tbuckley/cabot-search huggingface dataset:
Prognostic value of event-free survival at 24 months for adolescent and adult T-cell lymphoblastic lymphoma.
Authors: Haizhu Chen, Yuankai Shi
Journal: Journal of Clinical Oncology (2020)

e20042 Background: T-cell lymphoblastic lymphoma(L-LBL) has an aggressive clinical behavior. To date, powerful and consistent prognostic factors have not been established for adolescent and adult T-cell lymphoblastic lymphoma. In this study, we firstly evaluated the prognostic value of event-free survival (EFS) at 24 months (EFS24) for adolescent and adult T-LBL. Methods: Between January 2006 and December 2017, 91 adolescent and adult patients (aged≥12 years) with newly diagnosed T-LBL and treated with chemotherapy were retrospectively analyzed. EFS was defined as the time from initial diagnosis to relapse or progression, retreatment, death from any cause, or to the last follow up. Subsequent OS was defined as time from achieving EFS24 or time from progression in patients who did not achieve EFS24 to death from any cause or last follow-up. Results: In total, 91 patients with previously untreated T-LBL who had a median age of 24 years were enrolled. At a median follow-up of 40.4months (range, 1.4 to 163.3 months), the 5-year OS and EFS was 47.9% and 45.5%, respectively. Of all patients, 45(49.5%) achieved EFS24 and 46(50.5%) did not. EFS24 was associated with a markedly superior outcome, compared with no achievement of EFS24(5-year OS, 90.5% vs 3%). In addition, the median subsequent OS for patients achieving EFS24 was not reached (5-year subsequent OS, 84.9%), whereas median subsequent OS for patients without achieving EFS24 was only 5.5months (5-year subsequent OS, 2.7%). Multivariate analysis demonstrated that only response to treatment (CR vs no CR) was significantly associated with EFS (HR =0.219,95% CI 0.118-0.404, P &lt; 0.001), and EFS24 achievement was an independent prognostic indicator for OS (HR = 0.044, 95% CI 0.016-0.120, P &lt; 0.001). Conclusions: We confirm that EFS24 is an independent prognostic factor for OS, which can aid clinicians in discussions of risk stratification and in selection of subsequent treatments. Further validation in the context of directed prospective clinical trials is warranted.
Survey of lower urinary tract symptoms of benign prostatic hyperplasia in outpatient department for urological patients in 14 Chinese cities
Authors: Jianlong Wang, Yaoguang Zhang, Ben Wan
Journal: BMJ (2015)

Objective
To evaluate the diagnostic and therapeutic status of lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) in urological outpatients.


Methods
The survey was conducted at 57 urological clinics in 14 cities during the period of October-December 2011. All surveyed male outpatients were inquired about whether there was a history of LUTS/BPH or not. Then eligible patients received a more detailed questionnaire for LUTS.


Results
Among a total of 6 200 male outpatients, 47.4%(n=2 940) had a history of LUTS/BPH. The rate for LUTS was 30.0% (n=882) in patients aged under 40 years and 60.0%(n=1 764) in those aged over 60 years. The major complains included frequency (72.0%), urgency (53.0%) and nocturia (48.0%). At a rate of 63.0%, the patients aged 71-80 years came more to a hospital for nocturia than 61-70 years (52.0%) and 51-60 years (49.0%). The average International Prostate Symptom Score (IPSS) was 14.98(6-35) and 59.0% patients had moderate symptoms and 26.0% severe symptoms. The average score of quality-of-life was 4.12(1-6) points. And the average overactive bladder symptom score (OABSS) was 5.78(3-15) points and 56.0% patients had moderate overactive bladder (OAB) and 3.0% severe OAB. Urinalysis was largely normal. The main causes for LUTS included OAB (25.2%), BPH and OAB (20.4%), BPH (20.2%), prostatis (20.2%) and urinary infection (11.8%).


Conclusions
LUTS and BPH are common in urological outpatients. And the incidence is rising yearly. Clinical examinations and drug regimens should be timely adjusted according to the etiology. And patient education should be strengthened at the same time.


