bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two sequential dose-dense regimens of CGP, followed by MVAC in patients with metastatic urothelial carcinoma (mUC): A single institution, explorative trial.
Authors: Donini Maddalena , Brighenti Matteo , Giganti Maria Olga , Panni Stefano , Perrucci Bruno , Pizzo Claudio , Gerevini Fabiana , Foramitti Marina , Marchi Gianluca , Potenzoni Michele , Prati Andrea , Quarta Matteo , Benecchi Luigi , del Boca Carlo , Passalacqua Rodolfo ,   MEDeA MEDicina e Arte, Onlus Cremona
Published: May 2019

e16023 Background: Currently, cisplatin, gemcitabine, paclitaxel (CGP) and MVAC are the most active chemotherapy regimens in mUC. We tested the hypothesis that two sequential non-cross-resistant, dose-dense (DD) regimens may target different cancer cells, avoid drug resistance, and improve response rate. Methods: This is a single institution, explorative trial. The aim is to evaluate the incremental benefit of the two regimens in terms of complete response and long term survival. We treat all consecutive, chemo-naïve mUC patients with 4 cycles of CGP dose-dense every 14 days followed by 4 cycles of MVAC every 14 days. In all cycles we used Pegfilgrastim 6 mg on day 3. Pts were evaluated with CT scan at the baseline, after 4 cycles, at the end of chemotherapy and then every 3 months for 2 years and 6 months thereafter. Results: From 2007 to 2018, 67 consecutive pts were included. Male were 82%; median age 66 years (33-83); Bajorin risk factors was 0 in 31%, 1 in 52%, 2 in 16%. The majority of pts were hospitalized for three days during chemotherapy and received hydration and supportive therapy. After the first 4 cycles of CGP, we observed 7% CR, 46% PR, 31% SD, and 12% PD. After the 4 sequential cycles of MVAC DD we observed a global 25% of CR, 33% PR, 10% SD, and 24% PD. Median TTP was 8.2 months (95% CI, 7.3-10.1) and median OS was 18 months (95% CI, 10.8-26.1). 5 pts are still alive after more than 30 months and maintaining complete response. Main grade 3–4 toxicity included anemia 27%, asthenia 23%, neutropenia 19% (febrile 7%), thrombocytopenia 13%. Conclusions: The sequential use of these two DD regimens is active and leads to an increased number of complete response and possible longer survival. A randomized trial is needed to confirm our results.
Does neutrophil to lymphocyte ratio correlate with toxicities and outcome of patients with genitourinary cancers treated with checkpoint inhibitors?
Authors: Maruzzo Marco , Pierantoni Francesco , Basso Umberto , Deppieri Filippo Maria , Dionese Michele , Lamberti Evelina , Gardiman Marina , Pizzirani Enrico , Gardi Mario , Porreca Angelo , Zattoni Filiberto , Zagonel Vittorina 
Published: May 2019

e16032 Background: Few data are available concerning the role of neutrophil and lymphocyte counts in predicting toxicities and outcome in patients (pts) with genitourinary cancer treated with recent immunotherapy. Methods: We retrospectively reviewed the clinical charts of all pts with metastatic renal cell (RCC) or urothelial cancer (UC) treated at our Institute with immunotherapy(Nivolumab with or without Ipilimumab, Atezolizumab, Durvalumab, Pembrolizumab), having at least one response assessment after starting treatment. Results: We identified 117 pts treated from May 2015 onwards, median age: 68 years (range 39-84), 72% males, 53% with UC. Incidence of G3/4 toxicities was 17%, while 23.9% of pts needed an high dose steroid treatment because of immune-related toxicities (IrT). Median PFS and OS were 7.0 and 24.1 months, respectively for RCC, and 2.8 and 7.1 months, respectively for UC. 56 pts had progressive disease at best response. Baseline value of neutrophils