bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between circulating tumor DNA (ctDNA) detection and radiographic tumor burden (rTB) in advanced bladder and upper tract (UT) cancer patients.
Authors: Maia Manuel C. , Almeida Lorena , Dizman Nazli , Bergerot Paulo Gustavo , Lanman Richard B. , Banks Kimberly , Vogelzang Nicholas J. 
Published: February 2018

485 Background: In a series of 217 patients (pts) with advanced bladder cancer, ctDNA was detected in 89% (Grivas P et al ASCO GU 2017). We hav e previously reported an association between ctDNA detection and rTB in metastatic renal cell carcinoma (Maia et al ASCO 2017); it is unknown whether the same correlation exists in advanced bladder/UT cancers. Methods: Data was obtained from pts with advanced bladder or UT cancer from a single institution. Pts received ctDNA profiling as part of routine clinical care using a CLIA-certified platform assessing a panel of up to 73 genes. Clinicopathologic and radiographic data was obtained, including histology, Bajorin risk criteria and sum of longest diameter (SLD - a surrogate for rTB) from most proximal scan to ctDNA test. Results: A total of 36 pts (27:9 M:F) with a median age of 68 (range, 43-99) were assessed, with a total of 59 ctDNA tests. 3 tests were excluded due to lack of associated radiographic data. Primary site was bladder and UT for 26 and 10 pts, respectively. In total, 31 pts had metastatic disease and 5 pts locally advanced disease. Metastatic pts were characterized as having good and intermediate Bajorin risk in 15 and 16 cases, respectively (no poor risk pts were identified). Most proximal therapy to ctDNA test was cytotoxic chemotherapy in 19 cases, immunotherapy in 10 cases and a combination in 2 cases, while 5 pts did not receive any systemic treatment. Median number of genomic alterations (GAs) was 3 (range, 0-18). A significant association between ctDNA detection and SLD was found (p = 0.029). Furthermore, a correlation between cumulative mutant allele fraction and SLD was detected (R2 = 0.39; p = 0.003). The most frequent GAs in the cohort were in TP53, MET and KRAS, occurring in 10%, 5.6% and 5.6% of the cases, respectively. Serially collected ctDNA assessments and corresponding rTB data will be presented at the meeting. Conclusions: Detection of ctDNA was significantly associated with rTB, and a positive correlation between rTB and cumulative mutant allele fraction was also observed. Given the modest sample size, we are confirming these findings in larger validation series.
Long-term outcomes of intensity-modulated radiation therapy combined with neoadjuvant hormonal therapy for Japanese patients with non-metastatic prostate cancer.
Authors: Aizawa Rihito , Takayama Kenji , Nakamura Kiyonao , Inoue Takahiro , Kobayashi Takashi , Akamatsu Shusuke , Yamasaki Toshinari , Ogawa Osamu , Mizowaki Takashi 
Published: February 2018

49 Background: This study aimed to evaluate long-term outcomes of intensity-modulated radiation therapy (IMRT) combined with neoadjuvant (NA) hormonal therapy (HT) in Japanese patients with non-metastatic prostate cancer (NMPC). Methods: We retrospectively analyzed the data of 485 patients with T1-T4N0M0 adenocarcinoma of the prostate treated with IMRT combined with NA-HT. Of these patients, 32, 113, 250, and 90 patients were categorized into the low-, intermediate-, high-, and very high-risk groups, respectively, according to the NCCN risk classification. NA-HT was administered over a median duration of 6 months. In principle, 74 or 78 Gy in 2 Gy per-fraction were delivered to the prostate and seminal vesicles according to the risk. We did not administer adjuvant HT (A-HT) for any patient following the completion of IMRT. Salvage HT (S-HT) commenced when prostate-specific antigen (PSA) values exceeded 4 ng/mL. Results: The median follow-up period was 103.4 months, and the median PSA value at the initiation of S-HT was 5.1 ng/mL. In the low-risk group, the 8-year biochemical relapse-free survival, prostate cancer-specific survival, overall survival, and S-HT-free (SHTF) rates were 89.7%, 100.0%, 100.0%, and 96.7%, respectively. Those were 83.7%, 100.0%, 96.0%, and 94.3% for the intermediate-risk group, 64.5%, 97.8%, 87.0%, and 79.4% for the high-risk group, and 47.7%, 96.6%, 89.7%, and 53.3% for the very high-risk group, respectively. The estimated 8-year cumulative incidence rates of late gastrointestinal and genitourinary (grades 2–3) toxicity were 7.2% and 21.8%, respectively. We observed no grade 4 or higher toxicity. Conclusions: High-dose IMRT, combined with NA-HT and without A-HT under the early S-HT policy, achieved excellent survival outcomes with acceptable morbidities for a Japanese cohort with NMPC. Moreover, especially for high, and very high-risk patients, this approach could be a viable alternative to the uniform provision of long-term A-HT because more than the half of the patients maintained SHTF status over a period of 8-year after IMRT. Prospective trials are warranted to validate the findings of this study.
