bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of planning target volume for esophageal cancer target delineation with different ways.
Authors: Shao Qian 
Published: March 2020

e14735 Background: To compare the planning target volume (PTV) of esophageal cancer target delineation with different ways. Methods: There were 15 patients with middle chest esophageal cancer, involving 12 males and 3 females and aged 45-72 years. The median age was 59 years. Positioning in the CT slice thickness of 3mm on the outline of esophageal lesions as GTV.The CTV0 was created by manually contouring the esophagus for 30mm superiorly and inferior to GTV then adding 5mm circumferentially to the created volume to account for microscopic spread. For the PTV0, a 10mm margin in all direction was added to CTV0. The CTV6 was created by manually contouring the esophagus for 24mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV6, a 16mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV6. The CTV15 was created by manually contouring the esophagus for 15mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV15, a 25mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV15.The CTV30 was created by manually contouring the esophagus for 0mm superiorly and inferior to GTV then adding 5mm For circumferentially. The PTV30, a 40mm margin in superiorly and inferiorall direction and a 10mm margin in other direction was added to CTV15. Paired t-test using SPSS17.0 to p <0.05 was considered significant difference, compared PTV30, PTV15, PTV6, PTV0 volume. Results: The volumes of PTV30, PTV15, PTV6 and PTV0 showing with the mean ± standard deviation, were 392.51 ± 123.32cm3, 366.07 ± 112.78cm3, 346.55 ± 103.70cm3 and 342.36 ± 108.65cm3, respectively. The results were significant differences (p ≤ 0.001) except PTV6 vs PTV0. Conclusions: Different ways of esophageal cancer target delineation make significant effects on the PTVs. Choosing the delineation ways of CTV6 or CTV0 are better. It may benefit patients.
Analysis of tolerability of intravesical bacillus Calmette-Guérin (BCG) therapy in non-muscle-invasive bladder cancer.
Authors: Miyazaki Jun , Ishizuka Naoki , Hinotsu Shiro , Akaza Hideyuki , Nishiyama Hiroyuki 
Published: March 2020

e15004 Background: Although the effectiveness of BCG intravesical instillation with maintenance therapy (MT) has been shown (Hinotsu S. BJUI 2010), the treatment was not well tolerated. We aimed to characterize adverse events (AEs) affecting tolerability and to study the possible prediction of MT tolerability during the induction therapy (IT) by using data from the previous phase III trial. Methods: Forty-two patients received 81 mg intravesical BCG once weekly for 6 weeks as IT followed by thrice weekly instillations at 3, 6, 12 and 18 months as MT. AEs after each instillation were analyzed. The hazard ratio (HR) and 95% confidence intervals (CI) between the risk of each AE during IT and MT were analyzed by Cox regression. To assess the time between the randomization and the onset of each AE, HR and CI for patients without an AE were measured against those who developed the AE once, using the Wei-Lin-Weissfeld (WLW) Model. The WLW Model allows the analysis of recurrent AEs by controlling within-patient correlations in a marginal Cox model. Results: Fourteen of the 42 patients completed MT, of whom 11 completed as scheduled, and 3 completed with some modifications. For 28 who did not complete, 6 were withdrawn during IT and 22 during MT (of whom 15 had some MT modifications). Among 17 patients who experienced Grade (Gr) 3 AEs, 4 completed the treatment. In total there were 65 Gr3 events. Urinary frequency was most frequent event causing treatment cessation (7/38 events) and hematuria was the most common cause of treatment modification (7/13). The risk of an AE that occurred during IT recurring during MT was high for malaise (HR:3.49), pyrexia (3.33), and difficulty in urination (2.90). The WLW analysis revealed that malaise was relapsed in 18/21 patients (HR:5.81, CI:2.94-11.50, p<0.0001), difficulty in urination in 13/21 (4.56, 1.92-10.84, 0.0006), pyrexia in 14/18 (4.27, 2.18-8.37, <0.0001), hematuria in 36/39 (2.69, 1.79-4.04, <0.0001) and urinary frequency in 35/39 (2.30, 1.38-3.84, 0.0014). Conclusions: Gr3 urinary frequency was the most common cause of treatment cessation. The risk of the recurrent AE during MT will increase in those who develop AEs such as malaise, pyrexia, and difficulty in urination at IT.
Brain metastases in patients with urothelial carcinoma.
Authors: Boyle Helen Jane , Lavergne Emile , Droz Jean Pierre , Bonnin Nathalie , Flechon Aude 
Published: March 2020