or lymphocytes does not correlate with IrT (t test, p = 0.399, p = 0.728, respectively). In the IrT events, no significant increase of lymphocytes was detected (p = 0.160). The incidence of a IrT which needed steroid treatment positively impact in PFS (p = 0.03) but not in OS (p = 0.74). The use of steroid therapy was not associated with a different outcome in terms of OS (p = 0.49 for UC and p = 0.18 for RCC) and associated with a better PFS in RCC (p = 0.018). Steroid use was associated with the probability of non-progressive disease at first assessment (Chi-squared test, p = 0.015). In our cohort, baseline neutrophil to lymphocyte ratio (NLR) ≥ 3 correlate with a shorter PFS and OS in UC (p = 0.026 and p = 0.003 respectively), while it does not in RCC (p = 0.104 and p = 0.678 respectively). In our cohort, baseline neutrophil to lymphocyte ratio (NLR) ≥ 3 correlate with a shorter PFS and OS in UC (p = 0.026 and p = 0.003 respectively), while it does not in RCC (p = 0.104 and p = 0.678 respectively). In UC, the positivization of NLR after 2 cycles predicts a shorter PFS for UC (p = 0.008) and a trend for OS. Conclusions: In our retrospective single-center experience, NLR confirms its role in UC even in a cohort treated with immunotherapy and its variation predicts shorter outcome, while neutrophils or lymphocytes do not relate with IrT. The use of steroid for IrT is safe since it does not impact on survival and is associated with a higher probability of non-progressive disease at first assessment.
Trend in the use of neo-adjuvant chemotherapy for the management of muscle invasive bladder cancer at a major tertiary care hospital in Pakistan.
Authors: Jabbar Adnan Abdul , Maqbool Muhammad Asad , Mirza Muhammad Bilal 
Published: May 2019

e16033 Background: Although the use of Neoadjuvant Chemotherapy (NAC) has now become the standard of care for Muscle Invasive Bladder Cancer (MIBC) in the world, most patients in lower- middle-income countries (LMIC), like Pakistan, are still undergoing upfront surgery despite being ideal candidates for chemotherapy. Multi-disciplinary tumor boards have been critical in the change of this trend in the developed world. We aimed to assess the trends in the use of NAC for patients with muscle invasive bladder cancer before undergoing definitive surgery. Methods: We included patients who underwent surgery for ≥ cT2 MIBC without distant metastasis between 2011 and 2015 at a tertiary care hospital in Karachi, Pakistan. We retrospectively assessed the trends in NAC compared to upfront surgery in these patients. Results: Among the 171 patients included in our study, only 4 (2.34%) received NAC, whereas the other 167 (97.67%) underwent upfront surgery without NAC. Out of the 90 patients who underwent surgery for MIBC between 2011 and 2013, none of them received NAC and underwent upfront surgery. Among the 81 patients with MIBC in 2014 and 2015, 4 patients received NAC before surgery whereas the other 77 underwent upfront surgery. Conclusions: The adoption of NAC for MIBC remains a challenge in lower- middle-income countries such as Pakistan. Introduction of a multidisciplinary tumor board in our hospital since 2014 has shown a slight change in this trend. Better communication between different departments remains the key in significantly changing the trend of a much desired standard of care.
Pretreatment eosinophil counts (PEC) in metastatic urothelial carcinoma (mUC) treated with anti-PD1/PD-L1 checkpoint inhibitors (CPI).
Authors: Mota Jose Mauricio , Teo Min Yuen , Whiting Karissa , Ostrovnaya Irina , Li Han , Lee Chung-Han , Funt Samuel Aaron , Callahan Margaret K. , Iyer Gopa , Bajorin Dean F. , Rosenberg Jonathan E. 