Discordance rate of PD-L1 expression between primary and metastatic lesions in urothelial carcinoma (UC).
Authors: Burgess Earle Frederick , Naso Caroline , Doherty Shannon , Guerrieri Renato , Livasy Chad , Hartman Aaron , Robinson Myra M. , Symanowski James Thomas , Grigg Claud , Graham David L. , Osei-Boateng Kwabena , Riggs Stephen Boyd , Clark Peter , Raghavan Derek 
Published: February 2018

493 Background: Immune checkpoint inhibitors (ICI) targeting PD-1 or PD-L1 are effective in select patients with advanced UC. High PD-L1 expression enriches for response to ICIs; however, the predictive value of PD-L1 expression is limited, which may be due in part to dynamic expression of PD-L1 in the tumor environment. We sought to characterize PD-L1 expression in primary UC and paired metastatic lesions to gain insight into the potential temporal discordance of tumor PD-L1 expression during the metastatic process. Methods: Immunohistochemical (IHC) staining for PD-L1 using the SP-142 antibody was performed on primary tumors and matched metastatic specimens in 83 patients with advanced UC. IHC staining was scored for the percentage of cells positive ( < 5%, ≥5%) in tumor cell (TC) and immune cell (IC) compartments. Correlation of PD-L1 expression in TCs and ICs was estimated using Spearman’s correlation coefficients (ρ). Cohen’s kappa statistics (κ) were utilized to assess the agreement in PD-L1 expression between groups. Results: High (≥5%) PD-L1 expression in primary and metastatic biopsies, respectively, was observed in 6.1% and 14.6% of TCs and in 7.8% and 11.7% of ICs. High co-expression of PD-L1 in both TC and IC compartments was infrequent in primary and metastatic lesions (3.6% and 2.6%, respectively). PD-L1 expression in TCs was positively correlated with PD-L1 expression in ICs in primary tumors (ρ = 0.47) and in metastatic lesions (ρ = 0.27). TC PD-L1 expression in primary tumors was correlated with TC PD-L1 expression in paired metastatic lesions (ρ = 0.44) but there was minimal agreement in high expression rates between primary and metastatic lesions in the TC compartment (κ = 0.147). IC PD-L1 expression in primary tumors was not correlated with IC PD-L1 expression in paired metastatic lesions (ρ = 0.05) and there was poor agreement in high expression rates between primary and metastatic lesions in the IC compartment (κ = 0.086). Conclusions: High PD-L1 IC expression is temporally discordant between primary and metastatic UC lesions. Future studies of PD-1/PD-L1 targeted therapies in patients with metastatic UC should utilize recent biopsies of metastatic lesions to define PD-L1 expression when feasible.
Comparative effectiveness of non-cisplatin (cis)-based first-line (1L) regimens in patients with metastatic urothelial carcinoma (mUC): Veterans Affairs control cohorts vs. IMvigor210.