Key words: 
Prostatic hyperplasia; Lower urinary tract symptoms; Survey
Innovations in retinoblastoma treatment and reflection to enucleation rate of 362 eyes of 262 CASES: Twenty years retrospective assessment at Ankara University.
Authors: Emel Cabi Unal, Hande Tosun, Nurdan Tacyildiz, Handan Dincaslan, Kaan Gunduz, Kivilcim Yavuz, Gulsah Tanyildiz, Gulsan Yavuz
Journal: Journal of Clinical Oncology (2020)

e22509 Background: Enucleation used as the first-line tx option for RB, dx in advanced stages. Methods: To evaluate the enucleation rates of RB cases in 20 years period, to emphasize the recent developments in the tx of RB that contribute to the improvement of tx outcomes. Results: 262 patients, with the dx of RB between June 1998 &amp;December 2018 in Ankara University Departmant of Pediatric Oncology were evaluated retrospectively. The M / F ratio was 1.2, mean age at dx 19.39 mos; 22.7 mos for unilateral &amp;14.1 mos for bilateral dx. 61.8% of the patients had unilateral, 38.2% bilateral RB. 362 eyes were evaluated, 12.5% of the patients had a family history of RB bilateral dx was more frequent. The initial findings were leucocori in 58%&amp; strabismus in 27.9%, similar to the literature. According to ICRB, 6% of the patients were diagnosed in Group A, 22% in Group B, 19% in Group C, 22% in Group D and 31% in Group E. Patients with bilateral dx were diagnosed at an earlier stage. Enucleation, in 50.5% of 362 eyes analyzed. There was no enucleated eye in Group A. In group B,10.1% of the eyes were enucleated, as of recurrence. 32.3% of eyes in Group C, 60.7% of eyes in Group D and 92.9% of eyes in Group E were enucleated. Enucleation was performed in 25.4% of the eyes within the first month after dx as of the advanced stage. 33.7% of of the eyes who did not have enucleation at the time of dx required enucleation at FU. The most common causes of enucleation were tumor recurrence, total retinal detachment &amp; vitreous hemorrhage. The tx methods other than enucleation are systemic CT, RT &amp; local treatments; cryotherapy, thermotherapy, episcleral brachytherapy, intravitreal CT &amp; intraarterial CT. Systemic CT applied to 77% of the patients.CT protocol were VEC and ICE.RT was applied to 17% of the patients. After 2012, radiotherapy was used only in 2 patients with systemic involvement. Cryotherapy was performed in 48.3% of the eyes, thermotherapy in 38.6%, episcleral brachytherapy in 3.8% of the eyes included.Intraarterial CT to be used after 2004 was applied to 16.6% of eyes dx &amp; intravitreal CT was used after 2009 was applied to13.2% of eyes. Enucleation was avoided in 84.6% of eyes in which these two tx modalities were applied together. Enucleation rates of 56.3% &amp;61.2% between 1998-2004 and 2004-2009, respectively; with active use of intraarterial and intravitreal CT, decreased to 40.2% between 2009-2018. Conclusions: It was observed that enucleation rates &amp;RT gradually decreased with using systemic CT and local treatment methods.
Comprehensive analysis of long noncoding RNA expression in circulation of breast cancer patients on neoadjuvant therapy.
Authors: Boris Krastev, Constanta Timcheva, Spartak Valev, Georgi Zhbantov, Ivaylo Stoykov, Georgi Stamenov
Journal: Journal of Clinical Oncology (2020)

e12644 Background: Though long considered “nonfunctional”, recent evidence is growing that non-coding RNAs, including long non-coding RNAs (lncRNAs), have an active role in tumor biology, mainly as gene expression regulators. Breast cancer is heterogeneous in nature and locally advanced cases are distinct entity in terms of curability. Being borderline between early and metastatic disease, long-term outcome here strongly depends on the efficacy of systemic therapy. To the best of our knowledge, no study has yet investigated global changes of circulating lncRNAs in this patient population during preoperative (neoadjuvant) treatment. Methods: We conducted a small transcriptomic trial on 10 locally advanced breast cancer patients, assessing lncRNA and messenger RNA (mRNA) expression in plasma samples before (S1) and after (S2) initiation of neoadjuvant therapy. Next-generation sequencing was performed with differential gene expression analysis between S1 and S2 groups. We assessed co-expression between lncRNAs and mRNAs, identifying mRNAs whose transcription was potentially regulated by lncRNAs, i.e. “lncRNA target genes”. In order to elucidate biological roles of these target mRNAs, we performed gene ontology (GO) and pathway analysis (Kyoto Encyclopedia of Genes and Genomes, KEGG). Results: 394 lncRNAs and 1085 mRNAs demonstrated statistically significant difference in expression between pretreatment and posttreatment samples. Co-expression analysis revealed positive correlation between 25 lncRNAs and 25 mRNAs located in cis, while potential trans interactions exceeded 10 5 . GO evaluation of lncRNA target genes was significant for 44 terms: 28 for biological process (BP), 9 for cellular component (CC) and 7 for molecular function (MF). The most annotated terms for BP, MF and CC were respectively biosynthetic process, DNA-binding transcription factor activity and nucleus. KEGG analysis showed that 105 of 201 analyzed pathways were statistically significant with most prominent being pathways in cancer and transcriptional misregulation in cancer. Conclusions: Despite limited in size, present study provides broad view on transcriptional landscape in blood circulation, interrogating in vivo dynamics of systemic gene expression during neoadjuvant breast cancer treatment. It demonstrates that substantial number of circulating lncRNAs could be up- or downregulated in the course of therapy and this has the potential to control protein-coding genes that are tightly implicated in cancer biology.
Evaluation of thyroid-stimulating hormone-increased, hypertriglyceridemia and proteinuria as markers of anlotinib efficacy in advanced soft tissue sarcoma.
Authors: Yihebali Chi, Yang Yao, Zhiwei Fang, Shusen Wang, Gang Huang, Qiqing Cai, Guanning Shang, Guowen Wang, Guofan Qu, Qiong Wu, Yu Jiang, Jianmin Song, Jing Chen, Xia Zhu, Zhengdong Cai, Chunmei Bai, Yongkui Lu, Zhihua Yu, Jingnan Shen, Jianqiang Cai
Journal: Journal of Clinical Oncology (2020)