Published: May 2019

e16035 Background: Eosinophils may influence anti-tumor immunity, having been associated with outcomes in CPI-treated melanoma. We sought to examine the association between PEC and outcomes of CPI-treated mUC. Methods: Independent CPI-treated cohorts were identified: discovery (n = 60, Teo et al JCO 2018) and validation (n = 111, non-overlapping CPI-treated mUC patients [pts] from 2014-19). Uni- and multivariate analyses were performed using Cox proportional hazard models to evaluate prognostic value of PEC on (i) overall survival (OS) and (ii) time on treatment (ToT). A platinum-treated metastatic cohort (n = 81, Teo et al, CCR 2017) was used as non-CPI comparator. Results: The cohorts showed comparable OS and pts characteristics, except higher proportion of females and lower neutrophil at baseline (Neut) in the validation cohort. In the discovery cohort, PEC as a continuous variable showed a significant positive association with OS (HR 0.01, 95% CI 0.00-0.29, P = .009). PEC of 100 cells/µL was set as the optimal cut-off point (Eos-L: < 100 cells/µL, n = 9; Eos-H: ≥100 cells/µL, n = 51). Eos-L showed inferior outcomes (OS: HR 3.98, 95%CI 1.85-8.56, P < .001; ToT: HR 2.45, 95%CI 1.17-5.10, P = .017). Similar association was seen in the validation cohort (Eos-L, n = 17; Eos-H, n = 94; OS: HR 2.51, 95%CI 1.31-4.80, P = .006; ToT: HR 2.22, 95%CI 1.29 - 3.80, P = .004). A multivariate model adjusting for other prognostic variables was created (table). In the chemotherapy cohort, continuous Eos or Eos-L was not associated with OS/ToT, with or without adjusting for known prognostic factors (P > 0.5). Conclusions: The association between Eos-L and shorter OS in CPI- but not chemotherapy-treated cohorts might represent a potential negative predictive biomarker for CPI in mUC. [Table: see text]
Different expression and prognostic implications of PD-L1 in tumor cells and immune cells with the SP263 monoclonal antibody in Chinese urothelial carcinoma patients.
Authors: Zhong Qiaofeng , Zhou Ai-Ping , Shou Jianzhong , Ying Jianming , Shi Yuankai , Yu Yue , Ling Yun , Shen Zhirong , Zhang Yun 
Published: May 2019

e16040 Background: PD-L1 is expressed on tumor cells (TC) and tumor immune cell (IC) infiltrates. The aim of this study was to explore the expression and the clinical implications of PD-L1 in TC and IC with the SP263 monoclonal antibody and the correlation with clinicopathological features and survival prognosis in urothelial carcinoma(UC) patients. Methods: Formalin-fixed paraffin embedded tumor specimens were collected from 172 patients with UC who received nephroureterectomy or cystoscope biopsy in our center from 2009 to 2016. Tumor samples were evaluated for PD-L1 membrane expression by immunohistochemistry (IHC) using VENTANA PD-L1 (SP263) Assay performed on the automated BenchMark ULTRA platform. PD-L1 expression status was determined by PD-L1 membranous staining at any intensity on TC or IC.PD-L1 is defined as positive if either ≥25% TC or ≥25% IC express membranous PD-L1.Data was analyzed by SPSS software. Results: Among 162 patients, TC and IC infiltrate PD-L1 positivity were detected in 16 (9.9%) and 45 cases (27.8%), respectively. The PD-L1 positivity of TC in female (19.4%) was higher than that in male (7.1%), P = 0.029, and so was in the patients with lymph node metastasis (20.7%) than those without metastatic lymph node (7.5%) , P = 0.031.While these correlation were not observed with PD-L1 positivity in IC. PD-L1 positivity both in TC and IC were not related to age, smoking history, specimen type , tumor size , histology grade, pT, pN stage (P > 0.05) .With a median follow-up of 60.9 months, patients with positive PD-L1 expression in IC have more favorable DFS (NR vs 26.3 months, P = 0.032) and OS (NR vs 71.2 months, P = 0.001) than those with negative PD-L1 expression in IC. More significant differences in DFS (NR vs 18 months, P = 0.002) and OS (NR vs 29.8months,P < 0.001) were observed in patients with T2-4 and PD-L1 positive expression. However, We did not find a statistically correlation between PD-L1 positivity in TC and prognostic outcomes. Univariate and multivariate analyses revealed that patients with PD-L1 positive expression in TC had poorer DFS (HR = 2.573; 95% CI, 1.246–5.313;P = 0.011). Whereas positive PD-L1 expression in IC independently correlated with better OS (HR = 0.303; 95% CI, 0.137–0.671;P = 0.003). Conclusions: PD-L1 positivity in IC is higher than TC in urothelial tumor. Positive PD-L1 expression in IC is associated with better OS and DFS while no correlation between PD-L1 positivity in TC and outcome was observed.
