bluuebunny/crossref_metadata_2025_split huggingface dataset:
A single center experience of the impact of treatment-related toxicity in the clinical outcomes of elderly patients with metastatic germ cell tumors.
Authors: Sharma Anand , Palmer David , Brown Hannah , Merrick Sophie , Gogbashian Andrew , Vasdev Nikhil , Pullar Ben , Hall Marcia 
Published: May 2019

e16048 Background: Germ cell tumours (GCT) are predominantly a disease of the young, with < 10% of cases being diagnosed at ≥45 years. Platinum based chemotherapy is the gold standard in treating these patients. Data regarding outcomes and treatment toxicities in elderly patients is lacking. We studied the efficacy, toxicities and survival rates in a cohort of men diagnosed with GCT aged ≥45 years receiving chemotherapy in a metastatic setting. Methods: Data was collected retrospectively from 48 patient’s ≥45 years with GCT’s identified at Mount Vernon Cancer Centre, London. The histology, stage and international germ cell consensus (IGCC) risk classification was identified in all patients. Data was collected regarding chemotherapy regimens, number of cycles completed, toxicities and complications that led to treatment modifications or early cessation. Treatment toxicities were evaluated using the common terminology criteria for adverse events (ctCAE) grading. We then assessed progression free survival, relapse rates and overall survival (OS). Results: We identified 48 patients diagnosed with GCTs aged ≥45 years. The median age at diagnosis was 52 (range 45-70) and 75% of patients were aged ≥50. Classic seminoma and nonseminomatous GCTs were seen in 65% and 35% of patients, respectively. 75% of patients were ≥stage II at diagnosis. In total 29 patients received BEP, 4 EP, 7 Carboplatin AUC10, 2 Carboplatin AUC7 and 5 received POMBACE. 73 % (35/48) of patients experienced one or more complication/s from chemotherapy (15/48 ctCAE grade ≥3), of which the most common were neuropathies (27%), thromboembolism (10%) and tinnitus (10%). In 8 cases omissions or dose reductions had to be made and treatment delays occurred in 3 cases. Only 2 patients did not complete all intended cycles. Over 70% (35/48) of patients had an OS of > 5 years. One patient died during chemotherapy due to gastro-intestinal bleed. Conclusions: Survival rates in patients with GCTs aged ≥45 treated with chemotherapy are good with the majority achieving a > 5 year OS. Although age is not a prognostic factor, these patients are more prone to toxicities and have underlying comorbidities. This data will be of value to oncologists weighing up the risks versus benefits of treatment in this older cohort of patients in combination with similar studies.
Health related quality of life analysis among testicular germ cell tumor survivors treated in a tertiary cancer hospital in India.
Authors: Raj Abhishek , Kumar Lalit , Sharma Atul , Pramanik Raja , Batra Atul , Seth Amlesh , Ray Mukurdipi , Haresh KP , Kaushal Seema , Sahoo Ranjit 
Published: May 2019

e16057 Background: Testicular Germ Cell Tumor (TGCT) is a highly curable malignancy treated with surgery, radiotherapy and chemotherapy. The available literature has conflicting results on quality of life (QoL) of survivors determined using various tools. There is no Indian data on QoL among TGCT patients. Methods: The study was a prospective case-control study. EORTC QLQ-C30 questionnaire were administered to survivors (last treatment completed at least 2 years back) and healthy age matched controls attending the uro-malignancy clinic of AIIMS between 1st January 2017 to 31st December 2018. The functional, symptom and global QoL scales were scored as per EORTC manual and were compared with each other using student t-test and Mann-Whitney test. The data was analysed with stata v.13.0. Results: The mean scores of all domains of functional scales and global QoL of 114 TGCT survivors were significantly worse than 100 controls except role functioning and cognitive functioning (Table). The symptom scores of cases were significantly worse for each domain except insomnia and constipation (Table). There was no difference in QoL parameters between Seminoma or Non-Seminoma or different stages of GCT. Conclusions: The QoL among TGCT survivors was significantly inferior indicating the long term physical, emotional, social, sexual and financial effects of disease and its treatment on survivors. More robust tools and studies are needed to better define QoL among survivors. ± SD of Functional, symptom and Global QoL Scales) [Table: see text]
Improved outcomes in testicular germ cell tumor patients treated at the referral center in Slovakia in the last decade.
Authors: Chovanec Michal , Rejlekova Katarina , Sycova-Mila Zuzana , Obertova Jana , Palacka Patrik , Hapakova Nikola , De Angelis Valentina , Kalavska Katarina , Svetlovska Daniela , Pindak Daniel , Mardiak Jozef , Mego Michal 
Published: May 2019