e23548 Background: ALTER0203 was a randomized phase IIB trial (NCT02449343) that demonstrated single-agent activity of anlotinib in advanced STS (aSTS). The primary endpoint progression-free survival (PFS) was met and presented as an oral presentation in 2018 ASCO. The most common adverse events with anlotinib were hypertension (62.66%), thyroid stimulating hormone (TSH) increased (56.33%), hypertriglyceridemia (50%), hand-foot syndrome (48.10%) and proteinuria (36.08%) similar to other vascular endothelial growth factor receptor pathway-targeted therapies. We had evaluated the anlotinib-induced hand-foot syndrome and hypertension with clinical outcome in aSTS patients previously. Here we investigated thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria on clinical outcome in aSTS patients treated with anlotinib. Methods: We conducted a review of patients enrolled in ALTER0203. Median PFS was analyzed in patients with thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria vs patients with no thyroid stimulating hormone increased, hypertriglyceridemia and proteinuria. All analyses were exploratory and required cautious interpretation. Results: A total of 158 patients received anlotinib in the ALTER0203 study. During the study, TSH increased was observed in 89 patients (56.33%). Hypertriglyceridemia was observed in 79 patients (50%). Proteinuria was observed in 57 patients (36.08%). Median PFS was longer in patients with TSH increased vs patients with no TSH increased (8.40 vs 4.23 months, p = 0.015). Patients with any grade TSH increased while on anlotinib had an adjusted hazard ratio for progression of 0.64 compared to those without TSH increased. Also, median PFS was longer in patients with hypertriglyceridemia and proteinuria vs patients with no hypertriglyceridemia and proteinuria (8.43 vs 4.13 months, p = 0.002; 8.40 vs 4.37, P = 0.048). Patients with any grade hypertriglyceridemia and proteinuria while on anlotinib had an adjusted hazard ratio for progression of 0.59 and 0.75 compared to those without hypertriglyceridemia and proteinuria respectively. Conclusions: In this retrospective analyses, TSH increased, hypertriglyceridemia and proteinuria can serve as biomarkers in aSTS patients treated with anlotinib. Clinical trial information: NCT02449343 .
Treatment intensity and risk of chronic health conditions and late mortality among long-term survivors of Wilms tumor: A report from the Childhood Cancer Survivor Study.
Authors: Brent R Weil, Daniel M. Green, Andrew J Murphy, Qi Liu, Rebecca M. Howell, Christopher Bertero Weldon, Elizabeth Anne Mullen, Arin L Madenci, Wendy M. Leisenring, Joseph Philip Neglia, Kevin C. Oeffinger, Amanda M. Termuhlen, Sogol Mostoufi-Moab, Jennifer Levine, Kevin R. Krull, Yutaka Yasui, Leslie L. Robison, Gregory T. Armstrong, Eric Jessen Chow, Saro Armenian
Journal: Journal of Clinical Oncology (2020)

