial ovarian cancers (EOCs). They have a poor prognosis in advanced stages and at recurrence. They are commonly resistant to platinum-based chemotherapy and treatment options are limited in patients with progressive disease. Molecular profiling may identify patient subsets who could benefit from targeted therapies when standard treatment has failed and also provide an insight into the genomic heterogeneity of CCOC’s that share a similar phenotype. Methods: Over 435 CCOC’s referred to Caris Life Sciences (from 2009 - 2014) were evaluated; diagnoses were based on reported pathology. Specific testing was performed per physician request and included a combination of sequencing (Sanger, NGS or pyrosequencing), protein expression (IHC), gene amplification (CISH or FISH), and/or RNA fragment analysis. Results: Patients were further grouped into pure CCOCs (n=363) and mixed CCOCs (n=72). The most common findings in CCOC’s were overexpression of TOP2A (61%), TS (52%), TLE3 (48%), loss of TUBB3 (49%) and MGMT (56%). cMET was overexpressed in 19% of CCOCs tested and in 6% of mixed CCOCs. CCOCs had lower expression of AR, ER, and PR (7%, 9%, and 15%) than mixed CCOCs (21%, 39%, and 31%) and EOCs (24%, 45%, and 30%). In 69 CCOC’s analyzed by NGS, PIK3CA was the most common mutation (52% - vs. 8% in all EOCs and 14% in mixed CCOCs) followed by TP53 (16%) and KRAS (11%). Mutations in FBXW7 (10%), APC (7%) and ATM (6%) were observed at a higher rate than in all EOCs. No BRAF mutations were seen. In the 33 CCOCs with PIK3CA mutations, 4 (12%) had co-existing mutations in KRAS and 2 (6%) had TP53 mutations while 70% (23/33) overexpressed cMET and 12% had a loss of PTEN. Conclusions: Molecular profiling of proteins, gene expression, and mutations underscores the heterogeneity of CCOC and the potential role in better selecting patients for clinical trials. Drugs, which target the mTOR pathway or cMET may have therapeutic potential in selected subsets. Mutations in FBXW7, APC and ATM may also help direct patients to trials of targeted therapies.
ALS-implicated protein TDP-43 sustains levels of STMN2, a mediator of motor neuron growth and repair
Authors: Joseph R. Klim, Luis A. Williams, Francesco Limone, Irune Guerra San Juan, Brandi N. Davis-Dusenbery, Daniel A. Mordes, Aaron Burberry, Michael J. Steinbaugh, Kanchana K. Gamage, Rory Kirchner, Rob Moccia, Seth H. Cassel, Kuchuan Chen, Brian J. Wainger, Clifford J. Woolf, Kevin Eggan
Journal: Nature Neuroscience (2019)
A surgeon’s view of excising the “surgeon ego” to accelerate progress in the culture of surgery
Authors: Kevin J H Newman
Journal: BMJ (2019)

Myers and colleagues dwell on the tiny percentage of “super ego” driven surgeons who give the surgical dog such a bad name.1 I know of no other surgeons arrogant enough to have branded their patients.

Surgeons can be shy people, often in some degree of emotional turmoil after tragedy but adept at concealing it from colleagues.

Surgeons literally have …
Childhood cancer burden: a review of global estimates
Authors: Nickhill Bhakta, Lisa M Force, Claudia Allemani, Rifat Atun, Freddie Bray, Michel P Coleman, Eva Steliarova-Foucher, A Lindsay Frazier, Leslie L Robison, Carlos Rodriguez-Galindo, Christina Fitzmaurice
Journal: The Lancet Oncology (2019)
B‐cell phenotype and function in infants with egg allergy
Authors: Melanie R. Neeland, David J. Martino, Thanh D. Dang, Jennifer J. Koplin, Rachel L. Peters, Alexander Grishin, Shyamali C. Dharmage, Mimi L. Tang, Hugh A. Sampson, Richard Saffery, Katrina J. Allen
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Correction: Outcomes after endoscopic resection of large laterally spreading lesions of the papilla and conventional ampullary adenomas are equivalent (Endoscopy (2018) 50 DOI: 10.1055/a-0587-5228)
Authors: Amir Klein, Zhengyan Qi, Farzan F. Bahin, Halim Awadie, Dhruv Nayyar, Michael Ma, Rogier P. Voermans, Stephen J. Williams, Eric Lee, Michael J. Bourke
Journal: Endoscopy (2018)

