bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of percentage of squamous differentiation in patients with nonbilharzial squamous cell carcinoma and transitional cell carcinoma treated with radical cystectomy.
Authors: Slim Marine , Comperat Eva , Roupret Morgan , Parra Jerome , Simon Jean-Marc , Khayat David , Bitker Marc-Olivier , Spano Jean-Philippe , Malouf Gabriel G. 
Published: February 2018

498 Background: Squamous differentiation has been reported to occur in 10-22 % of transitional cell carcinoma. The prognostic impact of squamous differentiation is controversial. In addition, it remains unclear whether the percentage of squamous differentiation impact outcome of patients with nonbilharzial squamous cell carcinoma and transitional cell carcinoma treated with radical cystectomy Methods: We performed a retrospective study of patients with non-bilharzial squamous variants or squamous bladder carcinoma treated in two French institutions. The percentage of squamous differentiation was determined by an expert GU pathologist on radical cystectomy specimens. Progression-free survival (PFS) and cancer-specific survival (CSS) were analyzed according to the percent of squamous differentiation. Survivals were estimated using the Kaplan-Meier method and compared using multivariate Cox proportional hazard regression analysis. Results: Forty patients were identified including 28 and 12 patients which tumors were classified as transitional cell carcinomas cases with squamous cell differentiation and pure non-bilharzial squamous bladder carcinoma, respectively. Patients with tumors harboring more than 50% of squamous differentiation had a PFS of 6.3 months as compared to 60.2 months for those with squamous differentiation present in less than 50% (p = 0.014). In multivariate analysis, the percentage of squamous differentiation was the only independent prognostic factor for PFS (HR = 2.63 (IC 95%: 1.22-5.67). First site of recurrence of patients with squamous differentiation ≥50% were more frequently the pelvis (72% versus 17 %; p = 0.049). No difference in CSS were observed between patients with tumors < 50% or ≥50% squamous differentiation (16.3 months versus 62 months) (p = 0.2). Conclusions: Extensive squamous differentiation in bladder cancer is associated with poor PFS and pelvic progression, suggesting that those patients might benefit from adjuvant pelvic radiotherapy. Larger studies are needed to validate these findings.
Hypoxia related mRNA biomarker to predict biochemical failure and metastasis for prostate cancer.
Authors: Choudhury Ananya , Yang Lingjian , Roberts Darren , Takhar Mandeep , Vinayak Bhandari , Bibby Becky , Cheng Wei-chen , Haider Syed , Thiruthaneeswaran Niluja , Hoskin Peter , McArt Darragh , Jain Suneil , Buffa Francesca Meteora , Erho Nicholas , Bristow Robert G. , Boutros Paul Christopher , Davicioni Elai , West Catharine 
Published: February 2018

5 Background: Hypoxia is an important regulatory factor in tumorigenesis and is associated with a poor prognosis. Patients with high risk locally advanced disease account for 13-21% of prostate cancer cases and the ten year cancer specific survival rate for these patients is 62%. Patients with hypoxic tumours could benefit from hypoxia modifying therapeutics in addition to radiotherapy. Clinical companion biomarkers are needed to stratify patients who would benefit from hypoxia modifying therapy in addition to radiotherapy. Methods: RNA-seq analysis was performed on prostate cell lines (PNT2-C2, PC-3, LNCaP and DU145) exposed to 1% hypoxia for 24 hrs. A prostate cancer hypoxia gene signature was derived in silico using publicly available prostate gene expression data sets and the RNA-seq data. The biomarker was then independently validated in multiple cohorts of prostate cancer patients with localized diseases receiving prostatectomy alone, prostatectomy plus adjuvant radiotherapy, prostatectomy plus salvage radiotherapy, or definitive radiotherapy alone. Results: In vitro the hypoxia inducible expression of the hypoxia gene signature was tested at 1% and 0.1% oxygen of which 21 of the 28 genes were regulated by hypoxia. Patients stratified as high hypoxia were associated with significantly poorer 5-year biochemical recurrence free survival in patients undergoing prostatectomy alone, prostatectomy plus adjuvant radiotherapy and definitive radiotherapy alone. In multivariable analysis, the biomarker retained significance after correcting for confounding factors including Gleason group, PSA, a molecular classifier, etc. In another cohort of prostatectomy and salvage radiotherapy treated patients, the mRNA signature predicts metastasis free survival in both univariable and multivariable analyses. Conclusions: We derived a de novo mRNA signature based on hypoxia-regulated genes. The biomarker consistently predicts biochemical failure and metastasis for prostate cancer patients with localized disease.
Managing low risk prostate cancer: A cost analysis.
Authors: Gaylis Franklin , McGill Kevin , Levy Susan S , Ball Catherine E , Prime Hillary , Dato Paul , Cohen Edward ,   ASCO Authors' Group
Published: February 2018