e16059 Background: Treatment at expert centers results in superior survival in patients with germ cell tumors (GCTs). This study evaluated outcomes in patients treated at National Cancer Institute in Slovakia before and after the year 2008 after refining the treatment strategies. Methods: Our institutional database was searched for GCT patients treated at National Cancer Institute in Slovakia between 1992 and 2016. A year of 2008 was selected for cutoff to compare changes in outcomes before and after this time-point due to refining treatment strategies such as centralization of post-chemotherapy surgery and incorporation of granulocyte-colony stimulating factor (G-CSF) for routine prophylaxis of febrile neutropenia. Kaplan-Meier product limit and log-rank test were used for statistical analysis. Results: This retrospective study included 485 patients treated for metastatic GCT. Two hundred and sixty-three patients (54%) were treated before 2008 (group 1) and 222 patients (46%) were treated after 2008, including (group 2). Progression-free survival (PFS) and overall survival (OS) was significantly improved in group 2 vs 1 (HR = 0.63, 95% CI 0.46-0.87; P= 0.0039 for PFS and HR = 0.44, 95% CI 0.30-0.65; P = 0.0003 for OS, respectively). In a subgroup analysis of International Germ Cell Cancer Collaborative Group criteria, favorable change in survival was observed in good-risk GCTs (HR = 0.40, 95% CI 0.24-0.67; P = 0.0009 for PFS, and HR = 0.20, 95% CI 0.10-0.38; P = 0.0002 for OS), but nor in intermediate or poor risk group. Conclusions: Treatment outcomes of GCTs have significantly improved in the last decade at our institution. We hypothesize that changes in treatment approach contributed to this improvement including centralization of post-chemotherapy retroperitoneal lymph-node dissections and routine use of granulocyte-colony stimulating factors that have been implemented in 2007. Referral bias for extremely poor risk patients in recent years may be an accounting factor for lack of improvement in this subgroup.
Efficacy and safety profile of sunitinib as a first line treatment for advanced/metastatic clear-cell renal cell carcinoma: Pooled analysis of randomized controlled trials.
Authors: Haykal Tarek , Samji Varun , Zayed Yazan , Al-Dulaimi Ragheed , Gakhal Inderdeep , Bala Areeg , Sotzen Jason , Ghamrawi Ranine , Katato Khalil , Danish Rizwan 
Published: May 2019

e16067 Background: Metastatic clear-cell renal cell carcinoma (RCC) is largely incurable, and its treatment remains challenging. Sunitinib, a tyrosine kinase inhibitor, is one of the current standard-of-care options for treatment-naïve patients with metastatic RCC. Despite the proven efficacy of Sunitinib, prolonged treatment with some tyrosine kinase inhibitors (TKIs) has been associated with significant adverse events (AEs). Therefore, we aimed to calculate the exact efficacy in addition to the prevalence of all AEs of Sunitinib in a pooled analysis from all available randomized controlled trials (RCTs). Methods: A comprehensive electronic database search was conducted for all RCTs comparing the clinical outcomes and adverse events of Sunitinib versus all other available treatments for treatment-naïve advanced/metastatic clear-cell renal cell carcinoma. We then calculated the pooled outcomes and prevalence of the most common reported side effects of Sunitinib. All statistical analyses were performed using R Statistical Software v3.4.0 (R Foundation, Vienna, Austria). Results: We included 8 RCTs, with a total of 4106 patients. The mean age was62, with 66.44% males.The efficacy of Sunitinib was reported as 3 main outcomes: Median progression free survival at 10.73 [7.76, 13.7] months, median overall survival at 23.28 [16.74, 29.81] months and the estimated objective response rate at 25[13, 37] %. Any grade AEs were reported in 72% of patients with the following frequencies: fatigue 44%, diarrhea 38%, nausea 31%, hand-foot syndrome 30%, hypertension 27%, dysgeusia 25%, hypothyroidism25%, constipation 20%, stomatitis 20%, inflammation of the mucosa 18%, dyspepsia 16%, vomiting 14%, rash 12%, asthenia 11%, and epistaxis10%.Grade 3&4 (severe) AEs were reported in 52% of patients with the following frequencies: hypertension 9%, fatigue 8%, hand-foot syndrome 5%, asthenia 5%, diarrhea 4%, and inflammation of the mucosa 2%. Conclusions: Despite Sunitinib being one of the current standard treatments for patients with metastatic/advanced clear-cell RCC, with well-described efficacy, its safety profile is still concerning with a significant prevalence of reported grade 3-4 AEs of 52% of the treated patients in the included RCTs. These findings underscore the importance of the emergence of newer drugs and treatment plans for patients with metastatic RCC, not only to achieve similar or better clinical outcomes but also to decrease the percentage of grade 3-4 AEs.
Molecular profile of early-stage and advanced-stage of renal cell cancer in China.
Authors: Chen Jimin , Zhang Yanrui , Yang Tongtong , Wang Huina , Guo Jing , Liang Xiayuan , Lou Feng , Cao Shanbo , Du Chuanjun 
Published: May 2019