e15009 Background: Muscle invasive urothelial cancers are infrequent. Patients (pts) with metastatic disease have poor prognosis. Brain metastases (BM) are rare. The aim of this retrospective study is to analyse the characteristics, the treatment and the evolution of patients with BM treated in a single centre. Methods: Thirty pts with BM were identified among the 1591 pts with urothelial carcinoma seen at the Centre Léon Bérard, between 1994 and 2011. The study population was described, overall survival (OS) from diagnosis of BM was estimated by Kaplan-Meier method and prognostic factors were explored using a Cox model. Results: Twenty seven pts in our series were male. Median age at initial diagnosis was 60 years (range: 33.9-78.9 years). Twenty two pts had primary bladder tumours and 8 upper urinary tract tumours. Twenty four pts underwent surgery for their primary lesion, 2 received chemoradiotherapy and 4 did not receive any radical local treatment. Six pts had metastatic disease at initial presentation: 3 were operated on. Median delay between initial diagnosis and BM was 16.6 months (range: 0-56.4 months), 3 patients had BM at initial presentation. Median time between first metastases and BM was 10 months (range=0-52 months). Eleven patients developed BM as one of the first sites of metastases. BM were symptomatic in 28 pts: specific neurological symptoms (n=25), headaches (n=6), epilepsy (n=2). For the 2 other pts, they were discovered on a systematic brain MRI. Eighteen pts had cerebral metastases only, 5 pts had cerebellar metastases only, 6 had both; the last patient had cerebral, cerebellar and meningeal involvement. Half of the pts had only 1 brain lesion. Five pts were operated on: 4 received postoperative radiotherapy; 19 patients were given radiotherapy alone and 6 did not get any local therapy. In this series, median OS from diagnosis of BM was 3.4 months (IC95% [2.2-10.3]). Only the administration of chemotherapy after the diagnosis of BM was significantly associated with OS; probably because only fit enough patients were offered treatment. Conclusions: Prognosis of patients with urothelial carcinoma and BM is poor; however some patients have long survivals. Treatment is not codified as there is little data in the literature.
Role of MCM as an adjuvant to urine cytology in the diagnosis of bladder cancer.
Authors: Narine Nadira , Thottakam Bensita M.V , Donnini Alessia , Dhanvijay Sushant , Saeb-Parsy Kasra , Wilson Alex , Rana Durgesh N 
Published: March 2020

e15011 Background: Urine cytology, a cheap non invasive first line test (PAP) has traditionally been used for the diagnosis of urothelial carcinoma (UC) as it has excellent sensitivity for the detection of high grade and in situ lesions. However, sensitivity for low grade carcinoma is rather varied as this is a problematic area with various mimics leading to both over and under diagnoses. To overcome this dilemma, a number of biomarkers and molecular tests have been employed with mixed results and varied financial implications. We report on a relatively cheap and easily adopted in vitro diagnostic test, Minichromosome maintenance (MCM) proteins, as an adjuvant to cytology in the diagnosis of both low and high grade bladder cancer (BC). MCM proteins play an important regulatory role in eukaryotic DNA replication and is expressed only as normal cells progress from G0 into G1/S phase of the cell cycle. However, over expression has been demonstrated in neoplasia in a range of sites including urothelium. Methods: 106 patients from gross haematuria (GH, 39) and cystoscopic surveillance (CS, 67) clinics were investigated for newly diagnosed and recurrent BC respectively by MCM and cytology with histological outcome being used as the gold standard. Results: Using biopsy positive outcome, MCM and cytology had a sensitivity of 91.7%, specificity of 86.6%, PPV of 66.7% and NPV of 97.3%. There was noticeably improved correlation of MCM and cytology with increasing grade of BC (Table). Conclusions: We showed the combination of MCM and cytology to be highly sensitive and specific for the determination of CIS, G2, and G3 BC with improved detection of G1 bladder cancer. The combination of MCM and cytology suggests that this offers promise as a novel diagnostic biomarker in GH and CS patients. [Table: see text]
Multidisciplinary management and use of neoadjuvant cisplatin combination chemotherapy in patients with muscle-invasive urothelial bladder cancer.
Authors: Hoffman-Censits Jean H. , Lin Jianqing , Lallas Costas D. , Showalter Timothy Norman , Den Robert Benjamin , Doubet Ellen , Brown Jillian , Singh Jaspreet , Dicker Adam , Gomella Leonard G. , Kelly William Kevin , Trabulsi Edouard John 
Published: March 2020