50 Background: Healthcare costs in the US continue to rise at an unsustainable rate. Prostate cancer (PCa) accounts for 21% of all new cancer cases in men and is predicted to incur a cost of $18.53 billion in the next few years. In this study we examined the costs associated with managing low-risk PCa with traditional treatment options compared to Active Surveillance. Methods: One hundred ninety-five patients were identified as NCCN defined low-risk PCa (Gleason score ≤ 6, PSA < 10, clinical stage T1c to T2a) between January 1, 2012 to June 30, 2013 at Genesis Healthcare Partners (GHP). Ninety three (48.7%) patients had at least 3 years of follow-up care and formed the cohort for analysis. Treatment paths analyzed included active surveillance (AS), radical prostatectomy (RP), stereotactic body radiation therapy (SBRT) and intensity-modulated radiation therapy/image-guided radiation therapy (IMRT/IGRT). Patients’ charts were examined for all episodes of care during the three-year period subsequent to their first positive biopsy and cost attribution to each episode was based on a cost-to-Medicare perspective using the Medicare Physician Fee Schedule (MPFS) for GHP. Total and annual costs of care were compared for patients followed for a 3-year period using one-way analysis of covariance (ANCOVA), covarying for patient age and Charlson Comorbidity Index (CCI). Results: Active surveillance ($4,072 ± $1354) compared to RP ($9,972 ± $1571), SBRT ($26,294 ± $2049), and IMRT/IGRT ($40,438 ± $2091) had significantly lower total 3-year costs ( p < .001, ɳ² = .44) compared to those in the other treatments group. Specific characteristics of the AS cohort’s treatment path included an average number of biopsies of 2.0 ± 0.8 and only six (21%) patients had at least one MRI performed during their treatment path. Active surveillance with a more costly genomic study (n = 4) incurred a cost of $9,475 ± $1456 over three years. Conclusions: Active surveillance may be considered a beneficial management strategy for low-risk PCa from a cost perspective. The cost effective benefit as well as the avoidance of treatment (surgery, radiation therapy) related side effects, support its consideration as a value-based care model, the primary goal of the Medicare Access and Chip Reauthorization Act.
Role of mTORC2 and nitric oxide in bladder cancer invasion.
Authors: Sahu Divya , Hansel Donna E. , Klemke Richard , Boss Gerry 
Published: February 2018

504 Background: In the United States, bladder cancer is the fourth most common cancer, with an estimated 79,000 new diagnoses and 17,000 deaths in 2017, and the eleventh most common cancer worldwide. The key driver of bladder cancer stage progression is tumor cell invasion which has limited response to current chemotherapy options and hence, newer therapies directed against invasion are key to improving the treatment of bladder cancer. Our laboratory has identified mammalian target of rapamycin complex 2 (mTORC2) as a driver of bladder cancer cell invasion. We have also recently shown that arginine, the nitric oxide (NO) precursor, is implicated in bladder cancer progression. We evaluated the interaction between these two pathways to promote invasion. Methods: Expression of inducible and endothelial nitric oxide synthases (iNOS and eNOS) in FFPE tissue sections of progressive disease was assessed by IHC and correlated with histopathology, progression and stage based on moderate to strong expression (2+, 3+) compared to absent to weak expression (0, 1+).We utilized gene silencing methods and NOS inhibitors and NO scavenger for effects on bladder cancer invasion and migration. We assessed mTORC2 pathway activity and NOS levels in invasive cell tip protrusions called “invadopodia” and evaluated if mTORC2 regulates NOS localization and/or activity. We used a novel zebrafish model to characterize the effects of mTORC2 and NO on bladder cancer metastases. Results: We found that eNOS and iNOS are elevated in invasive human bladder tumors and cell lines and their ablation reduces bladder cancer cell migration and invasion. mTORC2 silencing can affect levels of iNOS and eNOS in bladder cancer cell lines. Silencing of mTORC2, eNOS or iNOS reduced metastases of bladder cancer cells within zebrafish. Conclusions: mTORC2 pathway is a key driver of bladder cancer invasion and metastases by regulating the NO pathway and both mTORC2 and NO can be targets for bladder cancer therapy, which would benefit patient outcomes.
Molecular characterization of brain metastases in patients with metastatic urothelial cancer.
Authors: Nizam Amanda , Trump Donald L. , Aragon-Ching Jeanny B. 
Published: February 2018