In the above-mentioned article, the arrangement of Fig. 1 has been corrected. This was corrected in the online version on September 10, 2018.
Mucormycosis Among Children with Hematological Malignancies Is Associated with High-Risk Acute Lymphoblastic Leukemia and Is Often Salvageable
Authors: Sarah Elitzur, Shlomit Barzilai, Assaf Arie Barg, Bella Bielorai, Ronit Elhasid, Salvador Fischer, Yariv Fruchtman, Gil Gilad, Shai Izraeli, Mira Kharit, Ruth Laor, Itzhak Levy, Ronit Nirel, Dror Raviv, Yael Shachor-Meyouhas, Isaac Yaniv, Nira Arad-Cohen
Journal: Blood (2018)
Demonstrating preclinical efficacy of AUY922, a novel Hsp90 inhibitor, alone and in combination with standard chemotherapy or radiation in esophageal adenocarcinoma.
Authors: Juliann Kosovec, Christina Rotoloni, Ali H Zaidi, Yoshihiro Komastu, Lori Kelly, Daisuke Matsui, Amina Waheed, Toshitaka Hoppo, Blair A Jobe
Journal: Journal of Clinical Oncology (2014)

e13506 Background: Several novel target agents, including heat shock protein 90 (Hsp90) inhibitor, AUY922, are being explored as treatment options for esophageal adenocarcinoma (EAC). Hsp90 is a chaperone protein, involved in cell signaling and proliferation. Client proteins of Hsp90 are known to stabilize cancer cell growth by supporting proliferation. The current study demonstrates the in vitro and in vivo efficacy of AUY922 in EAC. Methods: Baseline expression of Hsp90 was established in human and rat EAC versus normal samples. OE19 and OE33 cell lines and a modified Levrat model in Sprague-Dawley rats (n=16) were used to evaluate the effects of AUY922. In vitro, WST-1, BrdU ELISA and flow cytometry were used to determine the effective dose (ED50), assess proliferation and measure apoptosis, respectively. In vivo, tumor growth was evaluated by baseline and post-treatment MRIs. A subset of rats received pre-treatment endoscopies with biopsy collection. Pathway inhibition was evaluated, in vitro and in vivo, by RT-PCR of Hsp90α, Hsp70, Hsp72, CDK1 and CDK4. Efficacy of AUY922 in combination was determined in vitro by BrdU of radiated cells or cells treated with cisplatin and 5-fluorouracil (5-FU). Results: The ED50 of AUY922 was established at 30ηM in vitro, and 50mg/kg in vivo. Human and rat samples showed that Hsp90 was upregulated in EAC tissue compared to normal. Decreased proliferation was seen in vitro post AUY922 versus untreated. Likewise, in vivo model demonstrated stable tumor size in 76.9%, a decrease in 15.4% and an increase in 7.7%. Gene expression in vitro and in vivo exhibited a decrease in Hsp90α, CDK1 and CDK4 and an increase in Hsp72 expression. Anti-proliferative effects of radiation or cisplatin and 5-FU were significantly enhanced by addition of AUY922. Conclusions: AUY922 inhibited Hsp90 pathway expression, resulting in decreased proliferation in vitro and stable disease in vivo, with the greatest effect seen in combination with radiation or cisplatin and 5-FU. This provides a strong rationale for clinical evaluation of AUY922 in single or combination setting for human EAC.
Spiritual wellbeing’s clinical utility in quality-of-life assessment.
Authors: Ian N. Olver, Hayley Suzanne Whitford
Journal: Journal of Clinical Oncology (2014)