e15012 Background: Although randomized data support neoadjuvant cisplatin-based chemotherapy prior to cystectomy for muscle invasive bladder cancer (MIBC), a recent retrospective study of 14 academic centers demonstrated only 12% of patients eligible for cystectomy received neoadjuvant chemotherapy. We reviewed utilization of neoadjuvant chemotherapy in a cohort of patients with MIBC seen at the Genitourinary Multidisciplinary Cancer Clinic (GUMDCC) of the Kimmel Cancer Center at Thomas Jefferson University (TJU). Methods: With IRB approval, records were reviewed for patients seen in the GUMDCC by urologists, radiation and medical oncologists with MIBC expertise from August 2009 to August 2011. Results: Of the201 patients with bladder or urothelial carcinoma, 46 (23%) with T2-T4 MIBC were identified and evaluated for neoadjuvant chemotherapy prior to radical cystectomy. 14 of 46 (30%) had renal, cardiac or other comorbidities rendering them unfit for cisplatin or cystectomy, and 2 were never referred to medical oncology. Of the 30 patients eligible for cisplatin and cystectomy, 2 were treated at outside institutions, 4 were recommended for treatment but were lost to follow up, and 4 who had refused neoadjuvant chemotherapy had adverse pathology at cystectomy and received adjuvant chemotherapy. Twenty eligible patients (66%) initiated neoadjuvant chemotherapy at TJU, 8 of those (40%) on clinical trial. 100% of patients treated with neoadjuvant chemotherapy at TJU received cisplatin based regimens, and 17 of 20 patients received at least 3 cycles. Chemotherapy was initiated in an average of 29.8 days of multidisciplinary evaluation. Conclusions: Multidisciplinary evaluation and management of patients with MIBC leads to improved compliance with evidence based guidelines and higher rates of cisplatin based neoadjuvant chemotherapy administration compared with historic data.
Decision making in clinical stage I (CSI) testicular cancer (TC).
Authors: Palmieri Giovannella , Nappi Lucia , Condello Caterina , Formisano Luigi , Federico Piera , Rescigno Pasquale , Di Lorenzo Giuseppe , Matano Elide , De Placido Sabino , Damiano Vincenzo 
Published: March 2020

e15034 Background: Optimal management of CSI seminomatous (S) and nonseminomatous (NS) TC is an open question. Quality of life and patient preferences are the principal end-points for the best treatment choice. Multidisciplinary approach is required for CSI TC patients to allow an individualized treatment with a patient-centered approach and an active participation in decisions. The “shared decision making” (SDM) is the prevailing approach because patients together with clinicians arrive at a mutually agreed-on choice. We have a project concerning the involvement of patients with CSI TC in the SDM. Methods: We used some key points of SDM: define the problem; treatment options; discuss pros/cons; clarify patient preferences; clarify the patient’s understanding. Educational material are offered to patients. From 2005 to 2012, 32 patients with CSI TC were evaluated. For each patient some clinical and socio-demographic features, type of treatment chosen and some sequel related to treatment were analyzed. Results: Patients characteristics are reported in the table. 4 S patients chose surveillance, 10 chemotherapy and 6 radiotherapy. 2 NS patients chose surveillance, 9 chemotherapy. 4 relapsed: 1 S patient after 13 months from chemotherapy and 1 during the surveillance after 24 months. 2 NS patients relapsed after 12 and 18 months both during the surveillance. All relapsed patients received chemotherapy. Metabolic alterations were analyzed. 1 S patient treated with chemotherapy had a cardiovascular accident. Conclusions: We observed an high gap between surveillance and the active treatments: there is no best choice for every one so we should improve decision-making process and decision aids into the management of CSI patients with TC. [Table: see text]
Significance of zoledronic acid on survival in patients with bone metastases from renal cell carcinoma.
Authors: Fujii Yasuhisa , Yasuda Yosuke , Yuasa Takeshi , Sukegawa Gen , Kitsukawa Shinichi , Urakami Shinji , Yamamoto Shinya , Yonese Junji , Takahashi Shunji , Fukui Iwao 
Published: March 2020