509 Background: Urothelial cancers are the 6th most common cause of all new cancer cases in 2017. Metastatic disease to the brain is rare but has a poor prognosis. There is little information regarding the phenotypic and molecular characteristics of urothelial cancers involving the brain. We sought to evaluate the clinical and tumor molecular characteristics in patients with metastatic urothelial cancer to the brain. Methods: In a single institution retrospective chart review, 48 patients were found to have metastatic bladder cancer from 2006 to 2015, 4 had brain metastases. The demographics, stage, phenotypic characteristics and molecular characteristics using Oncomine, a cancer microarray platform targeting 143 cancer genes, was determined. Results: Of the 4 patients identified with metastatic brain urothelial cancer, 3 were men. 2 had both upper tract and bladder urothelial cancers and 2 had bladder cancer alone. 3 had prior nephroureterectomy and/or radical cystectomy initially and had subsequent development of initial distant metastases at a median of 7.9 months, and time between the first to brain metastases at a median onset of 11.8 months. Median overall survival (OS) was short upon diagnosis of brain metastasis with a median OS of 119 days (range: 96 – 391 days) from the time of brain metastasis diagnosis. All received surgical resection followed by radiation for brain metastases. Three patients had brain tumor examined for comprehensive somatic tumor profiling using the Oncomine panel. Results showed APC mutation in patient 1, loss of TP53, BRCA-2 loss of function mutation with MSH2 deletion in patient 2, as well as FGFR3 gene mutation and TP53 mutation in patient 3. All patients received prior platinum-based systemic therapy with additional FGFR3-therapy for patient 3 and atezolizumab for patient 4. Conclusions: Metastatic brain urothelial cancers are rare events with a uniformly poor prognosis. The role for targeted therapy and immunotherapy is still evolving.
CT-based texture characterization of lymphadenopathy in urothelial carcinoma: Prediction of treatment response.
Authors: Tejura Tapas K , Quinn David , Varghese Bino , Cen Steven Yong , Hwang Darryl , Chen Frank K , Desai Bhushan , Fan Ting-Wei , Duddalwar Vinay 
Published: February 2018

514 Background: Promising treatments are emerging for urothelial carcinoma, although there is no reliable method for predicting treatment response on an individual basis. Extraction of quantitative tumor-texture features from clinical radiologic images may distinguish between cancers which may be more responsive to treatment. Our purpose is to analyze CT-based textural features of urothelial cancer lymph node metastases prior to treatment and classify them to categories for response. Methods: In this IRB approved retrospective study, 36 patients with a proven diagnosis of urothelial cancer who were scheduled to have chemotherapy (Eribulin) and had pre- and post-treatment imaging were included. A total of 66 abnormally enlarged lymph nodes (> 1.5 cm short-axis) were identified. Using RECIST 1.1 as treatment standard, lymph nodes were categorized into 3 categories: Complete or partial response (CR, PR), Stable disease (SD), and Progressive disease (PD). Texture analysis was performed using six different textural methods ranging from 1st order statistical methods such as histogram analysis to higher-order methods such as image-frequency analysis. Depending on data normality, ANOVA or Kruskal Wallis test were used to assess signal difference across CR/PR, SD, and PD categories univariately. Classification Tree (CART) was used to explore potential multivariate prediction model. Results: 34 lymph nodes were categorized as CR/PR, 19 categorized as SD, and 13 categorized as PD. Univarate data analysis showed that of the various textural, histogram-based metrics: Correlation, Variance, Standard deviation, Sum/difference of averages, Homogeneity/Dissimilarity have statistically significantly difference across response categories (p<0.05). CART analysis show preliminary evidence of predicting PD with 85% sensitivity but 54% false positive. Conclusions: CT-based textural features can differentiate between urothelial cancers which are more likely to respond to treatment. Validation with larger sample size and inclusion of data from other sites of metastases will aid in the identification of reliable imaging-texture based biomarkers for treatment stratification.
Survival after surgical or radiotherapeutic treatment for high-risk localized prostate cancer: A National Cancer Database analysis with comprehensive treatment group imbalances adjustments.
Authors: Ennis Ronald D. , Hu Liangyuan , Ryemon Shannon Nicole , Lin Joyce , Mazumdar Madhu 
Published: February 2018

