bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical features of extragonadal germ cell tumors: A SEER analysis.
Authors: Alnimer Yanal Mufeed , Katato Khalil 
Published: May 2019

e16064 Background: Extragonadal germ cell tumor is an uncommon type of malignancy. We aim to identify the clinical features and the prognosis in various histological subtypes in these patients using the Surveillance, Epidemiology, and End Results Program (SEER) database. Methods: We used the (SEER) database to identify the patients with non-gonadal germ cell tumors between 1998-2015. 1299 patients were identified and included in our analysis. Results: 1299 patients had non-gonadal germ cell tumors between 1998-2015. The mean age was 26 years-old. 568 patients (44%) were females and 731 patients (56%) were males. 276 patients (21%) died after a mean follow up time of 41.16 months (1-60 months). The mean overall survival (OS) was 49.4 months (95%CI 48.21-50.52) with the median being unreached. The Females had better OS compared to the males with a Hazard ratio (HR) = 0.50 (95%CI 0.40-0.63). Age more than 60 years-old at the time of diagnosis was associated with a substantially significant increase in mortality with an HR = 43 (95% CI 19.17-94.41). The mediastinal germ cell tumors were associated with worse OS compared to other sites with a HR = 4.69 (95%CI 3.37-6.52). The median OS for Embryonal cell carcinoma was 22 months, and it was associated with worse OS compared to seminoma and other histological subtypes with a HR = 4.10 (95% CI 1.69-9.72) and 2.77 (95% 1.16-6.58) respectively. On the other hand, Seminoma was associated with better OS compared to other histological subtypes with an HR = 0.66 (95%CI 0.52-0.84). Moreover, tumor size less than 80 mm was associated with better OS with a HR = 0.42 (95%CI 0.30-0.64). In multivariate analysis, patients above the age of 60 had worse OS with an HR = 4.04 (95%CI 1.71-9.58), patients with mediastinal germ cell tumors had poorer OS compared to other sites with an HR = 2.38 (95%CI 1.51-3.79). Furthermore, embryonal carcinoma, mixed germ cell tumors and choriocarcinoma were associated with worse OS compared to seminoma and immature teratoma with an HR = 10.39 (95% CI 4.36-24.72), HR = 2.07 (95% CI 1.23-3.46) and HR = 6.16 (95%CI 2.98-12.74) respectively. Conclusions: Non-gonadal seminoma and immature teratoma carry better prognosis compared to other histological subtypes. Also, among non-gonadal germ cell tumors, non-mediastinal seminoma has the best survival outcome.
Prognostic value of serum C-reactive protein level prior to second-line treatment in intermediate risk metastatic renal cell carcinoma patients.
Authors: Takamatsu Kimiharu , Mizuno Ryuichi , Hayakawa Nozomi , Kikuchi Eiji , Kosaka Takeo , Oya Mototsugu 
Published: May 2019

e16065 Background: The later-line treatment of metastatic renal cell carcinoma (mRCC) has been drastically changing by the development of immune-oncology drugs and molecular targeted treatment in recent years. Although the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model is useful for second-line setting, this model has the problem that over 50% patients are classified as intermediate risk group. The aim of this study is to evaluate whether the serum C-reactive protein (CRP) levels prior to second-line treatment could divide intermediate risk group patients. Methods: We retrospectively reviewed 150 mRCC patients received second-line molecular targeted therapy. We assessed the prognostic impact of serum CRP levels prior to second-line treatment initiation to predict overall survival (OS) especially in intermediate risk group. Results: The median OS from second-line treatment of whole cohort and intermediate risk group were 24.6 (95%confidence interval, 95%CI:18.2-31.0) and 23.6 (95%CI:15.1-32.1) months. Thirty-three out of 82 (40%) intermediate risk patients demonstrated elevated baseline CRP levels. The median OS of elevated and non-elevated CRP group were 13.4 (95%CI:5.9-20.8) and 29.4 (95%CI:25.5-33.5) months, respectively (p = 0.001). The serum CRP elevation could predict prognosis in intermediate risk patients treated with second-line treatment (HR 2.5,95%CI:1.4-4.2, p = 0.001). Conclusions: The serum CRP levels at second-line treatment initiation could divide intermediate risk mRCC patients into two prognostic subgroups.