e16071 Background: The mutation spectrum has been extensively studied in Renal Cell Cancer (RCC), a heterogeneous disease. While major investigations have focused on metastatic RCC (mRCC). This study intended to explore the molecular characteristics between early-stage (stage I/Ⅱ) and advanced-stage (Ⅲ/Ⅳ) of RCC patients (pts). Methods: 36 tumor specimens were obtained from individual pts diagnosed RCC, including 22 tissues paired with blood samples. Somatic mutations were identified via targeted next generation sequencing with Acornmed panel including 808 genes associated with tumor development. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (InDels), copy number alterations (CNA) and chromosomal rearrangements. Clinical data of a cohort from TCGA who had RCC was collected and analyzed. Results: Among the 36 pts enrolled, 61% were early-stage group and 39% were advanced-stage group. The most frequently mutated genes in RCC were VHL (50%), PBRM1 (14%), BAP1 (11%), TP53 (11%) and PIK3CA (6%). Truncating mutations were the most frequent alterations accounting for 66% (33/50) of genetic alterations. Mutations in VHL, BAP1, PBRM1 and TP53 were shared by both early and advanced RCC. While mutations in PIK3CA, CDKN2C, EGFR, FAMCA, GRIN2A, KDM6A, SOX17, TSC1 and APC were only detected in early stage group. KNSTRN, KRAS, MYD88, NF2, ATM, PTEN and STAT5B mutations were only detected in advanced group. Among 22 plasma samples, genomic alterations were detected in 40.9% (9/22) of pts postoperatively, such as TP53, PIK3CA, PTEN, and APC. Functional annotation clustering revealed that 4/9 in these genes were tumor suppressors, which negatively regulated apoptosis. Pts with genomic alterations in TP53 (p = 0.0034), PIK3CA (p = 0.0015) or PTEN (p = 0.00017) had worse OS significantly (TCGA). Conclusions: VHL, PBRM1, BAP1 were the most important driver genes mainly detected in all stages of RCC. The heterogeneity between early and advanced-stage may be related with clinical status. Gene alterations in plasma ctDNA postoperatively should have the potential to stratify patients with different prognostic outcome.
Association of body mass index and systemic inflammation index with survival in patients with renal cell cancer treated with nivolumab.
Authors: De Giorgi Ugo , Procopio Giuseppe , Sabbatini Roberto , Caserta Claudia , Mitterer Manfred , Ortega Cinzia , Scoppola Alessandro , Fornarini Giuseppe , Ferraú Francesco , Marchetti Paolo , Verusio Claudio , Mini Enrico , Bidoli Paolo , Buti Sebastiano , Crino Lucio , Basso Umberto , Frassoldati Antonio , Bearz Alessandra , Carteni Giacomo , Sternberg Cora N. 
Published: May 2019

e16077 Background: Body mass index (BMI) and inflammation indexes are easily evaluated, predict survival in many tumors, and are potentially modifiable. The "obesity paradox" of longer survival in cancer patients with high BMI has been explained by altered fatty acid pathways, which could have an impact in immune-inflammatory function, and leptin-driven increase in T cell aging resulting in higher PD-1 expression and dysfunction, which leaves tumors notably more sensitive to checkpoint blockade. We evaluated the potential association of inflammatory indexes and BMI with the clinical outcome of metastatic renal cell carcinoma (mRCC) undergoing immune checkpoint inhibitor therapy. Methods: A prospective cohort of patients with mRCC treated with nivolumab enrolled in the Italian Expanded Access Program (EAP) from July 2015 through April 2016 was examined. Reference measures of inflammation were identified for neutrophil to lymphocyte ratio (NLR) < /≥3, systemic immune-inflammation index (SII) < /≥3 and platelet to lymphocyte ratio (PLR) < /≥232. Patients were classified as high BMI (≥25 kg/m2) versus normal BMI ( < 25 kg/m2). Results: Among 313 evaluable patients, 289 (75.1%) were male, median age was 65 years (range, 40 to 84), with 105 (24.9%) ≥70 years. In univariate analysis, age ≥70 years, performance status, BMI, SII, NLR and PLR were able to predict outcome. In multivariate analyses, SII ≥1375, BMI < 25 and age ≥70 years independently predicted OS (HR, 2.96; 95% CI, 2.05-4.27; HR, 1.59; 95% CI, 1.10-2.30 and HR, 1.65; 95% CI, 1.07-2.55, respectively). Under the model of independent effects, a patient with both SII ≥1375 and BMI < 25 was estimated to have much worse OS (HR, 3.37; 95% CI, 2.29-4.95, p < 0.0001) than a patient with neither or only one risk factor. SII changes at 3 months predicted OS (P < 0.0001). Conclusions: BMI combined with inflammation tripled the risk of death, suggesting that these biomarkers are critical prognostic factors for OS in patients with mRCC treated with nivolumab.
Efficacy of systemic therapy for metastatic renal cell carcinoma in patients over 75 years of age.
Authors: Mizuno Ryuichi , Takamatsu Kimiharu , Hayakawa Nozomi , Kosaka Takeo , Tanaka Nobuyuki , Oya Mototsugu 
Published: May 2019

