tbuckley/cabot-search huggingface dataset:
Insomnia symptoms and memory problems in adult survivors of childhood cancer: A report from the St. Jude Lifetime Cohort Study.
Authors: Tara M. Brinkman, Belinda Neal Mandrell, Chenghong Li, Zsila Sousan Sadighi, Deokumar Srivastava, Leslie L. Robison, Melissa M. Hudson, Kevin R. Krull
Journal: Journal of Clinical Oncology (2016)

10575 Background: Adult survivors of childhood cancer are at-risk of developing sleep and cognitive problems. No studies have examined the contribution of insomnia symptoms to cognitive function in this population. Methods: 642 adult survivors of pediatric cancer with mean[SD] current age = 34.5 years[9.2] and years since diagnosis = 25.9[9.1] completed standardized assessments of intelligence, memory, attention, and executive function. Age-adjusted z-scores were calculated using national normative data (M = 0, SD = 1). Insomnia symptoms were defined as difficulty falling asleep within 30 minutes and nighttime or early morning awakenings ( > 3 times per week). Functional impairment was defined as severe daytime fatigue or sleepiness. Multivariable regression models examined associations between sleep and cognition, adjusted for age, sex, age at diagnosis, and primary treatment exposures (cranial irradiation, methotrexate, anthracyclines, corticosteroids). Separate multivariable models were adjusted for emotional and physical late effects (psychological distress, pain, physical inactivity, obesity). Results: 133 (21%) of survivors reported symptoms of insomnia; 61 (10%) reported insomnia symptoms and daytime fatigue or sleepiness. In multivariable models adjusted for primary cancer therapies, insomnia symptoms were associated with worse performance on multiple measures of verbal memory and learning; the magnitude of associations, approximately one-half standard deviation, was greater in survivors with insomnia and functional impairment: short-term memory (β = -0.66, 95% CI, -0.94 to -0.38, P< 0.0001); long-term memory (β = -0.51, 95% CI, -0.80 to -0.22, P= 0.0003), verbal learning (β = -0.52, 95% CI, -0.80 to -0.23, P= 0.0003), vocabulary (β = -0.47, 95% CI, -0.73 to -0.21, P= 0.0006). Similar associations were observed in models adjusted for emotional and physical late effects. Conclusions: Survivors with symptoms of insomnia performed significantly worse on memory measures than survivors without such symptoms; observed risk exceeded that associated with cranial irradiation. Interventions targeting insomnia symptoms may confer cognitive benefit in survivors.
TCT-112 Patient-oriented clinical outcomes and net adverse cardiovascular event in the Global Leaders trial
Authors: Patrick Serruys, Ply Chichareon, Rodrigo Modolo, Norihiro Kogame, Kuniaki Takahashi, Chun-Chin Chang, Taku Asano, Yuki Katagiri, Mathias Vrolix, Krzysztof Zmudka, Carlo Tumscitz, Leonardo Bolognese, Ton Slagboom, Kurt Huber, Robert-Jan van Geuns, Pascal Vranckx, Marco Valgimigli, Stephan Windecker, Yoshinobu Onuma
Journal: Journal of the American College of Cardiology (2018)
The use of rituximab to manage B cell-mediated autoimmune thrombocytopenia (AITP) during concurrent program death ligand-1 (PD-L1) immunotherapy.
Authors: Michael Castro
Journal: Journal of Clinical Oncology (2016)