Renal cell carcinoma in kidney transplant recipients at Guy’s and King’s College Hospital (UK) between 1987-2018.
Authors: Butt Sabeeh-Ur-Rehman , Chow Barbara , Shah Sapna , MacDougall Iain , Shaw Catriona , Kirmizis Dimitrios , Chowdhury Simon , Rudman Sarah Maria , Josephs Debra Hannah , Zakri Rhana , Olsburgh Jonathon , Enting Deborah 
Published: May 2019

e16066 Background: The increased incidence of cancer after renal transplantation is well recognised. Differences in cancer risk depend on the type of cancer but overall the incidence of solid cancer in kidney transplant recipient is at least twofold. Long term immunosuppression, oncogenic viruses and changes in immune surveillance are contributing factors. The incidence of renal cell carcinoma (RCC) is approximately six-fold greater than in the general population. Screening for RCC in the post-transplantation setting is not routine. Methods: Retrospective case series of kidney transplant recipients who underwent transplantation between 1987 and 2018 at Guy’s Hospital (London, UK). Collected data on patients who developed RCC post-transplant included: baseline demographics, renal disease, transplant survival, tumour characteristics, cancer treatment and survival. Results: 2968 patients underwent kidney transplantation between 1987 and 2018 at our Centre. 52 patients (1.8%) developed RCC. 40 (74%) were male with a median age of 51 years. 37% (71%) were white and 12 (23%) were black. The causes of end stage kidney disease included IgA nephropathy, hypertension and polycystic kidney disease. Median time to RCC diagnosis after transplant was 9 years (range 0-27). 86% of patients presented with stage 1/2 tumours, with the majority (72%) occurring in native kidneys. Most underwent radical nephrectomy although 5 patients were managed with radiofrequency-ablation (RFA) or surveillance (donor kidneys). Of 6 patients with metastatic disease, 5 received pazopanib and 1 everolimus. 4 patients continued systemic therapy for over 3 months and all derived clinical benefit with a median drug exposure of 19 months .15 patients required further kidney transplant or dialysis. Overall only 2 patients died from RCC. Conclusions: This retrospective study is the largest single-centre UK study to our knowledge. Kidney transplant recipients experience a marked increased risk of developing RCC. Most diagnosed RCCs are small and disease-specific mortality is low. With a third of tumours arising in donor organs, questions around optimum loco-regional approach and screening of high-risk population remain unanswered.
Real life data from Turkey regarding the impact of first-line sunitinib and pazopanib in metastatic renal cell cancer.