e16080 Background: In the last decade, approval of targeted agents and immune checkpoint inhibitors (ICI) have dramatically changed the scenario of systemic treatment of metastatic renal cell carcinoma (mRCC) with improved survival. Although elderly individuals represent a consistent proportion, clinical trials have not directly compared the efficacy and safety of targeted agents in the elderly population. Methods: A total of 195 patients were retrospectively reviewed. All patients received systemic therapy for mRCC at Keio University hospital in Japan (Institutional review board approval No 2013-0425). Patients were divided into two groups (≥75 or < 75 years) according to their age at the time of systemic therapy initiation. The disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) were compared between the two cohorts. Results: The elderly cohort (≥75 years old) comprised of 42 patients (21.5%). The DCR for first line treatment in patients ≥75 years old and < 75 years old was 75.0 and 76.2 %, respectively (p = 0.8728). The median PFS for first line treatment in patients ≥75 years old and < 75 years old was 10.7 (95% CI 7.5–20.7) and 11.6 (95% CI 9.7–16.3) months, respectively (p = 0.6074). The median OS for systemic treatment in patients ≥75 years old and < 75 years old was 37.3 (95% CI 18.0–65.2) and 45.5 (95% CI 35.1–56.8) months, respectively (p = 0.0424). Conclusions: Systemic treatment for mRCC was feasible and effective in Japanese patients over 75 years of age.
Patient-reported experience of diagnosis, management, and burden of renal cell carcinomas: Results from a global patient survey in forty-three countries.
Authors: Giles Rachel H , Maskens Deb , Bick Robert , Martinez Robin , Packer Malcolm , Heng Daniel Yick Chin , Larkin James M. G. , Bex Axel , Maclennan Sara Jane , Jewett Michael A.S. , Jonasch Eric 
Published: May 2019

e16091 Background: The International Kidney Cancer Coalition (IKCC) is a federation of 38 affiliated patient organizations representing 1.2 million patients worldwide that is committed to reduce the global burden of kidney cancer. A large-scale global survey of RCC patients to capture real world experiences (RWE) has never been undertaken. Methods: The 35-question survey was designed to identify geographic variations in patient education, experience and awareness, access to care, best practices, quality of life, involvement in clinical trials and to highlight unmet needs. The survey was conducted online or in paper form in Sept-Oct 2018 by kidney cancer patients and /or their caregivers identified by IKCC’s Affiliate Organizations and through social media in 14 languages. Results: 1,983 responses were recorded from 43 countries. Analysis revealed that at diagnosis, 43% of all respondents had no understanding of their RCC sub-type; patients with clear cell carcinoma (64%) had a notably poorer understanding of their RCC subtype than did patients with rarer RCC subtypes. While 96% of respondents reported psychosocial impacts, surprisingly, only 50% disclosed them to their healthcare team. Of the 70% of patients who were never asked to participate in a clinical trial, 89% responded they would have “fairly likely” done so if asked. RCC patients < 45 years old reported nearly twice as many barriers to treatment as patients > 45 at diagnosis. Females reported longer delays to diagnosis than males. Shared decision making remains aspirational across major cancer centers and community hospitals: globally 29% of all patients reported no involvement in their treatment decision, responding ‘my doctor decided for me’. Conclusions: This exploratory research sheds light on the unmet needs in the RCC patient experience and warrants further analysis. This first-ever global survey serves as a benchmark for longitudinal data collection. RWE indicates opportunities to improve communication about diagnosis, psychosocial impacts, and clinical trials. [Table: see text]
Unraveling the molecular profile underpinning pancreatic tropisms in metastatic clear cell renal cell carcinoma.
Authors: Singla Nirmish , Onabolu Oreoluwa , Woolford Layton , Stevens Christina , Tcheuyap Vanina , McKenzie Tiffani , Yousuf Qurratulain , Ma Yuanqing , Choi Jacob , Zhang Ze , Xie Zhiqun , Wang Tao , McKay Renee , Christie Alana , Pedrosa Ivan , Przybycin Christopher , Kapur Payal , Rini Brian I. , Brugarolas James 
Published: May 2019