e14545 Background: For patients receiving PD-1/L1 inhibitors, about half develop some manifestation of autoimmunity, and 5-10% develop severe to life-threatening autoimmune problems. As a matter of convention, the discontinuation of immune checkpoint inhibitors was adopted during clinical development and made its way into the package inserts governing administration of these agents. However, for some patients, corticosteroids may dampen or eliminate the benefit of immunotherapy altogether. Methods: A patient with metastatic clear cell carcinoma of the ovary treated with nivolumab developed grade 4 AITP (PLTs 9,000/µL). During the initial nivolumab treatment, the absolute lymphocyte count was more than 2000/μL, but then fell precipitously during corticosteroid therapy to as low as 163/μL. Concomitantly, the CA125 rose indicating disease progression after corticosteroids were given. Hence, a steroid-sparing strategy utilizing rituximab (375 mg/m2/wk) was employed to avoid the lympholytic effects of corticosteroids. Results: Rituximab reversed the AITP, and corticosteroids were weaned. After the platelet count rose above 50,000/μL, nivolumab was restarted. The patient derived a second round of disease control after immunotherapy was resumed. There were no adverse effects observed from concurrent rituximab and nivolumab therapy. Conclusions: Corticosteroid administration can result in loss of disease control from immune checkpoint inhibitor therapy, presumably by ablating acquired tumor immunity. Rituximab appears to be a useful means of treating unwanted B cell autoimmunity and minimizing the use of corticosteroids and their adverse impact against tumor immunity. Besides AITP, other B cell-mediated autoimmune manifestations such as hepatitis, thyroiditis, arthritis, pancreatitis, and glomerulonephritis in principle would be reversible with this approach. The selective control of B cell mediated autoimmunity with rituximab appears to be a useful strategy for continuing immune checkpoint inhibitor therapy after severe autoimmune toxicity.
Presence and percentage of type 2 papillary RCC in mixed (type 1 and type 2) papillary renal cell carcinoma does not portend worse prognosis in patients treated by partial/radical nephrectomy in non-metastatic disease.
Authors: Andrew Leone, Gregory Diorio, Joseph Brito, Kamran Zargar, Gyan Pareek, Joseph F. Renzulli, Shohreh I Dickinson, Ali Amin, Wade Jeffers Sexton, Philippe E. Spiess, Michael Adam Poch, Dragan Golijanin
Journal: Journal of Clinical Oncology (2016)

e16126 Background: Subclassificaiton of papillary RCC (pRCC) into type 1 and type 2 has been recognized as an independent negative prognostic factor. Little investigation has determined the effect of percentage of types 1 and 2 tumors and the impact on patient survival and prognosis. Methods: We reviewed 106 patients from 2005-2015 at two institutions who underwent partial (PN)/radical nephrectomy for M0 pRCC. Upon pathological re-review by two GU pathologists, pRCC cases were divided into three cohorts: those with pure type 1 pRCC (N = 23; 22%), pure type 2 (n = 14; 13%) and those with mixed type 1 and type 2 pRCC (N = 69, 65%) and demographic/clinical information was compared using student's t test and Fisher's exact test and overall comparison using MANOVA test with cox regression multivariate model and Kaplan Meir curves for disease free survival. Results: Comparisons between the three cohorts (pure type 1, pure type 2, mixed types 1 & 2) surgery type (PN more likely in pure type 1), nuclear grade, presence of necrosis (78%, 43%, 51%) and pathological T stage were different (p = 0.041, < 0.001, 0.49) and tumor size approached significance with average tumor size of 1.6, 4.9, 3.4 cm. (p = 0.078). Age, gender, pathological N stage, and median follow up were similar On multivariate cox regression for disease free survival, there was no statistical difference in the three cohorts based on type 1, type 2 or mixed (3,3,8 deaths/metastases/recurrence). Pathological T stage was independently associated with DFS (p = 0.019). Conclusions: Disease free survival (DFS) rates in patients with mixed type 1 and type 2 compared to pure type 1 and type 2 pRCC were not statistically different. Presence of necrosis was more likely in pure type 1 pRCC. Patients with pure type 2 pRCC had higher pathological T stage compared to mixed patients. Pathological T stage was independently associated with disease free survival on multivariate analysis. Further research including larger multi-institutional studies with longer follow up is needed to determine if routine pathological subclassificaiton of type 1 and type 2 pRCC correlates with outcome.
Loss-of-function of PBRM1 to predict response to anti-PD-1/PD-L1 therapy in metastatic renal cell carcinoma.
Authors: Diana Miao, Claire Margolis, Dylan Martini, Stephanie Anne Mullane, Dana Cullen, Christine Horak, Megan Wind-Rotolo, Matthew David Hellmann, Martin Henner Voss, Robert J. Motzer, Craig Norton, Sabina Signoretti, Alexandra Snyder Charen, Eliezer Mendel Van Allen, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2017)