Authors: Isik Ulas , Kostek Osman , Demiray Gokcen , Dirican Ahmet , Simsek Melih , Büyüksimsek Mahmut , Ucar Gokhan , Gunaydin Ulug Mutlu , Sakalar Teoman , Aliyev Altay , Demir Atakan , Turhal Serdar , Pilanci Kezban Nur , Kefeli Umut , Gokyer Ali , Paydas Semra , Uncu Dogan , Okten Ilker Nihat , Uygun Kazim , Cabuk Devrim 
Published: May 2019

e16075 Background: Although the distribution in the world varies widely, renal cell carcinoma (RCC) is the ninth most common cancer, especially in males. It’s the seventh most common cancer in Turkey. In this study, the progression-free survival (PFS) and overall survival (OS) of patients with metastatic RCC (mRCC) who were treated at 13 centers in our country were evaluated and the efficacy of first-line treatment approaches was compared. Methods: Data of mRCC patients admitted to 13 outpatient clinics in Turkey between 2008 and 2018 were reviewed retrospectively. Demographic characteristics, pre-treatment clinical evaluations, information about treatment approaches and survival outcomes of the patients were collected. All medical records were collected by a detailed review of the patients’ charts. The median and percentage values were frequently signified for defining of central trends. Kaplan-Meier method was applied for OS analyzes and log-rank test with Cox-regression models were applied for the evaluation of prognostic factors. Results: Data from files of 262 patients were reviewed. Twelve of these patients were excluded from the study because they could not receive treatment due to comorbidities and other reasons at metastatic stage of the disease. Of the patients, 100 (40%) were female and 150 (60%) were male. Median age was 60 (range 21-83). For the entire group, the median PFS (mPFS) was 27.6 months and the median overall survival (mOS) was 46.1 months. In terms of first-line treatment of metastatic disease, 41.3% of the patients received sunitinib, 48.8% of the patients received pazopanib, 15.8% of the patients received other treatments. PFS of the patients receiving sunitinib, pazopanib and the other treatments were 26.3 months, 34.2 months and 14.2 months, respectively. There was no statistically significant difference between PFS of the patients receiving sunitinib and pazopanib (p = 0.05). mOS was 54 months in sunitinib arm, 54.9 months in pazopanib arm and 23.3 months in the other treatment arm. There was no statistically significant difference between two treatment agents in terms of mOS (p = 0.43). Conclusions: Pazopanib was more commonly prescribed in Turkey. There were no statistically significant differences between mPFS and mOS of the patients who received sunitinib and pazopanib for the first-line treatment of mRCC. With increased use of immunotherapeutic agents for the first-line treatment of mRCC in our country, improvement in mOS could be expected.
Immunotherapy with nivolumab in metastatic renal cell carcinoma in resource constraint settings: Impact of increasing intervals between standard doses, and stopping treatment early in responding patients.
Authors: Rauthan Amit , Patil Poonam , Yashas Nitin , Kulkarni Shriniwas Subhash , Sood Tanvi , Nigade Gaurav , Somashekhar S.P. , Zaveri Shabber 
Published: May 2019

e16078 Background: Nivolumab is now a standard 2nd line treatment for patients of metastatic Renal cell cancer (mRCC) who progress on 1st line Sunitinib or Pazopanib. Most western centers use Nivolumab for either 2 years duration, or indefinitely, or till severe side effects. Due to high drug cost and lack of insurance, it is difficult for most of our Indian patients to afford this duration of treatment. So, we decided to study the impact of increasing intervals between standard doses of Nivolumab, and stopping treatment early in responding patients of mRCC. Methods: This is a single centre, retrospective study of mRCC patients. Nivolumab was given at either 3 mg/kg or 240mg at 2 weekly intervals for the initial 6 cycles. If the patient were found to have either Complete Response (CR), Partial Response (PR) or stable disease, the interval between cycles was extended to 3 weeks (at same dose). After 9 months, the doses were extended to 4 weekly intervals (at same dose). The treatment was stopped at 18 doses in patients with CR or PR. The endpoints were objective response rate (ORR), overall survival (OS) and adverse events (AE). Results: Between May 2016 and Dec 2018, 28 patients received Nivolumab. 24 patients had received oral TKIs initially- 13 Sunitinib, 10 Pazopanib, and 1 Sorafinib. 4 patients received Nivolumab as 1st line therapy (2 as single agent, 2 with oral TKI). Response was assessed by RECIST criteria. 3 patients (11%) achieved CR, 7(25%) achieved PR, 7 (25%) had stable disease and 11(39%)had progressive disease. Treatment was stopped after 18 doses in the 3 patients who had CR. The duration of followup after stopping treatment ranges from 8 months to 18 months, and all 3 patients continue to be in CR. 3 patients with stable disease have received more that 18 cycles (1 at 22 cycles, 2 at 19 cycles). OS at 1 year is 60% and median OS has not been reached. Conclusions: In our experience, Nivolumab is an effective agent in mRCC, even when the dosage intervals are increased, and when the treatment is stopped early in responding patients. An ORR of 36% and a OS at 1 year of 60% is the best we have seen. Long-lasting responses, even after discontinuing therapy, have been seen. This enables us to reduce the cost of treatment without possibly losing efficacy, and this could be an important step forward for treating more patients with Nivolumab in our resource constraint setting.