e20552 Background: The biopsychosocialspiritual model attests that spiritual wellbeing improves quality of life (QOL) assessment accuracy and provides clinical utility; however our attempts to replicate initial findings of clinical significance are complex. Methods: Part of a larger Australian online longitudinal survey, 883 female cancer survivors (M = 56 years old) completed the Depression Anxiety Stress Scale (DASS21); the Functional Assessment of Cancer Therapy – General (FACT-G) to assess QOL; and the Functional Assessment of Chronic Illness Therapy – Spiritual Wellbeing - Expanded (FACIT-Sp-Ex) to assess underlying spiritual domains of Peace, Meaning, Faith, and the under-researched Relational factor. Results: Survivors enjoying life to the fullest at baseline (n = 435) reported high Peace despite suffering fatigue (Φ = .46), nausea, (Φ = .41) both p < .001, and pain (Φ = .11, p = .05). This support for our previous findings was again only evident for the high Peace/high symptom group with high life enjoyment not mirrored in other group combinations. The same pattern was shown for participants enjoying life who reported high Meaning despite pain (Φ = .28), fatigue (Φ = .25), and nausea (Φ = .35), all p < .001. Results were not significant for Faith and Relational domains. Findings were supported by low reports of psychological distress (moderate-to-extremely severe Depression 13.7% and Anxiety 15.0%) compared to normative ranges of 24-45%, alongside high levels of symptoms like pain (93.0%) and fatigue (95.2%) compared to norms (fatigue 49%; pain 26%). Thus expectedly, Peace showed large-to-moderate correlations with Depression (r = -.65) and Anxiety (r = -.40), as did Meaning (Depression r = -.69, Anxiety r = -.34), all p < .001. Conclusions: Patients and survivors with cancer suffering chronic physical symptoms appear to make the most of their lives, experiencing elevated peace and meaning, lending support to Park and Folkman's (1997) model of meaning in the context of stress and coping. Meaning gains growing attention in the literature yet peace is a neglected construct warranting much attention especially as a highly clinically significant influence in quality of life in oncology.
Reviving the Clinician Scientist: A Best Practice Model
Authors: Nelly Monzer, Wolfgang Herzog, Bernd Löwe, Stephan Zipfel, Peter Henningsen, Matthias Rose, Marco Lehmann, Katrin Elisabeth Giel, Birgitt Marten-Mittag, Felix Fischer, Mechthild Hartmann
Journal: Psychotherapy and Psychosomatics (2019)
VOLTAGE: Multicenter phase 1b/II study of nivolumab monotherapy and subsequent radical surgery after preoperative chemoradiotherapy with capecitabine in patients with locally advanced rectal cancer.
Authors: Yuichiro Tsukada, Hideaki Bando, Koji Inamori, Shota Fukuoka, Takeshi Sasaki, Yuji Nishizawa, Daisuke Kotani, Motohiro Kojima, Yosuke Togashi, Naoki Nakamura, Tetsuo Akimoto, Yoshito Komatsu, Satoshi Yuki, Shigenori Homma, Yutaka Hatanaka, Yoshihiro Matsuno, Akihiro Sato, Hiroyoshi Nishikawa, Masaaki Ito, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2018)