Authors: Vander Velde Nancy S. , Guerin Annie , Ionescu-Ittu Raluca , Shi Sherry , Wu Eric , Lin Shih-Wen , Hsu Ling-I , Saum Kai-Uwe , De Ducla Sabine , Wang Jingjing , Li Shi , Derleth Christina Louise , Liu Shuqian , Shi Lizheng , Leppert John 
Published: February 2018

496 Background: For mUC patients (pts) ineligible for cis, 1L carboplatin (carbo)-based regimens and checkpoint inhibitors are recommended, but comparative data are lacking. We assessed OS in pts given 1L atezolizumab (atezo; anti–PD-L1) from Ph 2 study IMvigor210 and Veterans Affairs (VA) mUC pts treated with carbo standards. Methods: Carbo-based control cohorts were derived from the VA Health Care Network databases (diagnosed 2006-2017), with treatment (tx) defined per NCCN guidelines V2.2005. IMvigor210 eligibility criteria were used to refine non-cis VA cohorts. Prespecified OS predictors were balanced between VA and IMvigor210 pts using entropy (e)-balance weighting. OS was evaluated by Kaplan-Meier (KM) and Cox regression (weighted). Sensitivity analyses used stabilized inverse probability weighting (sIPW) and statistical adjustments. Results: Of 2056 VA pts included, 926 received carbo-based tx, of whom 380 received carbo+gemcitabine [CarboGem]; after IMvigor210 exclusion criteria, the carbo-based cohort included 282 pts, of whom 120 had CarboGem. Non-proportional hazards were seen with KM curves crossing at ≈ 5 (CarboGem) and 9 mo (carbo based). OS data are in the table. Weighted analyses showed OS benefit for atezo vs CarboGem and delayed benefit vs carbo-based tx. HRs from sensitivity analyses were consistent in direction and significance. Conclusions: We compared OS in mUC pts receiving 1L non-cis regimens in VA (carbo) and IMvigor210 (atezo) mUC cohorts. A lower risk of death was seen for atezo vs carbo, manifesting after a few months of tx. Randomized studies may validate these 1L mUC tx trends. Clinical trial information: NCT02951767. [Table: see text]
Vascular and tumor cell expression of VEGFR2 and molecular subtyping: An innovative biomarker approach in bladder cancer.
Authors: Nasir Aejaz , Falcon Beverly L , Wang Dan , Holzer Timothy R. , Nonte Elizabeth M , Chen Mia Yang , Fulford Angie D , Carter Julia H , Douglass Larry E , Pytowski Bronislaw , Bell-McGuinn Katherine M , Walgren Richard A. , Schade Andrew E , Chaudhry Aafia 
Published: February 2018

497 Background: Treatment approaches combining anti-angiogenic therapy with chemotherapy have shown promising clinical results in metastatic bladder cancer (BC). In order to interrogate the potential clinico-pathologic and molecular basis of these findings, we evaluated VEGFR2, vascular density and molecular subtyping in a series of BC patients. Methods: A custom-TMA with primary BC tissues from 117 patients (mean age 71 yrs; range 38-99 yrs; M:F = 83:34) treated at a single institution, was stained and scored (0-3) for CD34 (vascular density) and for VEGFR2 on tumor vessels and cells. CK5/6 and GATA3 IHC was scored by a pathologist to identify main molecular classes of BC. The association between clinico-pathologic variables, VEGFR2, CD34 and molecular subtypes was analyzed by Fisher’s exact test and ANOVA. Univariate and multivariate Cox proportional models were used for survival analysis. Results: Of 112 analyzable BC tissues, 41% were muscle-invasive (MIBC) vs. 56% non-muscle invasive (NMIBC) and 3% undetermined. Compared to NMIBC patients those with MIBC had shorter overall survival (p < 0.001). The main molecular subtypes included basal (11%), mixed baso-luminal (28%) and luminal (61%). Compared to luminal and baso-luminal subtypes, the majority of basal BCs were muscle invasive (p = 0.036). VEGFR2 expression was higher in tumor vessels but variable in tumor cells. 74% of BCs showed high-medium levels of VEGFR2 (scores 3-2) in tumor vessels and 88% had high-medium levels of tumor vascular density. Within basal, luminal and baso-luminal subtypes, 58%, 78% and 71% had high-medium levels of vascular VEGFR2 (p = 0.52), while 83%, 91% and 82% had high-medium levels of tumor vascular density (p = 0.08). Survival analyses showed increasing patient age, higher stage and lower VEGFR2 levels as independent predictors of shorter survival. Conclusions: Given the observed complexity of BC regarding VEGFR2 expression and vascular density across molecular subtypes, further investigation is warranted to understand how the frequent expression of VEGFR2 on tumor vasculature and variable expression in tumor cells relates to the efficacy of anti-angiogenic agents across these subtypes in bladder cancer.