Management of stage I seminomatous germ-cell cancer (SGCC): Results from 4 different risk-adapted strategies in a single institution.
Authors: Riudavets Mariona , Anguera Georgia , Camacho Daniela , Bujosa Aida , Terés Raul , Borrell Maria , Gallardo Pablo , Martin Berta , Molto Consolacion , del Carpio Luis , Martin Cristina , Sancho Gemma , Algaba Ferran , Palou Joan , Maroto Pablo 
Published: May 2019

e16047 Background: Management of stage I SGCC depends on pathological findings after orchiectomy. Four risk-adapted strategies were sequentially applied in a single institution during a 24-year (yr) period according to national guidelines. Here, we compare treatment burden and outcomes of each of them. Methods: From 1/1994 to 1/2018, 208 patients with stage I SGCC were prospectively included in 4 cohorts. Those without risk criteria underwent close surveillance. Patients received active treatment as follow: Group 1: 1994-1999, only patients with T > pT1 received 2 cycles of carboplatin (CBDCA AUC7 x2); Group 2: 1999-2003, patients received CBDCA AUC7 x2 if either tumor size > 4cm or rete testis invasion; Group 3 : 2004-2009, CBDCA AUC7 x2 if both tumor size > 4cm and rete testis invasion were present; Group 4 : ≥2010, CBDCA AUC7 x1 if either tumor size > 4cm or rete testis invasion. Kaplan Meier and log-rank tests were used to evaluate disease-free survival (DFS), Kruskal-Wallis test to compare amount of chemotherapy received per patient. Results: At a median follow-up of 108 months [range 3-423], 19 (9.1%) relapses had occurred. Global 3 and 5-yr DFS were 92.3% and 90%. All relapsing patients were rendered disease-free with 4 cycles of cisplatin (CDDP) - etoposide. Table 1 summarizes results by cohort: Conclusions: A risk-adapted program provided an overall specific survival of 100%. A clinically significant difference in RR was observed when 1 or 2 courses of CBDCA were given. In our series and considering treatment burden, vascular invasion was a better criteria for patient selection to adjuvant chemotherapy, showing a similar DFS but a lower no of total platinum cycles per patient.[Table: see text]
Site, age, and gender distribution of extra-gonadal germ cell tumors in the US from 1973 to 2015.
Authors: Pan Elizabeth , Ihenacho Ugonna , Cortesssis Victoria , Barakzai Syem , Hu James S 
Published: May 2019

e16051 Background: Germ cell tumors (GCT) commonly arise in post pubertal gonads where they are influenced by sexually dimorphic hormone signaling. More rarely, extra-gonadal GCTs (EGGCTs) arise in midline sites, coinciding with the route of primordial germ cell migration. EGGCTs are proposed to arise from cells not completing this migration. We characterized the incidence of EGGCTs according to patient and tumor features in an attempt to elucidate tumor origins. Methods: In Surveillance, Epidemiology, and End Results (SEER) Program SEER*Stat Database SEER 9 Regs Research Data, 1973-2015, primary EGGCT cases were identified by ICD-O-3 histologic types (seminoma: 9060-9062, 9064; non-seminoma 9065-9101) grouped into central nervous system (CNS), mediastinum, and other EGGCT sites. Age-specific incidences for males and females were divided into adolescents and young adults (AYA) defined by the National Cancer Institute as 15-39 years of age, and younger childhood and older adult groups. Results: In AYAs and older adults, age-adjusted incidence of males exceeded that of females at all sites (p≤0.006, all comparisons) (Table). Male incidence was highest in AYAs (all EGGCT, 4.35/1,000,000 person-years (Mpy); mediastinum, 2.17/Mpy; other 0.68/Mpy). Female incidence was highest in childhood (CNS, 0.86/Mpy; mediastinum, 0.14/Mpy; other 0.64/Mp-y). Conclusions: Patterns of EGGCT incidence differ substantially between sexes. Permissive extra-gonadal sites of males or male-predominant exposures may explain higher incidence in males. Alternatively, EGGCT precursor cells may have sex-specific features affecting malignant potential. [Table: see text]
Impact of cannabis (CA) use on chemotherapy (C) treatment and tumor characteristics of patients (pts) with testicular germ cell tumor (TGCT): Experience of the Centre Léon Bérard (CLB).