Cardiovascular mortality in renal cell carcinoma: A population-based study.
Authors: Alevizakos Michail , Gaitanidis Apostolos , Appleman Leonard Joseph 
Published: May 2019

e16085 Background: Patients with renal cell carcinoma (RCC) often harbor risk factors for cardiovascular disease and may receive anti-VEGF agents, which are associated with cardiovascular toxicity. However, the risk for cardiovascular mortality in this patient population is currently unknown. Methods: Utilizing the SEER database, we identified patients with RCC diagnosed between 2007 (approval of sunitinib) and 2015 and selected patients aged ≥ 45 years. We calculated standardized mortality ratios (SMRs) for cardiovascular mortality (ICD-10 codes I00-I99) by comparing the number of observed deaths in the database to the number of expected deaths in age-matched groups of the US general population drawn from the CDC WONDER database. Multivariable Cox regression was used to identify risk factors for cardiovascular mortality in patients with RCC. Results: We identified 36,576 patients with RCC, of which 33,748 (92.3%) were ≥ 45 years old and among these, 1650 (4.9%) died of cardiovascular diseases. The SMR for cardiovascular mortality was 2.85 (95% CI 2.72-2.99) for all patients, 2.78 (95% CI 2.62-2.95) for males and 2.86 (95% CI 2.64-3.10) for females. Among the various age groups, the SMR was 4.75 (95% CI 3.82-5.84) for patients aged 45-54 years, 3.35 (95% CI 2.93-3.83) for patients aged 55-64 years, 2.75 (95% CI 2.49-3.04) for patients aged 65-74 years, 2.25 (95% CI 2.07-2.45) for patients aged 75-84 years, and 1.47 (95% CI 1.33-1.61) for patients aged > 85 years. In multivariate analysis, advancing age (HR 1.06, 95% CI 1.06-1.07), male sex (HR 1.18, 95% CI 1.05-1.33), black race (HR 1.48, 95% CI 1.27-1.73), stage IV disease (HR 1.21, 95% CI 1.01-1.45), and performance of surgery directed to the primary tumor (HR 0.33, 95% CI 0.29-0.38) were independently associated with cardiovascular mortality. Conclusions: Patients with RCC possess an almost 3-fold greater risk for cardiovascular mortality than the general population and this risk is even more pronounced in middle-aged patients. Aggressive management of modifiable cardiovascular risk factors in this patient population is thus warranted.
Systematic review and network meta-analysis of first-line treatments in mRCC.
Authors: Ratto Barbara Elizabeth , Chakraborty Sutirtha , Chinthapatla Harini , Kalra Manik 
Published: May 2019

e16086 Background: The approval of newer agents in metastatic renal cell carcinoma (mRCC) has changed the treatment paradigm in first-line settings. The aim of this review was to compare pazopanib against current first-line treatments in RCC. Methods: A systematic review was conducted that assessed pazopanib against first-line agents in treatment naïve patients with mRCC. Relevant databases and conferences were searched to identify randomized controlled trials (RCTs) assessing treatment naïve adult patient (≥18 years). Frequentist mixed treatment comparison (MTC) method was applied for the pairwise comparisons among treatments for ITT population and favorable, intermediate, and poor risk subgroups. Results: Twenty-three RCTs met the eligibility criteria. The MTC results showed that pazopanib was comparable to sunitinib in terms of progression free survival (PFS) and overall survival (OS) in ITT population. Cabozantinib was significantly better compared to pazopanib for PFS; however, there was heterogeneity in the patient population. Pazopanib was comparable to nivolumab + ipilimumab when assessed for PFS in ITT population; although, favorable risk patients treated with pazopanib achieved significantly higher PFS compared to nivolumab + ipilimumab (HR: 0.46, 95% CI: [0.37, 0.57]). Atezolizumab + bevacizumab and avelumab + axitinib were associated with significantly higher PFS compared to pazopanib. Cabozantinib and nivolumab + ipilimumab were associated with better OS compared to pazopanib. Conclusions: The newer agents i.e. cabozantinib and nivolumab + ipilimumab are approved for intermediate/poor risk patients. The results suggests that pazopanib is still a reliable option for treatment of patients in first-line settings, especially for favorable/intermediate risk patients.[Table: see text]
Effect of gender on the outcome of patients receiving nivolumab for metastatic renal cancer: Results from a large study population.