e15038 Background: It remains unclear whether zoledronic acid (ZOL) improves overall survival (OS) for renal cell carcinoma (RCC) patients with bone metastases. We retrospectively investigated the clinical benefit of ZOL for OS in RCC patients with bone metastases. Methods: Between 1978 and 2010, 77 patients who had RCC metastatic to bone were treated in our hospital. Of them, 36 were treated with ZOL and their OS was significantly better than that of the other 41 patients (1- and 3-year survival, 84% and 73% versus 49% and 27%, respectively, p<0.001). OS rates were clearly discriminated according to MSKCC model stratification: 3-year survival rates in the favorable, intermediate and poor risk groups were 83% (n=12), 49% (n=45), and 19% (n=20), respectively (p=0.0033). To match characteristics in our retrospective study, we selected 45 patients conforming to MSKCC intermediate risk group criterion. In this cohort, 23 patients received ZOL (ZOL-treated group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint was OS and the secondary endpoint was the skeletal-related event (SRE) rate defined as the total number of SREs divided by the total years on study. Results: For the cohort of 45 patients, the median OS from diagnosis of bone metastases was 27.2 months. Multivariate analysis showed that low serum calcium (hazard ratio [HR]: 2.58, 95% confidence interval [CI]: 1.31 to 4.69; p=0.0083) and ZOL treatment (HR: 1.89, 95% CI: 1.27 to 2.96; p=0.0013) were independent factors predicting longer survival. The ZOL-treated group had significantly longer OS (1-year survival: 80.8%) than the non-ZOL-treated group (1-year survival: 59.1%, p=0.0034). A difference in OS between the two groups still was present (p=0.012) when the duration of molecular-targeted therapy was excluded from the OS period. Patients in the ZOL-treated group experienced a lower SRE rate (0.87/year) than patients in the non-ZOL-treated group (1.82/year, p=0.0453). In particular, none of the patients in the ZOL-treated group developed spinal compression whereas 6 (28%) in the non-ZOL-treated group did (p=0.0479). Conclusions: The current study indicates that ZOL not only reduces SREs but possibly improves OS in these patients.
Evaluation of parameters for treatment duration of sunitinib in metastatic renal cell carcinoma.
Authors: Kossoff Ellen , Batty Nicolas , Ceacareanu Alice C. , Attwood Kristopher , Miller Dustyn , Rabey Jonathan , Lee Charlene , Ahmad Ahmad , Ebos John M. , Schwaab Thomas , George Saby , Pili Roberto 
Published: March 2020

e15042 Background: In metastatic renal cell carcinoma (mRCC), there is a need for predictive indicators for treatment duration (TD) of sunitinib. Our study evaluates parameters that may be associated with TD of sunitinib. Methods: From 01/2007-12/2011, consecutive mRCC patients (pts) were reviewed. Responders (R) were defined as having either complete response (CR) or partial response (PR) by Response Evaluation Criteria In Solid Tumors (RECIST) criteria, while non-responders (NR) were defined as having either stable disease (SD) or progressive disease (PD). Long term duration (LTD) was defined as therapy with sunitinib ≥ 18 months (mos). Hazard ratios (HR) and 95% confidence interval (95CI) representing the association between TD and specific parameters were computed with Cox proportional hazard model. Results: After a median follow-up of 9.8 mos (<1 - 63.8) of 128 mRCC pts, 57 (45%) received sunitinib. Responses were CR, PR, SD, PD of 3, 13, 8 and 33 pts, respectively. LTD was observed in 9 pts (21%). Hemoglobin < 12.5 g/dL (p = 0.048), prior nephrectomy (PN) (p = 0.001), prior therapies (p = 0.016), dose reduction (DR) (p = 0.001), an increased skin toxicity (p = 0.025) and low/intermediate (LI) Memorial Sloan-Kettering Cancer Center (MSKCC) risk-groups (p = 0.003) were associated with longer TD and a higher ANC (p < 0.0001) with shorter TD. In the multivariate analysis, PN was the only significant prognostic factor [HR 0.3 (95CI 0.12 -0.72) p = 0.007] that was associated with prolonged TD. Pts with LTD had a lower baseline ANC (p= 0.037), a LI MSKCC (p = 0.026), higher frequency of DR (p = 0.007), increased skin (p = 0.017) and endocrine (p = 0.015) toxicities and an increase of body mass index (BMI) from baseline (p = 0.008). When adjusted for BMI and performance status, results were maintained. Progression free survival (PFS) and overall survival (OS) of pts with LTD were not reached. However, both PFS and OS of R with TD < 18 mos, were 19.5 mos 95CI (3.4 - 27.9). Conclusions: PN, lower baseline ANC, DR, an increase of BMI from baseline, skin and endocrine toxicities were associated with prolonged TD of sunitinib in mRCC. There is a need for prospective studies to develop a predictive TD model in this setting.
Comparative effectiveness of front-line agents in the treatment of metastatic clear cell renal cell carcinoma.
Authors: Haaland Benjamin , Chopra Akhil , Lopes Gilberto de Lima 
Published: March 2020