10553 Background: Refinement in risk stratification has led to intensification of therapy for Wilms tumor (WT) patients with adverse prognostic factors. Chronic health conditions (CHCs) including cardiac conditions, subsequent malignant neoplasms (SMNs), and late mortality are known risks for WT survivors, however the impact of specific treatment regimens on these outcomes is largely unknown. Methods: Late mortality (all-cause and non-recurrence death &gt; 5 years from diagnosis), SMNs, and severity-graded CHCs (2 = moderate, 3 = severe, 4 = life-threatening, 5 = fatal) were assessed in 5-year WT survivors in the Childhood Cancer Survivor Study diagnosed from 1970-99. Survivors were categorized according to therapy received (Table). Cumulative incidence of mortality and standard mortality ratios (SMR) were estimated. Piecewise exponential models estimated rate ratios (RR) with 95% confidence intervals (CI). Results: Among 1507 survivors (median age at follow-up 26 yrs; range 6-55), 35-year cumulative incidence of all-cause mortality was 7.9% (SMR 2.9, CI 2.3-3.6) and 5.1% (SMR 1.9, CI 1.4-2.4) for non-recurrence mortality. RRs for developing any grade 2-5 CHC, grade 3-5 SMN, and grade 2-5 cardiac CHCs were higher for survivors compared to sibling controls (2.0, CI 1.8-2.3; 7.4, CI 5.0-10.8; 2.6, CI 2.2-3.1, respectively). Compared with VA and no RT, RR for non-recurrence late mortality and CHCs among survivors were higher for VAD + any RT, and for ≥ 4 drugs + any RT (Table). Conclusions: Administering increased-intensity therapy for WT is associated with increased late health consequences and non-recurrence late mortality, necessitating strategies to monitor and improve long-term health among survivors. [Table: see text]
Patient-derived organoids as a potential tool for clinical decision in advanced gallbladder cancer.
Authors: Javiera Obreque, Luis Vergara, Felipe Suarez, Patricia Garcia, Katherine Marcelain, Jessica Toro, Solange Rivas, Lorena Rosa, Juan Carlos Roa, Bruno Nervi, Eduardo Viñuela, Gloria Aguayo, Sabrina Muñiz-Muñoz, Nicole Caire, Anrried Escalante, Sebastian Mondaca, Carolina Bizama
Journal: Journal of Clinical Oncology (2020)

e16717 Background: Human gallbladder cancer research lacks in vitro models that can recapitulate the pathophysiology of the original tumor and normal epithelia. Organoids cultures emulate the tumor heterogeneity and have been successively used as translational models to evaluate clinical response to anticancer drug. Here, we established and characterized patients derived organoids culture (PDOs) from human gallbladder cancer patients. Methods: Fresh tissues obtained from gallbladder cancer patients who underwent cholecystectomy were digested with Collagenase/Dispase, filtered and then suspension cells were mixed with Matrigel (1:1) for organoids establishment. Cultures were maintained at 37°C and 5% CO2. The organoids were characterized through histopathology evaluation, immunohistochemistry, and ultra-deed targeted sequencing (TruSeq protocol, Illumina, TSACP; 25 genes). In addition, we evaluated the response of organoids to gemcitabine, cisplatin and Fluorouracil (5-FU), using the CellTiter-Glo 3D luminescence assay. Results: We have successfully established PDOs cultures from six patients with gallbladder adenocarcinoma with a 60% efficiency (6/10). The PDOs recapitulated the histological features and maintained the expression of CK19, Ki67, P53 as compared with the epithelia of primary tumors. Moreover, the PDOs maintained the mutational status of major driver genes, including TP53 and PIK3CA. Finally, tumor organoids showed differential response to standard chemotherapy treatment. GBC-PDO2 and GBC-PDO4 showed high resistant to gemcitabine (IC50 &gt; 10μM), which suggests that the personalized treatment is necessary for generate better response. Conclusions: the established gallbladder tumor organoids exhibited similar histological and genomic features in relation to their original epithelia. PDOs can be considered a valuable tool for future research aimed to understand gallbladder cancer biology and for developing personalized-medicine approaches for advanced gallbladder cancer patients. (Funding Source: FONDECYT #1171463, FONDECYT #1170893 and Fondef IT16I10051).
Impact of bolus versus continuous infusion of doxorubicin (DOX) on cardiotoxicity in patients with breast cancer (BC) and sarcomas: Analysis of real-world data.
Authors: Lee D. Cranmer, Lisa M. Hess, Tomoko Sugihara, Yajun Emily Zhu
Journal: Journal of Clinical Oncology (2020)