Authors: Arnaud-Coffin Patrick , Moriceau Guillaume , Lorcet Marianne , Couillet Audrey , Boyle Helen Jane , Flechon Aude 
Published: May 2019

e16054 Background: TGCT are the most frequent cancers in men aged 15-45. This population is increasingly exposed to CA that is illegal in France. Its consequences on treatment and prognosis remain unknown. Methods: The use and the quantity of CA were evaluated for all pts treated by C for a TGCT in the CLB from 01/2016 to 06/2018. Tobacco (T) and alcohol (A) co-addictions were also analyzed. All pts had before starting C pulmonary test with diffusing capacity of the lung for carbon monoxyde (DLCO) evaluation. We searched a link between the use of toxics, contraindication to Bleomycin (B) due to decreased DLCO and tumor characteristics: stage and IGCCCG prognostic groups. Results: One hundred and thirty two pts with a median age of 33.5 years (interval: 17-65) received C for TGCT mainly for NSGCT (n = 97, 73%). Nine pts (7%) were treated in the adjuvant setting (1: 6 or 2 BEP: 3). In metastatic pts, 79 (60%), 30 (23%) and 14 (10%) were considered as good, intermediate and poor prognosis (PG) according to IGCCCG respectively. BEP was given for 3 cycles to 63 pts and 4 to29 and 6 pts received a dose dense regimen according to GETUG13. Eleven pts didn’t received B (5: 4EP, 6: 4VIP) because of DLCO alteration before the beginning of C. Eleven pts treated with B switched to a regimen without B due to a decrease of the DLCO during treatment. CA use was frequent (n = 20, 15%) with 8 pts (6%) having a regular CA consumption (median 5 joints/d). Seventy eight pts (59%) were regular T smokers. Co-addictions for CA consumers were frequent (90% for T and 50% for A). T and CA smokers had more DLCO alteration leading to B contraindication (p = 0.01 and p = 0.04). A quarter (n = 5) of pts using CA didn’t received B, and only 1 pt who didn’t receive B was not a smoker (T and CA). The use of CA was associated with PG, OR 5.46 (CI 95%: 1.35-21.2; p = 008). We could not observe a relationship between relapse and the use of CA (p = 0.34) because of the small number of relapses (n = 8). Half (n = 10) of CA consumers were single men and 25% (n = 5) were unemployed. Conclusions: The use of CA is significantly associated with PG and with a reduction of B use due to adecreased DLCO. The impact of CA intoxication is negative on the quality of treatment (because of more contraindications to B). The association with PG remains unclear, but may be related to social isolation.
Outcome of patients with stage 2 or stage 3 seminoma treated with 3 cycles of cisplatin-etoposide chemotherapy (EP120): Updated data from a single center retrospective study.