3016 Background: Immune checkpoint inhibitors targeting programmed cell death-1 (PD-1) substantially improve patient survival in clear-cell renal cell carcinoma (ccRCC), but predictive biomarkers for efficacy have not yet been identified. Methods: We analyzed whole exome sequencing (WES) from a clinical trial of anti-PD-1 monotherapy (nivolumab) for ccRCC (N = 34) to discover genomic predictors of response to immune checkpoint therapy, and validated our findings in 28 ccRCC patients from 2 institutions treated with anti-PD-1 or anti-PD-L1 therapies. We defined 3 response groups: clinical benefit (CB) – complete or partial response by RECIST or stable disease with objective decrease in tumor burden and progression free survival (PFS) &gt; 6 months - and no clinical benefit (NCB) – progressive disease with PFS &lt; 3 months, with all other patients in intermediate benefit (IB). We further validated our findings in WES from 212 melanoma patients treated with immune checkpoint therapies in 3 published cohorts. Results: Biallelic loss of the chromatin remodeling subunit PBRM1, mutated in 34/62 (55%) patients across both cohorts and up to 41% of ccRCC overall, was the only gene mutation associated with CB in both the training (p = 0.0064; Pearson’s chi-squared) and validation cohorts (p = 0.043), and predicted both PFS and overall survival (OS) (p = 0.042 and 0.014, respectively; Kaplan-Meier). In 212 melanomas, truncating alterations in ARID2 – a closely related chromatin remodeler - were also enriched in responders after correcting for tumor mutational burden (p = 0.036), and having a truncating alteration in either PBRM1 or ARID2 significantly predicted overall survival (p = 0.022). In this ccRCC cohort, tumor mutational burden and loss of antigen presentation machinery were not associated with CB or NCB. Conclusions: Loss of chromatin remodeling subunits may impact response to immune checkpoint therapy in both ccRCC and melanoma. Further study in larger cohorts of immunotherapy-treated patients and functional characterization of ARID2 and PBRM1 in the context of the tumor-immune microenvironment will help to determine potential for further biomarker development.
A phase 1 trial extension to assess immunologic efficacy and safety of prime-boost vaccination with VXM01, an oral T cell vaccine against VEGF-receptor 2, in patients with advanced pancreatic cancer.
Authors: Friedrich Hubertus Schmitz-Winnenthal, Lilli Podola, Nicolas Hohmann, Tobias Friedrich, Heinz Lubenau, Marco Springer, Klaus M. Breiner, Gerd Mikus, Markus W. Büchler, Anne-Valerie Keller, Ruhan Koc, Christoph Springfeld, Phillip Knebel, Thomas Schmidt, Mariana Bucur, Lars Grenacher, Walter E. Haefeli, Philipp Beckhove
Journal: Journal of Clinical Oncology (2016)

3091 Background: VXM01 is an orally applied tumor vaccine based on live, attenuated salmonella bacteria carrying a eukaryotic expression plasmid, which encodes VEGFR-2. A recent randomized and placebo controlled phase I trial demonstrated in advanced pancreatic cancer patients safety, immunogenicity and T cell response related transient anti-angiogenic activity of 4 priming vaccinations applied within one week. As VEGFR2 specific T cell responses gradually declined after a peak response at day 21, an extension trial was conducted to explore whether monthly boost vaccinations can be safely administered and maintain increased vaccine specific T cell levels. Methods: 18 patients with advanced pancreatic cancer received a priming regimen with VXM01 followed by 6 monthly boost vaccinations starting on day 38 and 8 patients received placebo treatment in a randomized and blinded fashion. Immunomonitoring involved IFN-gamma Elispot analysis against VEGFR2 derived long peptides and was performed on blood samples harvested on days 0, 4, 14, 21 and 38 and 10 days after boost vaccination. Results: 12 out of 18 vaccinated patients showed considerable, in some cases high, increases in VEGFR2 specific T cell response over d0 levels. In the entire vaccinated group, VEGFR2 specific T cells peaked after 3 months with an average 4-fold increase over d0 levels. At study completion after 6 months VEGFR2 specific T cells were still increased over d0 values. Drug-related adverse events preferentially associated with boosting doses of VXM01 were decreases in lymphocyte count (22% vs 0) and increases in diarrhea (22% vs 0). Median overall survival was 9.3 months in the vaccinated group and 8.4 months in the placebo group. Within the vaccinated group, patients with a T-cell response to VXM01 showed a longer median overall survival (10.3 months) than patients without (5.4 months). Conclusions: Oral prime boost vaccination with VXM01 was well tolerated and is suitable to induce and maintain for several months effector T cell responses against VEGFR-2 in advanced stage pancreatic cancer patients. Clinical trial information: EudraCT 2011-000222-29.
Relationship of self-reported food insecurity and symptom burden in patients with cancer.
Authors: Emmaline Reed Longnecker, Christian A. Thomas, Tracey Weisberg
Journal: Journal of Clinical Oncology (2018)