55 Background: There are no randomized trials to guide a high-risk localized prostate cancer patient’s treatment decision between radiotherapeutic and surgical options. Comparative studies have been limited by their ability to match patients based on pre-treatment prognostic variables and to adjust for the cancer–related, medical and socioeconomic differences between patients who choose radiotherapeutic or surgical approaches. Methods: We analyzed the outcome of all patients in the National Cancer Database with high-risk clinically localized prostate cancer with complete prognostic data who were treated with either radical prostatectomy (RP), external beam radiotherapy (EBRT) combined with androgen deprivation (AD) or EBRT+brachytherapy (brachy)±AD. Inverse probability of treatment weighting (IPTW) was used to adjust for covariate imbalance between treatment groups. Time-dependent Cox proportional hazards (TDCPH) model was then used to evaluate differences between treatment groups. Because of imbalances in the frequency of pathologic lymph node sampling between the treatment groups, a predictive model of pathologic nodal (pLN) status was built using PSA, Gleason score and clinical T stage and predicted pLN status was used to repeat the IPTW and TDCPH model. Results: 42,765 patients were analyzed. There was no statistically significant difference in survival between RP and EBRT+brachy±AD (HR 1.17 (0.88, 1.55)). However, EBRT+AD was associated with higher mortality than RP (HR 1.53 (1.22, 1.92)). Adjustment for predicted pLN status did not change the results. Subset analysis of EBRT+AD patients who received ≥7920 cGy narrowed the difference but remained significant (HR 1.32 (1.02, 1.66)). Conclusions: After comprehensively adjusting for imbalances in prostate cancer prognostic factors, other medical conditions and socioeconomic factors, this analysis showed no difference in survival between patients treated with RP vs. EBRT+brachy±AD. EBRT+AD was associated with lower survival. Randomized trials comparing these three methods of treatment are urgently needed.
Impact of Medicaid expansion on diagnosis and management of patients with testicular cancer.
Authors: Shen Xinglei , TenNapel Mindi 
Published: February 2018

551 Background: One crucial aspect of the Affordable Care Act is the optional Medicaid expansion, which started in 2014. Patients with testicular cancer may derive particular benefit from Medicaid expansion due to demographics overlap. We hypothesize that Medicaid expansion would improve outcome in these patients. Methods: We reviewed the Surveillance Epidemiology and End Results (SEER) database for testicular cancer diagnosed from 2010 to 2014. Among the SEER regions, we separated in to states that did (CA, CT, HI, IA, KY, MI, NJ, NM, WA) or did not (AK, GA, LA, UT) undertake expansion. Medicaid data from CMMS were used to measure the degree of Medicaid expansion (EXP). Data from 2010-2013 was used as baseline, and 2014 as the effect of EXP. Chi-square test was used to compare between groups. Results: We identified 12731 cases of testicular cancer from 2010 to 2014. Within SEER regions, overall Medicaid enrollment increased by 30.4% from 2013 to 2014 in the EXP states, and by 8.4% in non-EXP states. Expansion did not affect incidence of testicular cancer. In the EXP states, Medicaid coverage for testicular cancer increased from 14.8% to 19.4% in 2014 (p < 0.001) and uninsured decreased from 8.7% to 4.3% (p < 0.001). In non-EXP states, coverage with Medicaid (9.7% to 8.8%, p = 0.60) and uninsured (13.6% to 12.9%, p = 0.68) did not change. Within individual states, we noted a linear correlation between % increase in Medicaid enrollment and % decrease in uninsured cases (R = 0.58). Among Medicaid patients in EXP states, stage I cases increased (52% to 60%), stage III cases decreased (27% to 20%). There was no change among insured patients (70.6% to 73.3% for stage I, and 10.9% to 9.1% for stage III). In contrast, in non-EXP states, Medicaid patients had decrease in stage I and increase in stage III cases. Medicaid patients had higher rates of no treatment and lower rates of lymph node assessment for stage II NSGCT compared to insured patients, but this did not vary with EXP. Conclusions: Medicaid expansion reduced rate of uninsured for patients with new diagnosis of testicular cancer. There was a shift to earlier stage of diagnosis in Medicaid patients, but no apparent effect yet on management. Future studies will focus on change over time and effect on survival.
Diagnostic radiation and testicular germ cell tumor risk.
Authors: Nead Kevin Thomas , Mitra Nandita , Weathers Benita , Pyle Louisa T , Nathanson Katherine L. , Kanetsky Peter A 
Published: February 2018