e16096 Background: The tropism of cancer metastases is poorly understood yet holds prognostic value. Clear cell renal cell carcinoma (ccRCC) exhibits a broad pattern of metastases, making it an optimal model to study organotropism. Notably, when ccRCC metastasizes to the pancreas (PM) independently of other sites, it is associated with favorable outcomes in patients for unclear reasons. Here, we comprehensively analyzed the clinical and molecular profile of patients with PM. Methods: RCC patients with PM from UTSW and Cleveland Clinic were identified. Clinicopathologic data and oncologic outcomes were analyzed. Whole exome sequencing (WES), RNAseq, and histologic assessment of primary and metastatic tumors from PM patients were conducted. Results: 31 RCC patients with PM were identified. We observed remarkably favorable outcomes in our PM cohort, with a median overall survival (OS) of 10.7 years from metastatic diagnosis and a long latency between initial diagnosis and development of metastasis (median 69 months in patients who were non-metastatic at diagnosis). OS was independent of both metastatic tumor burden and known IMDC prognostic factors. We discovered that tumors from PM patients were markedly uniform and clustered together by gene expression analysis. WES and DNA copy number analyses revealed a high frequency of VHL and PBRM1 mutations, 3p loss, and 5q amplification, along with a lower frequency of 9p, 14q and 4q losses and BAP1 mutations, characteristic of indolent ccRCC. Furthermore, the genomic and histologic features of tumors from patients with PM can be recapitulated in patient-derived xenograft models. Conclusions: To our knowledge, this is the first report to unravel molecular determinants of organotropism, and we highlight that organotropism can be an independent prognostic factor. Understanding tumor heterogeneity may help refine prognostic models for metastatic RCC and hold implications for improved personalization of therapy.
Comparison of efficacy and safety of checkpoint inhibitors in patients with genitourinary cancers aged below and above 75 years.
Authors: Schulz Gerald Bastian , Szabados Bernadett , Spek Annabel , Staehler Michael D. , Stief Christian , Casuscelli Jozefina 
Published: May 2019

e16101 Background: Checkpoint-inhibitors have recently been introduced in the treatment of patients with genitourinary cancers. However, the use in elderly patients is controversial due to putative age-associated changes including the dysregulation of the immune system. We sought to investigate the safety and efficacy of immunotherapy in patients younger and older than 75 years of age. Methods: We conducted a retrospective review of patients with renal cell carcinoma and urothelial cancer treated with different immunotherapeutic agents between August 2015 and September 2018 at a high-volume single institution. Eligible patients received at least one cycle of single agent or a combination of checkpoint inhibitors as first or following treatment line. Immune-related adverse events (irAE) were graded using the NCI CTCAE v 4.0. Clinicopathological parameters including gender, cancer entity, ECOG, adverse events, comorbidities and response to treatment were stratified by age ≥ 75 vs. < 75 years and tested with a Pearson's chi-squared test. Additionally, we evaluated the impact of irAE on oncological outcome using the log-rank test. Results: 79 patients were identified, of those 27 (34.2%) were 75 years and older (15 renal cell carcinoma and 12 urothelial cancer patients) and 52 (65.8%) were younger than 75 years (39 renal cell carcinoma and 13 urothelial cancer patients). 2 complete responses were achieved in the elderly group and 6 in the younger group (p = 0.56). Disease control rate (stable disease, partial and complete response) was 48,1% in the elderly group and 53.8% in the younger group (p = 0.631). We observed a total of 30 irAEs (18 grade 1-2 and 12 grade 3-4), with an even distribution among the groups (≥75 years: 1 grade 4 AE; < 75 years: 12 grade 3-4 AEs). Except for ECOG ≥2 (p = 0.009) and ≥2 comorbidities (p < 0.001), there was no difference when groups were stratified by age. Both disease control rate and irAE did not differ between age subgroups. Occurrence of irAE showed no impact on oncological survival. Conclusions: The study demonstrates that patients over 75 years of age with renal cell and urothelial cancer treated with checkpoint-inhibitors respond with a good toxicity profile and an efficacy comparable with the younger population. irAE seem to have no impact on prognosis.