e18771 Background: One in eight residents in Maine are food insecure, higher than the national average of one in six. NECS is partnered with a local food bank to help identify food insecure patients so they can receive services. The current study was aimed to understand how food insecurity affects patient reported outcomes (PRO) in a hematology/oncology practice. Purpose: To determine if food insecurity is associated with a change in symptom burden reported in PRO surveys. Methods: From 1.1-12.31.17 we identified 150 oncology/hematology patients who indicated food insecurity as part of their PRO survey, distributed prior to each patient visit. Food secure case control matches controlled for disease, stage, gender and age (n = 150) were identified for the same time period. The following PROs were assessed and graded based on CTCAE 4.0 guidelines: difficulty sleeping, fatigue, pain, mood and appetite. Results: Patients indicating food insecurity reported a higher symptom burden compared to case control matches (table 1). Using a correlated t-test, the differences in scores were found to be statistically significant with 99% power. Table 1: Averages denote the average of all symptom scores for all patients in 2017 in each category. Higher numbers denote a higher symptom burden. T-values were calculated using a correlated t-test. Confidence Intervals were calculated from t-values. P-values were converted from t-values for convenience of reading. Conclusions: Cancer patients with food insecurity self-report a significantly higher burden of symptoms compared to matched controls who are food secure. We hypothesize that improved access to social services could alleviate the symptom burden of cancer patients irrespective of disease related factors. PRO Symptom Food Insecure Average Food Secure Average T-Values * 99% Confidence Interval for the Difference P-Values ** Difficulty Sleeping 0.9806 0.5198 5.552 .6775, .2443 < .00001 Fatigue 1.382 0.7957 10.906 1.069, .6560 < .00001 Mood 1.109 0.4897 6.563 .8659, .3733 < .00001 Pain 1.092 0.5938 6.63 .6945, .3023 < .00001 Appetite 0.5627 0.2958 3.895 .4456, .0881 0.000074 *values > 2.352 are significant**values < .01 are significant
Identifying continuing educational needs among oncologists in managing patients with pancreatic cancer.
Authors: Wendy Cerenzia, Sharon Hwang, Khalid Kevin Mamlouk, Beloo Mirakhur, Benjamin Leon Musher
Journal: Journal of Clinical Oncology (2018)

e16233 Background: Most patients with pancreatic ductal adenocarcinoma (PDAC) are diagnosed with advanced disease and are ineligible for potentially curative surgical resection. Oncologists are faced with considering all treatment options, including experimental agents in clinical trials. The goal of this study was to identify the current practice of US-practicing medical oncologists in the management of patients with advanced PDAC in order to ascertain future continuing medical educational (CME) needs. Methods: Oncologist practice was assessed using a case-vignette survey with multiple-choice and Likert-type questions designed to elicit clinical management decisions, determine familiarity with new and emerging therapy, and assess challenges to managing patients with PDAC. The survey featured two vignettes: 1) a 55 year-old male with a pancreatic tail mass and numerous liver metastases 2) a 77 year-old male with a pancreatic head mass, biliary obstruction, and metastases to the liver and peritoneal cavity. Results: Responses were collected from 150 medical oncologists using a quota method; 69% practiced in a community setting and 31% were academicians. Results demonstrated a lack of consensus in management selections, notably when sequencing therapy. Further, few ( < 10%) recommended a clinical trial in either vignette. Academic oncologists reported a higher percentage of patients with stage IV PDAC enrolled in clinical trials compared to community oncologists (30% vs 14%, P < .001). However, 36% of all oncologists rated ‘lack of access to clinical trials’ as a significant barrier to patient care. Variation was also noted in familiarity with pathophysiology and knowledge of therapies to treat PDAC, with academic oncologists reporting significantly higher familiarity compared to community oncologists. Conclusions: By assessing the practice patterns of oncologists managing patients with advanced PDAC, this study identified variation in management decisions and demonstrated continuing educational needs. Future CME that is centered on identified educational needs will help oncologists continue to translate the latest evidence into practice and provide optimal care of patients with PDAC.
Disease-free survival in patients at highest risk of recurrent renal cell carcinoma in S-TRAC.
Authors: Alain Ravaud, Daniel J. George, Robert J. Motzer, Allan J. Pantuck, Michael D. Staehler, Lucile Serfass, Sriram Krishnaswami, Michelle Casey, Liza L DeAnnuntis, Mariajose Lechuga, Bernard Escudier
Journal: Journal of Clinical Oncology (2018)