556 Background: Both incidence of testicular germ cell tumor (TGCT) and use of diagnostic radiation have increased in recent decades. In a quarter of diagnostic scans in children, direct and indirect radiation dose to the testes exceeds 20 mSv, which surpasses thresholds associated with malignancy risk (~5 mSv). Here, we examine the association between exposure to diagnostic radiation and TGCT risk in a case-control study. Methods: Cases were enrolled in a hybrid hospital- and population-based setting and controls were recruited from the community. Participants reported on exposures to x-ray/CT below the waist and lower GI series, and we derived a combined variable for any exposure. After imputation to infer missing data, we compared baseline characteristics and used multivariable logistic regression adjusting for age and race to determine the risk of developing TGCT according to number of exposures and age at first exposure. Results: As expected, cases (n = 1088) were more likely than controls (n = 1458) to be white, have a family history of TGCT, and have a history of cryptorchidism (p < 0.05). There was an increased risk of TGCT with a greater number of exposures for both x-ray/CT (ptrend= 0.002) and the combined diagnostic radiation variable (ptrend< 0.001). Compared to those without any exposure, risk was greatest among those reporting ≥6 exposures for x-ray or CT (OR, 9.6; 95% CI, 4.6-19.9; p < 0.001) and the combined variable (OR, 5.8; 95% CI, 3.2-10.4; p < 0.001), after adjusting for age at first exposure. Early first exposure before eleven years of age increased risk of TGCT for x-ray/CT (OR, 2.36; 95% CI, 1.17-4.77) and combined radiation exposure (OR, 1.96; 95% CI, 1.05-3.67) compared to later first exposure after seventeen years of age, adjusting for total exposures. Analyses limited to observed data only yielded similar results. Conclusions: Exposure to diagnostic radiation below the waist, particularly among younger individuals, may increase TGCT risk. These results should be validated. As the testes are present outside the body and rarely examined using diagnostic radiation, a unique opportunity for shielding exists. Efforts to reduce testicular dose and optimize shielding practices should be prioritized.
Glypican 3 (GPC3) expression in a lethal subgroup of refractory cisplatin-resistant testicular germ cell tumor (TGCT).
Authors: Chahoud Jad , Zhang Miao , Lin Song-Chang , Lin Sue-Hwa , Tu Shi-Ming 
Published: February 2018

559 Background: The oncofetal protein GPC3 has been tested as a therapy target. Early phase clinical trials established the safety and efficacy of anti-GPC3 chimeric antigen receptor modified T cells in patients with refractory or relapsed GPC3+ hepatocellular carcinoma. In TGCT, GPC3 is preferentially expressed at presentation in certain germ cell histological phenotypes (yolk sac tumor [YST], choriocarcinoma), but not in others (embryonal carcinoma, teratoma, seminoma). The aim of this study is to evaluate GPC3 expression in a lethal subgroup of refractory cisplatin-resistant TGCT. Methods: We retrospectively evaluated 615 patients diagnosed with TGCT from January 2000 to December 2010. We identified patients who died from their TGCT. The histologic makeup of primary tumors, next-generation sequencing data and the clinical course of disease were determined for each patient. We prospectively evaluated GPC3 expression by immunohistochemistry (IHC) using a mouse monoclonal antibody (YP7), on tumor tissue from these patients with lethal, heavily pretreated, cisplatin-resistant TGCT. Results: We identified seven patients with fatal and cisplatin-resistant TGCT, with a median age of 30 (28-50) years and a median number of prior therapies of 5 (2-8), including 3 patients who received high-dose chemotherapy with autologous stem-cell transplant. The prospectively collected samples were from different sites of metastasis: lymph nodes (n = 4), peritoneal carcinomatosis (n = 2), and lung (n = 1). The tissue histology comprised YST (n = 2), YST + choriocarcinoma (n = 1), YST + teratoma (n = 1), teratoma (n = 1), and somatic transformation (n = 2). No consistent genetic aberration was detected. The viable germ cell tumor components comprising YST and choriocarcinoma (n = 4) stained strongly positive in a membranous distribution for GPC3. While samples with teratoma and somatic transformation histology (n = 3) did not stain for GPC3. Conclusions: Potentially lethal, heavily pretreated, cisplatin-resistant viable germ cell tumors have enhanced expression of GPC3. Targeted therapy directed against GPC3 could benefit patients harboring such tumors and further investigation is of value.