Defining the DNA damage repair (DDR) genomic landscape of urothelial carcinoma of the bladder (UCB).
Authors: Dason Shawn , McPherson Victor , Teo Min Yuen , Isharwal Sumit , Audenet François , Bagrodia Aditya , Cha Eugene K. , Berger Michael F. , Zehir Ahmet , Schultz Nikolaus , Bajorin Dean F. , Rosenberg Jonathan E. , Al-Ahmadie Hikmat , Bochner Bernard H. , Pietzak Eugene J. , Solit David B. , Iyer Gopa 
Published: February 2018

502 Background: Impaired DDR is associated with response to platinum-based chemotherapy. Several genomically directed trials have been proposed using DDR alteration status for enrolment. In this study, we characterized the deleterious DDR alteration (DDRa) landscape of UCB across various clinical states. Methods: Targeted exon capture and sequencing of at least 341 cancer-associated genes was performed prospectively on 451 UCB specimens (MSK-IMPACT assay). We assessed sequencing data for deleterious alterations in 34 genes representing canonical DDR pathways. Deleterious alterations included truncating mutations, homozygous deletions, and functionally validated missense mutations. Results: Table 1. In NMIBC, deleterious DDRa were enriched in high-grade disease ([39/136, 28.7%] high grade vs. low-grade [2/28, 7.1%]; p=0.02). The frequency of deleterious DDRa in chemo-naïve MIBC was enriched relative to unmatched post-neoadjuvant chemotherapy (NAC) residual MIBC ([33/112, 29.5%] vs. [8/55, 14.5%]; p=0.01). Patients with metastatic disease had similar rates of deleterious DDRa to MIBC ([31/116, 26.7%] vs. [33/112, 29.5%]). The percentage of patients having any type of DDR alteration was similar across states. The proportion of patients with a deleterious DDRa relative to any DDRa was 41/77 (53.2%) in NMIBC, 33/65 (50.8%) in chemo-naïve MIBC, 8/27(29.6%) in post-NAC residual MIBC, and 31/68 (45.6%) in metastatic disease. Conclusions: DDRa are found across the UCB disease spectrum. ERCC2 and ATM are the most common DDRa although alterations were seen in most other DDR genes. Many alterations are of unknown significance and further characterization is needed to develop genomically directed treatment. [Table: see text]
Self-reported burden in patients with localized prostate cancer treated with stereotactic body radiation therapy (SBRT).
Authors: Pepin Abigail , Aghdam Nima , Johnson Colin , Danner Malika , Ayoob Marilyn , Yung Thomas M. , Lei Siyuan , Collins Brian Timothy , Dritschilo Anatoly , Suy Simeng , Lynch John , Collins Sean P. 