e15045 Background: Based on improved clinical outcomes in randomized controlled clinical trials (RCT) the FDA has approved 4 drugs in the front line treatment of good to intermediate risk metastatic clear cell renal cell carcinoma (RCC). However, there is little if any comparative data to help choose the most effective drug among these agents. Methods: We performed an indirect comparative effectiveness analysis of the pivotal RCTs (Escudier JCO 2009 and 2010, Rini JCO 2010, Motzer JCO 2009, Sternberg JCO 2010, MRCRCC Lancet 1999, Steineck Acta Oncologica 1990, Pyrhonen JCO 1999, Kriegmair Urology 1995) evaluating outcomes with sunitinib (SU), sorafenib (SO), bevacizumab plus interferon alpha (B+I), pazopanib (P), interferon alone (I) and other controls. Progression-free-survival (PFS) was the main endpoint. Other endpoints included response rate (RR) and overall survival (OS). Estimates, confidence intervals, and p-values from analyses that are stratified by risk factors were used throughout if available. A linear mixed effects model with a random effect for each study and known error variances was fit by restricted maximum likelihood and used to obtain indirect estimates. Results: The indirect estimate of the hazard ratio (95% confidence interval; p-value) for PFS for SU vs. B+I is 0.813 (0.624-1.059; p=0.125); for B+I vs. SO is 0.753 (0.497-1.141; p=0.181); for P vs. B+I is 0.963 (0.612-1.518; p=0.874); for SU vs. SO is 0.613 (0.392-0.956; p=0.0311); for SU vs. P is 0.844 (0.521-1.366; p=0.49; for P vs. SO is 0.726 (0.407-1.295; p=0.278)(Figure 1). SU, P, B+I had better PFS than I alone and than other controls, while SO did not. SU had statistically significantly better RR when compared to P, SO and B+I with HR of 0.254, 0.215 and 0.419 (all p<0.05). OS data was not available to compare all agents and may be confounded by cross-over in the trials. Conclusions: Based on PFS, SU, B+I and P are adequate front line options in the treatment of advanced clear cell RCC. As SU had better RR it may be a preferred option for patients with symptoms or large disease burden. SO should not be considered an optimal front line treatment.
CD98hc (SLC3A2), a novel biomarker correlating with grade of malignancy in renal cell cancer.
Authors: Pöttler Marina , Aaitel Andrea , Schmidinger Manuela , Zielinski Christoph , Prager Gerald 
Published: March 2020

e15083 Background: In a variety of malignant diseases certain malignant markers either predict treatment response towards systemic therapies or have a prognostic impact for cancer patients. While a variety of such actionable as well as treatable targets have been characterized, although only in certain cancers, in renal cell cancer (RCC) no prognostic markers have so far been identified. Thus, grading according to the S.A. Fuhrman grading system from 1982 is the only prognostic feature and currently widely considered for treatment assessment. Methods: Paraffin-embedded tumor tissue sections derived from clear cell RCCs were immuno-histochemically analyzed for expression of embryonic transmembrane antigen CD98hc (SLC3A2). Expression levels were semi-quantitative analyzed and results were correlated with grade of differentiation, using the widely accepted Fuhrman classification. Results: We found that grade of malignancy of ccRCCs were directly correlated with high CD98hc expression levels. Semi-quantivative analyses revealed that 0 % (0/2) of grade 1 ccRCC, 70.0 % of grade 2 ccRCC (14/20), 86.6 % of grade 3 (26/30) and 100 % of grade 4 (10/10) were CD98hc positive. (p < 0.01, Qui-Quadrat Pearson test, n = 62). In contrast, tumor stage as determined by the WHO TNM system did not correlate with CD98hc levels (p > 0.05). Conclusions: From these data, we conclude that CD98hc is expressed in RCCs, whereby the extent of expression is likely to correlate directly with grade of malignancy. In ccRCCs, CD98hc might represent a novel and reliable marker for more aggressive and less differentiated subtypes.