4565 Background: Sunitinib (SU) is FDA-approved for adjuvant treatment of patients (pts) at high risk (≥T3, any Fuhrman grade and/or nodal involvement [N+]) of recurrent renal cell carcinoma (RCC) post nephrectomy, based on the phase 3 S-TRAC trial that showed significant improvement with SU vs placebo (PBO) in disease-free survival (DFS) based on blinded independent central review (hazard ratio [HR] 0.76; 95% confidence interval [CI] 0.59–0.98; P= 0.03). The definition of high risk in S-TRAC included both objective (T stage and Fuhrman grade) and more subjective (pre-nephrectomy Eastern Cooperative Oncology Group performance status [ECOG PS]) prognostic parameters. To delineate the highest risk pts from S-TRAC purely based on objective parameters, we performed an additional analysis classifying pts at highest risk of recurrence post nephrectomy, defined as T3 and Fuhrman grade > 2 or T4 or N+ and any T. Methods: DFS analyses were conducted using Cox proportional hazard model. Results: In S-TRAC, 398 (65%) patients were classified at highest risk. The results indicated a treatment benefit in DFS by independent review for SU vs PBO in this highest risk group (HR 0.73; 95% CI 0.54–0.97; P= 0.03), consistent with the HR for DFS previously reported in the S-TRAC trial for the T3 higher (HR 0.74; 95% CI 0.55–0.99; P= 0.04) group defined as T3 with Fuhrman grade ≥2 and ECOG PS ≥1 or T4 with any ECOG PS or N+ with any T, any ECOG PS, as well as with the overall population. Safety data did not identify major differences between the highest risk group vs overall S-TRAC pts. Incidence of key adverse events with SU was similar in highest risk group vs overall study pts (diarrhea: 58.2% vs 56.9%; palmar-plantar erythrodysesthesia syndrome: 51.5% vs 50.3%; hypertension: 35.7% vs 36.9%; fatigue: 37.2% vs 36.6%; hypothyroidism: 15.3% vs 18.3%). Conclusions: The clinically meaningful treatment benefit observed in pts at highest risk of recurrence and the overall S-TRAC population, together with a consistent safety profile between these groups, support the favorable benefit/risk assessment of SU as an adjuvant treatment option for pts with RCC at high risk of recurrence post nephrectomy. Clinical trial information: NCT00375674.
Transanal versus laparoscopic total mesorectal excision for low rectal cancer: A multicenter randomized phase III clinical trial (TaLaR trial) protocol.
Authors: Shuangling Luo, Jianping Wang, Liang Kang, Wenhao Chen
Journal: Journal of Clinical Oncology (2017)

TPS3631 Background: Since 1982, Total Mesorectum Excision (TME) was regarded as a golden standard for radical resection of rectal cancer. Current evidences have proved that both open and laparoscopic TME could achieve the comparative oncological safety. However, for low rectal cancer, it remains a challenge to achieve complete TME with safe resections margin by the conventional transabdominal approach, especially in cases such as bulky mesorectum, enlarged prostate, narrow pelvic floor, etc. Transanal TME (TaTME) is a new approach for rectal cancer. Several retrospective studies have showed its advantage of providing better resection quality for low rectal cancer compared with transabdominal approach, but its long-term effect still needs to be explored. Methods: TaLaR trial is an open-label multicenter randomized controlled phase III trial with a non-inferiority design, aiming to compare the short and long term effect between TaTME and laparoscopic TME (lapTME) for low rectal cancer. Patients diagnosed with clinical stage no more than T3N0 or ycT3N2 rectal cancer, inferior border of the tumor from anal verge less than 7cm, are eligible for the present study. A total of 1114 patients (557 per group) will be randomized to either TaTME or lapTME. The primary end-points are 3-year disease-free survival (DFS) and 5-year overall survival (OS). The secondary endpoints include resection quality, postoperative morbidity and mortality, pelvic function and quality of life. Clinical trial information: NCT 02966483.