Published: February 2018

51 Background: Retaining quality of life in patients treated with SBRT for prostate cancer remains paramount. As such, balancing the benefits of treatment against the effects of therapy on patients is essential. The quality of life is influenced by the disease and treatment related burden. The EORTC QLQ-ELD14 (ELD14) is a validated questionnaire that can assess burden. This study reports burden trends in patients with prostate cancer treated with SBRT. Methods: All patients with localized prostate cancer treated with SBRT at Georgetown University Hospital from 2007 to 2016 were eligible for inclusion in this cross-sectional cohort. The ELD14 questionnaire was used to assess self-reported patient quality of life at time points before and following treatment. Initially, 267 patients (Median age of 70) responded to the ELD14 questionnaire. Approximately 30% received ADT. The specific questions reviewed for this study were focused on burden of disease and treatment. The responses to these questions were grouped into three clinically relevant categories (not at all, a little and quite a bit to very much). Results: Number of patients reporting quite a bit or very much burden from prostate cancer declined over time from 13% prior to treatment to 8% at 36 months post-SBRT. This was highest at one month post-SBRT (15%) and resolved to baseline by 6 months. Treatment burden similarly decreased over time from 10% to 3%. Patients treated with androgen deprivation therapy (ADT) experienced greater burden than others. At initial consult, 19% of patients on ADT reported quite a bit or very much burden from their illness. At one month post-SBRT, this had increased to 27% and subsequently decreased to 16% at 36 months. Of those not receiving ADT, 12% reported having quite a bit or very much burden from illness initially, 9% at one month and 6% at 36 months. Conclusions: This cross-sectional study suggests that the burden of clinically localized prostate and its treatment with SBRT improves over time. Increased burden was noted in patients receiving ADT. These findings can inform decision making in improving quality of life for patients with prostate cancer treated with SBRT.
Costs and of treating Gleason score 9 and 10 prostate cancer vary widely based on need for adjuvant therapy: A critical assessment into the long-term cost implications of additional treatment modalities.
Authors: Laviana Aaron Alan , Saigal Christopher , Resnick Matthew J. , Reiter Robert Evan , King Christopher R. , Demanes David Jeffrey , Steinberg Michael L. , Horwitz Eric M. , Kishan Amar Upadhyaya 
Published: February 2018

53 Background: The costs of treating localized, Gleason score 9 and 10 prostate cancer remain poorly described, especially when the particularly aggressive nature of the disease often requires a multimodal approach. We report the results of time-driven activity-based costing to assess the long-term costs of treating this subset of patients with either RALP, high-dose EBRT, or EBRT with a high-dose rate brachytherapy (BT) boost. Methods: Based on a multi-institutional cohort of 487 patients with Gleason score 9-10 prostate cancer, we generated process maps for each phase of care from the initial urologic visit through a median follow-up of 3.76 years, incorporating all prostate cancer treatment over this horizon. Costs were calculated per unit time, and the proportion of capacity for each step was determined. TDABC was defined as the sum of its resources. Results: Substantial cost variation was demonstrated between treatment modalities with an estimated median cost of $49,681 for EBRT, $35,140 for RALP, and $31,647 for EBRT + BT at 3.76 years. The primary driver in cost variation was the use of ADT. RALP (170 pts) ranged from $18,896 (29.5%) for no postoperative therapy to $63,270 for immediate long-term ADT (5.3%). EBRT (230 pts) had the greatest cost variation [Table 1]. Finally, EBRT + BT (336 pts) ranged from $26,522 for EBRT + BT alone (12.6%) to $37,834 for EBRT + BT + salvage ADT + HIFU (1.2%). Conclusions: Characterizing the costs associated with the distribution of treatments for men with high-risk prostate cancer is essential as we move towards health care accountability. There is substantial long-term cost variation between treatments in this subset of patients, and understanding these differences may affect treatment implications as we shift toward accountable payment models.[Table: see text]
Sentinel node biopsy in clinical stage I testicular cancer.