TPS878 Background: Fluoropyrimidine-based chemoradiotherapy (CRT) and subsequent radical surgery (SRS) are widely accepted as standard treatment for patients (pts) with locally advanced rectal cancer (LARC). Pathological complete remission (pCR) rates are associated with improved clinical outcomes. An important target, high-frequency microsatellite instability (MSI-H), was identified for which anti-PD-1 antibodies confirmed robust antitumor activity in metastatic colorectal cancer (mCRC). Recently, improved therapeutic effects by combining an immune checkpoint inhibitor with radiotherapy (RT) have been reported in pts with other cancer types. Furthermore, sequential use of an anti-PD-1 antibody after RT has demonstrated synergistic effects in in vivo models. The purpose of this study is to investigate safety, efficacy, and proof-of-concept (POC) of nivolumab (Nivo) monotherapy plus SRS after pre-CRT in non-MSI-H and MSI-H pts with LARC. Methods: The inclusion criteria are: LARC in the lower/middle rectum; clinical stage, T3–4 N-any M0; age ≥20 years; and 50.4 Gy of concurrent pre-CRT completed with daily 1,650 mg/m 2 of capecitabine. Within 2 weeks after pre-CRT, 240 mg of Nivo is administered every 2 weeks 5 times before SRS, which is performed at least 2 weeks after Nivo treatment. The purpose of P1b is to evaluate dose-limiting toxicity and determine the recommended P2 dose (RP2D). In P2, the efficacy and safety of Nivo at RP2D are evaluated. The primary endpoint is the pCR rate by independent central assessment in pts with non-MSI-H LARC. Secondary endpoints include disease-free and overall survival and adverse events. Fifty pts including 40 non-MSI-H and 10 MSI-H pts will be enrolled. As an exploratory biomarker study, repeated biopsies from primary sites and blood collections will be performed 4 times during the treatment courses (before and after pre-CRT, during Nivo treatment, and at SRS), and phenotypes of immune-competent cells, neoantigens, T cell receptor repertoire, and enteric bacteria will be evaluated. As of September 2017, P1b has been completed and P2 is ongoing. Clinical trial information: NCT02948348.
Mice Expressing MYC and NrasQ61R in Germinal Center B Cells Develop Highly Aggressive Multiple Myeloma
Authors: Adhithi Rajagopalan, Zhi Wen, Quinlan Furumo, Erik A. Ranheim, Remington Finn, Evan Flietner, Grant Yun, Yun Zhou, Mei Yu, Natalie Scott Callander, Marta Chesi, P. Leif Bergsagel, Robert Burns, Demin Wang, Fotios Asimakopoulos, Jing Zhang
Journal: Blood (2018)
Generation of a Half-Life Extended Anti-CD19 BiTE® Antibody Construct Compatible with Once-Weekly Dosing for Treatment of CD19-Positive Malignancies
Authors: Grit Lorenczewski, Matthias Friedrich, Roman Kischel, Christoph Dahlhoff, Jonas Anlahr, Mercedesz Balazs, Dan Rock, Michael C Boyle, Rebecca Goldstein, Angela Coxon, Tara Chapman-Arvedson
Journal: Blood (2017)
Dihydropyrimidine dehydrogenase gene (<i>DPYD</i>) polymorphisms associated with toxicity in patients treated with flourpyrimidines in northern Brazil.
Authors: Williams Fernandes Barra, Ney PC Santos, Danielle Costa, Samia Demachki, Paulo P Assumpção, Sidney Santos, Andrea KCR Santos, Mayara F Mota, Tayssa CL Vilhena, Millene A Bechara
Journal: Journal of Clinical Oncology (2014)

e13546 Background: DPD deficiency is associated with severe toxicity after 5-FU treatment. There are regional differences in tolerance to 5-FU. No data about toxicity to 5-FU in cancer patients in northern Brazil. No data evaluating polymorphisms in DPYD and toxicity to 5-FU in admixed populations. The aim was to evaluate the relation of two DPYD polymorphisms (*2 and *5) with toxicity in cancer patients treated with fluoropyrimidines in admixture population. Methods: A cross-sectional study was done, including cancer patients treated with fluoropyrimidines in 3 oncology center in Belem, northern Brazil. Clinical data were recovered from medical records. Analysis of polymorphisms has used TaqMan® system. 48 markers ancestry informative have been used as genomic control method. The Structure v.22 software was used to estimate the individual and overall proportion of ancestry. Results: 151 patients treated with fluoropyrimidines were included. The mean age was 55.3 years (range 18-86) and 52.7% of the sample were men. Colorectal cancer (44,7%) and gastric câncer (39,9%) were more common primary site. 5-FU alone was used in 45% of cases and the average number of cycles was 5.98 (range 1-24). The averages ancestries were 62.4% European, 25.2% Native American and 12.4% African. Among patients with available information, 80 (70.8 %) had some degree of toxicity (grade 1-4), while only 18 (15.9 %) had severe toxicity (grade 3 and 4). There was one death related to 5-FU toxicity. The homozygous for the polymorphism DPYD*5 was related to the 8-fold increase in the occurrence of severe toxicity (p=0.037). No DPYD*2 polymorphism was found. There was a significant correlation between the occurrence of any toxicity and African ancestry (p = 0.035). Although not statistically significant, the average African ancestry was higher in patients with severe toxicity (p = 0.185). The Native American ancestry showed a trend of protection against severe toxicity (p = 0.059). Conclusions: The data reinforce the importance of variations in the DPYD in fluoropyrimidines tolerance and suggest the control of ancestry as importante factor to personalize chemotherapy in admixed populations.
Impact of weekend admission on hospital length of stay and organ failure in pediatric leukemia patients at free-standing U.S. children’s hospitals.
Authors: Elizabeth Kimbell Goodman, Anne F. Reilly, Yimei Li, Alix Eden Seif, Julie Fitzgerald, Yuan-Shung Huang, Rochelle Bagatell, Brian Fisher, Richard Aplenc
Journal: Journal of Clinical Oncology (2014)