Authors: Procopio Giuseppe , Di Cosimo Serena , De Giorgi Ugo , Cartenì Giacomo , Cortesi Enrico , Caserta Claudia , Sabbatini Roberto , Bearz Alessandra , Buti Sebastiano , Pignata Sandro , Berruti Alfredo , Ruggeri Enzo , Bengala Carmelo , Livi Lorenzo , Fagnani Daniele , Bonetti Andrea , Mitterer Manfred , Ortega Cinzia , Cognetti Francesco , Di Nicola Massimo A. 
Published: May 2019

e16087 Background: Several studies, the majority on melanoma and lung cancer, have addressed the value of gender with respect to immune check point inhibitors outcome as compared to standard therapy, showing conflicting results. Nevertheless, few focused on gender-related clinical outcome and toxicity in renal cell carcinoma (RCC) patients. Methods: This analysis evaluated the effect of gender on overall survival and adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) v.4.0 in an expanded access programme of nivolumab 3 mg/kg once every 2 weeks in second-line and beyond metastatic RCC. Only patients assuming at least one dose of nivolumab were analyzed. Results: Of 389 patients analyzed, 25.2% were female. On study entry, no differences were found in women as compared to men in terms of age, on average 64 years, p = 0.91; overweight/obesity, 45 versus (vs) 49%, p = 0.47; LDH , mean U/L 391 vs 32, p = 0.17); and neutrophils/lymphocytes ratio> 3 (62 vs 63%, p = 0.87). Disease presentation was similar according to gender, although women tended to present less lung (66% vs 76%, p = 0.06) and bone metastases (42% vs 52%, p = 0.07). Notably, there was no differences in the IDMC prognostic model by gender (p = 0.94). Any drug related AEs (38 vs 30%, p 0.15), grade 3-4 (6% vs 6%) and median number of drug doses 12 (53% vs50%, p = 0.58 ) did not differ between gender. After adjusting for known prognostic variables, multivariate analysis showed that women had similar overall survival as compared to men (hazard ratio 0.81, 95% confidence interval 0.56-1.17, p = 0.26). Conclusions: Women demonstrate similar overall survival than men in metastatic RCC treated with secondal line and beyond nivolumab, with no differences observed in serious AEs and dose administered.
Nivolumab in renal cancer: French evaluation of use, current practices and medico economic approach.