Authors: Blok Joost Marijn , Meijer Richard Paul , Kerst Jan M. , Vegt Erik , Bosch Ruud , Bex Axel , Van Der Poel Henk , Horenblas Simon 
Published: February 2018

550 Background: Approximately 20 – 30% of patients with testicular germ cell tumors (TGCTs) in clinical stage I (CS I) have occult metastatic disease at the time of presentation and will relapse under surveillance. The availability of a sentinel node procedure would enable early identification of patients with occult metastases. We report the long-term results of the sentinel node approach in CS I testicular tumor patients in our facility. Methods: Between 2001 and 2015, patients suspected of CS I TGCT in our third echelon referral center were asked to participate. SNs were identified using SPECT/CT and/or lymphoscintigraphy. Participants underwent laparoscopic retroperitoneal SN excision together with inguinal orchiectomy. Patients with a SN positive for occult metastases were treated with adjuvant chemotherapy. Follow-up was according to then current guidelines and consisted of clinical examination, tumor markers, abdominal/thoracic CT-scanning and chest X-rays. Results: Twenty-seven patients were included. In two patients, no sentinel nodes were visualized on scintigraphy. In twenty-five patients, a median of 3 SNs (range 1 – 4) per patient were removed. Two patients showed no malignancy on histopathologic examination of the testis. Of the 23 patients diagnosed with TGCT, three (13.0%) had occult metastatic disease. All 23 patients were without evidence of disease at a median follow-up of 62.2 months (range 22.3 – 143.4). Conclusions: The SN procedure enables early identification of patients with occult metastatic disease in CS I TGCT. Clinical trial information: M00LMT.
Comparative genomic profiling (CGP) of refractory/metastatic penile (mPSCC) and non-penile cutaneous squamous cell carcinoma (mCSCC).
Authors: Jacob Joseph M , Shapiro Oleg , Ferry Elizabeth Kate , Gay Laurie M. , Elvin Julia Andrea , Vergilio Jo-Anne , Suh James , Ramkissoon Shakti , Ali Siraj Mahamed , Schrock Alexa Betzig , Chung Jon , Miller Vincent A. , Stephens Philip J. , Bratslavsky Gennady , Ross Jeffrey S. 
Published: February 2018

552 Background: mPSCC is an aggressive malignancy with limited treatment options. Using CGP, we compared the therapy impacting genomic alterations (GA) between mPSCC and cutaneous mCSCC. Methods: DNA was extracted from 40 microns of FFPE samples from 78 cases of mPSCC and 338mCSCC.Comprehensive genomic profiling (CGP) was performed using a hybrid-capture, adaptor ligation based next generation sequencing assayto a mean coverage depth of > 500X. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: mPSCC patients were younger than mCSCC (Table). Both tumors types feature high CDKN2A, TERT and FAT1 GA frequencies. NOTCH1 and PTCH1 GA are also more common in mCSCC than mPSCC. CD274 ( PD-L1) amplification was rare in both tumor types. Targeted therapy opportunities in mPSCC included alterations in kinase pathways ( EGFR GA in 6%; FGFR3 and ERBB2 GA in 4%); MTOR pathway ( NF1 GA in 7% and PTENGA in4%) and DNA repair pathway ( BRCA2and ATMGA in 7%). TMB was significantly higher in the UV light exposed mSCC than mPSCC with both tumor types having potential for responsiveness to immunotherapies. MSI-High status was extremely rare for both mPSCC and mCSCC. HPV viral DNA was identified in 29% on mPSCC but only in 5% of mCSCC. TP53 GA were significantly more frequent in HPV- than HPV+ mPSCC and mCSCC respectively (P < 0.0001 for both). Clinical outcomes of selected patients will be presented. Conclusions: mPSCC is a unique subtype of SCC with distinctive genomic features that contrast with those identified in mCSCC of non-penile UV light exposed skin. Given the potential opportunities for targeted therapies and immunotherapies that can be uncovered, continued study of CGP for the guidance of treatment for patients with mPSCC appears warranted.[Table: see text]