6598 Background: In adult leukemia patients, weekend admission is associated with increased inpatient mortality. We used a U.S. cohort of pediatric leukemia patients to evaluate the impact of weekend admission on clinical outcomes in index leukemia admission. Methods: The Pediatric Health Information System (PHIS) database was used to assemble a retrospective cohort of children with newly diagnosed ALL or AML identified from 43 freestanding children’s hospitals between January 1, 1999 to December 31, 2011. Index admissions were dichotomized as ‘weekend’ (Saturday or Sunday) and ‘weekday’. Admission mortality, length of stay, time to chemotherapy, and organ system failure were compared between weekday and weekend admissions. Bivariate analyses were performed using Chi-square and Student’s t tests. Adjusted analyses were performed using logistic regression. Results: 10,720 ALL patients and 1,323 AML patients were identified; 2,009 patients (16.7%) were admitted on weekends. Weekend admissions had a significantly higher proportion of young, non-white, and publically-insured patients. Patients receiving ICU-level resources within the first 2 days of admission represented a higher percentage of total weekend admissions although the absolute numbers of these severely ill patients was constant. Patients admitted on the weekend did not have an increased index admission mortality (OR 0.96, 95% CI 0.57-1.61 %); however, they had significantly increased length of stay (1.38 day increase, p<.001), time to chemotherapy (0.36 day increase, p<.001), and risk of respiratory failure (OR 1.47, 95% CI 1.16-1.71) after adjusting for demographics, severity of illness, and hospital level factors. Conclusions: While newly diagnosed children with leukemia admitted on weekends do not have higher index admission mortality, they have an increased length of stay, time to chemotherapy, and rate of respiratory failure. A higher proportion of patients are severely ill at presentation. Optimizing weekend resources may reduce hospital length of stay across all weekend admissions and ensure the availability of comprehensive care for those weekend admissions with higher acuity.
Consolidation therapy with the combination of bortezomib and lenalidomide (VR) without dexamethasone in multiple myeloma patients after transplant: Effects on survival and bone outcomes in the absence of bisphosphonates
Authors: Evangelos Terpos, Efstathios Kastritis, Ioannis Ntanasis‐Stathopoulos, Dimitrios Christoulas, Athanasios Papatheodorou, Evangelos Eleutherakis‐Papaiakovou, Nikolaos Kanellias, Despina Fotiou, Dimitrios C. Ziogas, Magdalini Migkou, Maria Roussou, Ioannis P. Trougakos, Maria Gavriatopoulou, Meletios A. Dimopoulos
Journal: American Journal of Hematology (2018)

Optimizing consolidation treatment in transplant-eligible newly diagnosed multiple myeloma patients in order to improve efficacy and bone-related outcomes is intriguing. We conducted an open-label, prospective study evaluating the efficacy and safety of bortezomib and lenalidomide (VR) consolidation after ASCT, in the absence of dexamethasone and bisphosphonates. Fifty-nine patients, who received bortezomib-based induction, were given 4 cycles of VR starting on day 100 post-ASCT. After ASCT, 58% of patients improved their response status, while following VR consolidation 39% further deepened their response; stringent complete response rates increased to 51% after VR from 24% post-ASCT. VR consolidation resulted in a significant reduction of soluble receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio and sclerostin circulating levels, which was more pronounced among patients achieving very good partial response or better. After a median follow-up of 62 months, no skeletal-related events (SREs) were observed, despite the lack of bisphosphonates administration. The median TTP after ASCT was 37 months, while median overall survival (OS) has not been reached yet; the probability of 4- and 5-year OS was 81% and 64%, respectively. In conclusion, VR consolidation is an effective, dexamethasone- and bisphosphonate-free approach, which offers long OS with improvements on bone metabolism and no SREs.