Authors: Gardiner Claudia , Hutton Paul , Jafri Mariam , Porfiri Emilio 
Published: May 2019

e16061 Background: Metastatic seminoma is eminently treatable with platinum-based chemotherapy with either 3 cycles of BEP—bleomycin (B), etoposide (E) and cisplatin (P)—or 4 cycles of EP, achieving remission in more than 95% of the patients. However, bleomycin has a substantial toxicity profile and can cause life-threatening lung toxicity. Whether similar cure rates can be achieved without exposing patients to bleomycin is still undetermined. We describe our 19-year experience of treating patients with stage 2 or stage 3 seminoma with 3 cycles of EP chemotherapy. Methods: Patients who received 3 cycles of EP120 chemotherapy (50mg/m2 cisplatin day 1 and 2 and 120mg/m2 etoposide days 1, 2 and 3 every 3 weeks for 3 cycles) for stage 2 or stage 3 seminoma between 01/03/2000 and 31/05/2015 were identified. Data were retrospectively collected on stage, prognostic group, previous adjuvant treatment, serological and radiological response, time to relapse and subsequent management, progression-free survival (PFS) and overall survival (OS). Results: We identified 115 patients who received EP120 for seminoma and who met the inclusion criteria. Median age was 40 years (range 17-72). All patients were in the good-prognosis group. 103 patients (90%) were diagnosed with stage 2 seminoma, 12 patients (10%) with stage 3 (3 patients stage 3a and 9 stage 3b). 97 patients (84%) presented with stage 2 or 3 seminoma and 18 patients (16%) had progressed to stage 2 or 3 following adjuvant radiotherapy or adjuvant carboplatin chemotherapy for stage 1 disease. Seven patients (6%) with stage 2 seminoma relapsed after EP120 chemotherapy: 2 patients ≤3 months and 5 patients ≥ 3 months. None of the patients with stage 3 disease has relapsed so far. Of the 7 patients who relapsed, 2 received radiotherapy, 4 received TIP (paclitaxel, ifosfamide, cisplatin) chemotherapy and 1 received a combination of TIP chemotherapy and radiotherapy. All patients who relapsed after EP120 are currently in remission. Two of the 115 patients (1.7%) died whilst in remission and of unrelated causes. The 5-year PFS was 94% and the OS was 98%. Conclusions: Our data suggest that patients treated with 3 cycles of EP120 had survival rates similar to patients treated with more aggressive chemotherapy regimens.
Cost-effectiveness of pazopanib as first-line treatment of metastatic renal cell carcinoma from National Health Service United Kingdom perspective.
Authors: Ratto Barbara Elizabeth , Khare Ankur , Gudala Kapil , Gunda Praveen 
Published: May 2019

e16088 Background: Recently, several therapies have been approved for treatment of metastatic renal cell carcinoma (mRCC) in the United Kingdom (UK); however, there is scarcity of comparative evidence to assist treatment decisions. We evaluated the cost-effectiveness of pazopanib as first-line treatment of mRCC from a UK National Health Service perspective. Methods: A partitioned-survival analysis model with 3 health states (alive with no progression, alive with progression, or dead) was used to evaluate the cost-effectiveness of pazopanib compared to sunitinib, tivozanib and cabozantinib in treatment-naive mRCC patients with treatment cycle length of 1 week and time horizon of 10 years. The model was populated with clinical effectiveness data obtained from network meta-analysis of pivotal trials and data on costs and utilities collected from UK-specific resources. The key model outcomes were quality-adjusted life years (QALY) and incremental cost-effectiveness ratio (ICER). Probabilistic and one-way sensitivity analyses were performed to test the uncertainty regarding model results. Results: Base-case analysis found that pazopanib was dominant (i.e. less costly and more effective) compared to sunitinib and tivozanib. Pazopanib had lower total costs (£69,861 vs £71,398 and £73,530) and higher QALYs (1.901 vs 1.835 and 1.669, respectively) compared to sunitinib and tivozanib. When compared with cabozantinib, pazopanib was found to be less costly (£174,735 vs £69,861) and less effective (total QALYs, 2.213 vs 1.901, respectively). Results of the probabilistic sensitivity analysis showed that at a willingness-to-pay (WTP) threshold of £30,000 per QALY, the probability of pazopanib being cost-effective was highest as compared to all comparators (84% vs sunitinib, 98% vs tivozanib and 100% vs cabozantinib). One-way sensitivity analysis revealed that effectiveness inputs, time horizon and others are model influencers. Conclusions: Based on a WTP threshold of £30,000/QALY gained, pazopanib is the most cost-effective treatment option compared to sunitinib, tivozanib and cabozantinib, for mRCC patients in UK.