e19123 Background: Doxorubicin continues to play a central role in management of breast cancer and sarcomas. Dose-dependent cardiomyopathy is a challenge in its use. Strategies have been proposed to mitigate this, including administration by continuous intravenous (CIV) infusion as an alternative to bolus (BOL) administration. This study used real world data to explore the impact of DOX administration mode on cardiotoxicity, duration of DOX and time to treatment failure (TTF). Methods: This study used IBM MarketScan claims to identify patients age ≥ 18 who received at least 2 DOX administrations after cancer diagnosis. Patients with history of cardiac events/toxicities were excluded. Cardiac events were compared for BOL versus CIV overall, by tumor site and by regimen during three follow-up periods, early (within 1 year), middle (&gt;1 to 5 years) and late (&gt;5 years), from DOX initiation using Fisher’s exact test. Duration of DOX and TTF, defined as time from initiation of DOX to subsequent systemic therapy, hospice or death, were evaluated using Kaplan-Meier method and unadjusted Cox proportional hazards models. Results: 62,597 patients were eligible, including 38,961 with BC and 1,772 with sarcoma. Most patients had codes for both modes; 1,941 and 7,094 patients had exclusive BOL and CIV codes, respectively. For these patients, mean duration of DOX was longer for BOL vs. CIV (83.9 vs. 65.4 days, p&lt;0.001). Cardiac events for BOL vs. CIV were 6.5% vs. 5.6% (p=0.098) during the early period, 4% vs. 5.1% (p=0.046) middle period, and 0.5% vs. 0.9% (p=0.068) late period. This pattern was consistent for BC and sarcoma and among those who were pre-treated. There were no differences in cardiac events for BOL vs. CIV for the chemotherapy naïve or DOX monotherapy groups (all periods p&gt;0.10) but statistically different for the breast during the middle period, sarcoma at any time, and pretreated subgroup middle period (all p&lt;0.05). TTF favored CIV over BOL among patients with BC (p&lt;0.0001) but BOL over CIV in sarcoma (p=0.002). TTF was not significantly different between BOL and CIV for BC monotherapy (p=0.067) but was significant for sarcoma monotherapy favoring BOL administration (hazard ratio 0.72, 95% confidence interval 0.54-0.95, p=0.02). Conclusions: These data suggest that cardiac events may occur at a similar rate irrespective of mode of DOX administration. Further analyses are needed to understand how these relationships are impacted by other potential risk covariates (eg, age, gender) and by protective factors (eg, dexrazoxane).
Marital status and suicide as a competing cause of mortality among cancer survivors.
Authors: Nosayaba Osazuwa-Peters, Matthew C Simpson, Eric Y Du, Scott A Hong, Aleksandr R Bukatko, Eric Adjei Boakye, Mark A Varvares
Journal: Journal of Clinical Oncology (2020)

e19113 Background: The risk of suicide among cancer survivors more than double that of the general population, highlighting the need to mitigating risk factors for suicide. While several studies have described marital status, a surrogate for social support, as associated with cancer mortality, it is inconclusive whether marital status impacts suicide as a competing cause of cancer mortality. We tested this hypothesis by describing the association of marital status and suicide among survivors of four cancer sites with the highest suicide mortality rates in the United States. Methods: Adult cancer patients were identified from the Surveillance, Epidemiology and End Results database from 2004 to 2016 for four index cancer sites previously identified with highest suicide mortality rates: pancreas, head and neck, lung/bronchus and stomach ( n = 800,798). Cumulative incidence curves stratified by marital status (divorced/separated, widowed, never unmarried, and married/partnered) estimated unadjusted probability of suicide (outcome of interest). A multivariable competing risk proportional hazards model yielded sub-distribution hazard ratios (sdHRs) and 95% confidence intervals (CI) to estimate the association of marital status with suicide for each cancer site, while controlling for clinical and nonclinical factors. Results: Half (50.7%) of the cohort were married/partnered, males (56.8%), and non-Hispanic whites (71.0%). Mean age at diagnosis was 67.3 years. Most patients (60.9%) had cancer in the lung/bronchus, 17.9% head and neck, 13.8% pancreas, and 8.3% stomach. Unadjusted probability of suicide was highest among head and neck cancer survivors (0.3%). In the fully adjusted model, mortality by suicide was more likely among divorced/separated patients vs. married/partnered patients across cancer sites (sdHR head and neck = 1.81; 95% CI 1.38, 2.37; sdHR lung/bronchus = 1.68; 95% CI 1.28, 2.19; sdHR pancreas = 2.19; 95% CI 1.27, 3.78; and sdHR stomach = 2.38; 95% CI 1.17, 4.58). Additionally, for lung/bronchus cancer, patients who were never married patients were more likely to die by suicide than those married/partnered (sdHR lung/bronchus = 1.47; 95% CI 1.09, 1.98). Conclusions: Marital status is associated with suicide mortality among cancer survivors, and divorced/separated survivors may have greater suicide mortality risks, independent of cancer site. As overall probability of suicide remains low, these findings might help identify cancer survivors who may be candidates for ongoing surveillance and psychosocial support to mitigate suicide mortality risks.