Authors: Grude Francoise , Appéré Gildas , Marhuenda Fanny , Deniel Lagadec Delphine , Boughalem Elouen , Schlurmann Friederike , Travers Muriel , El Kouri Claude 
Published: May 2019

e16093 Background: Since April 2016 (EMA approval), Nivolumab could be prescribed in advanced renal carcinoma after prior treatment. The Brittany and Pays de la Loire Cancer Observatory has collected data on their real-life indications, current management, safety, efficacy and medico-economics. Methods: All non opposing adult patients with renal carcinoma initiated nivolumab (3 mg/kg q2w) in 2016 and 2017 were included. Minimum follow-up for survival was 12 months. Sex, age, performans status PS ECOG, toxicities, response rate, Progression Free Survival (PFS) and Overall Survival (OS) have been studied. Results: 141 pts were treated by nivolumab in 2016 and 2017 with a median age of 68 years old [39-94] and with 26% aged at least 75 years. The median number of courses was 7 [1-47]. 68 pts (48%) had 1 to 6 courses, 16 pts (11%) 7 to 12 courses, 25 pts (18%) 13 to 24 courses and 32 pts (23%) more than 25 courses. 81 (58%) pts were treated in 2nd line, 34 (24%) in 3rd line, and 25 (18%) in further lines. All lines combined, Complete Response (CR) was observed for 3 pts (2%), Partial Response (PR) for 26 pts (18%), Stable Disease (SD) for 36 pts (26%) (disease control DC : 46%) and disease progression for 51 pts (36%). For 25 pts (18%), nivolumab treatment has been stopped before first medical imaging. PS ECOG was 0-1 for 88 pts (62%), 2 for 21pts (15%), 3-4 for 8 pts (6%) and unknown for 24 pts. Median OS and PFS were 18.2 months and 3.2 months, respectively. No difference on survival has been noticed according to gender, treatment line, age (cut-off 70 or 75 yo) and grade III/IV toxicity. However, OS and PFS were significantly influenced by general health (p < 0.0001). PFS for PS 0-1 pts was 6.5 months, for PS2 2.3 months and for PS3-4 0.8 months. OS was not reached for PS0-1 pts, 3.8 months for PS2 pts and 0.8 months for PS3-4 pts. OS for patients with DC (RC+RP+SD) has not reached and PFS was 14.9 months respectively. 17% of patients presented grade III/IV toxicities. Nivolumab courses during the 2 years costed 5.1 millions of euros (drug, hospitalisation and transportation). 80% of this costs were dedicated to pts who experienced DC. Conclusions: In real life setting, survival outcomes and toxicities with nivolumab in advanced renal carcinoma are comparable to literature’s data. ECOG PS≥2 pts presented shorter survival than PS0-1 pts. Interestingly, 80% of the cost incurred for these treatments benefited to pts with DC. Updated survival data will be available be shown at the meeting.
Time to surgery (TTS) in renal cell carcinoma (RCC): Predictors and association with overall survival (OS).
Authors: Kommalapati Anuhya , Tella Sri Harsha , Tandra Pavankumar 
Published: May 2019

e16107 Background: Guidelines recommend surgical resection of primary tumor in stages 1-3 RCC. TTS refers to the time frame from the initial diagnosis to surgical resection of primary tumor. Shorter TTS has shown OS benefit in breast, head and neck cancers whereas longer TSS was shown to be acceptable in colon cancer. However, no such data exists for RCC. Using National Cancer Data Base (NCDB), we sought to determine the factors associated with TTS and its effect on OS. Methods: Patients with RCC who underwent partial or total nephrectomy were included, excluding those received neoadjuvant therapy. Logistic regression model was utilized to evaluate relative risk of delayed TTS. OS in association with TTS was estimated using the Kaplan-Meier method and Cox multivariate analysis (MVA). Results: A total of 60,198 RCC patients met the inclusion criteria. In contrast to a prior study that showed a median TTS of 41 days our study showed a median TTS of 35 days. We dichotomized the TTS as ≤ 35 days or ≥ 36 days. On MVA, TSS ≥ 36 days had significantly better OS (HR: 0.95 [CI:0.92-0.99], p < 0.01). Factors associated with TSS ≥ 36 days were race, insurance, higher Charlson score, lower grade, and getting managed at academic facilities and Pacific region (p < 0.01) (Table). Conclusions: A longer TTS with RCC is understandably associated with greater comorbidity, and non-private insurance, but questionably so in race, ethnicity, and facility related factors. However, given that TTS ≥ 36 days was not associated with higher risk of death, it may indicate that a reasonable delay could be pursued in certain cases for more accurate preoperative evaluation. [Table: see text]