bluuebunny/crossref_metadata_2025_split huggingface dataset:
The clinical presentation, diagnosis, treatment and long term outcome of germ cell tumor in 85 patients with Down syndrome.
Authors: Weatherford Emma , Wang Jue 
Published: February 2018

554 Background: The main objective of this study was to determine the clinical features, treatment, clinical outcome and prognosis of Down's syndrome (DS) patients with germ cell tumor (GCT). Methods: Literature search based on PubMed search was performed using the following keywords: “Germ cell tumor (GCT)” and “Down's syndrome”. A total of 85 cases of GCT in DS patients published in literature between January 1985 and October 2017 were identified. Results: Our final cohort of GCT in DS include 44 cases of testicular germ cell tumor (TGCT); 22 intracranial GCT, 2 primary mediastinal GCT, 3 gastrointestinal GCT, 9 retroperitoneal GCT, and 5 cases of ovarian GCT. The median age of forty-four testicular GCT was 30 years (range 2 years – 50 years). In most cases, cancer was diagnosed following the discovering of swelling by care provider or found incidentally (either painless or painful) in the region of the testes, although abdominal pain was a symptom in a few cases. 29 (66%) patients were diagnosed with seminoma and 15 (34%) with non-seminoma. In the seminoma group, 18 (62%) patients were diagnosed with stage I , 9 (31%) with stage II and 2 (7%) with stage III. In the non-seminoma group, 4 (27%) patients were diagnosed with stage I, 5 (33%) with stage II and 6 (40%) with stage III. Nearly all patients (94%) underwent orchiectomy. 52% patients received chemotherapy, with BEP being the most common administered regimen. 7 patients had retroperitoneal lymph node dissection ( RPLND). In the seminoma group, there were 5 deaths, 3 related to disease progression, 2 related to comorbidities, 1 died during chemotherapy. In the non-seminoma group, there were 2 deaths, 1 related to disease progression, 1 died during chemotherapy. The overall survival at 5 years for stage I was 100%, 76% for stage II and 68% for stage III. Conclusions: In this largest cohort of GCT in DS, we found TGCTs are often diagnosed at stage II or III. In addition, delayed diagnosis, comorbidities likely contributed to the inferior outcome in stage II/III TGCTs in patients with DS. Emphasis on education, better communication, early screening and detection, are needed to improve the outcome in this population.
A longitudinal assessment of health-related quality of life in patients undergoing active surveillance for early prostate cancer in Japan (PRIAS-JAPAN).
Authors: Kato Takuma , Sugimoto Mikio , Hirama Hiromi , Kakehi Yoshiyuki , Yamaguchi Akito , Abe Takashige , Maruyama Satoru , Mitsuzuka Koji , Arai Yoichi , Fukuhara Hiroshi , Sasaki Hiroshi , Egawa Shin , Ninomiya Iku , Hashine Katsuyoshi ,   PRIAS-JAPAN Investigators
Published: February 2018

56 Background: There are few reports of the health-related quality of life (HRQOL) of Asian prostate cancer patients who choice active surveillance. We evaluate HRQOL in participants of the Prostate Cancer Research International Active Surveillance study (PRIAS-JAPAN). Methods: The participants’ general HRQOL was assessed longitudinally using the Short Form 8 Health Survey (SF-8) at enrollment and annually thereafter until discontinuation of active surveillance (AS). We compared the quality of life and baseline score of participants with that of the general population (Norm-based scoring [NBS] 50) using paired t-test and the mixed models. Age-adjusted logistic regression was applied to the 3-year AS remaining rate. Results: The SF-8 questionnaire was administered to 570 patients (median age, 68 [range, 45–87] years). We evaluated 484, 328, 140, 84, and 68 patients at enrollment and 1, 2, 3, and 4 years thereafter. At enrollment, the mean physical component summary (PCS) score and all subscales revealed better HRQOL than NBS. No significant difference was noted in mental component summary (MCS) compared to NBS at enrollment. However, MCS at 1, 2, and 4 years was higher than the NBS. PCS slightly diminished in 4 years, whereas MCS at all time points showed no change. Age-adjusted logistic regression showed an OR of 1.66 (95% CI: 1.047–2.632, P = 0.0313) on 3-year AS remaining rate in favor of patients with above median MCS at enrollment. Conclusions: Men who were enrolled into the PRIAS-JAPAN study had better HRQOL than that of NBS. PCS decreased but MCS did not. The AS remaining rate was influenced by baseline MCS.
Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Results from the NIVOREN GETUG-AFU 26 study.
Authors: Albiges Laurence , Negrier Sylvie , Dalban Cécile , Gravis Gwenaelle , Chevreau Christine , Oudard Stephane , Laguerre Brigitte , Barthelemy Philippe , Borchiellini Delphine , Gross-Goupil Marine , Geoffrois Lionnel , Brihoum Meryem , Escudier Bernard ,   GETUG
Published: February 2018

577 Background: Nivolumab (N) has been approved for the treatment of mRCC after failure of 1 or 2 tyrosine kinase inhibitors (TKI) based on the results of Checkmate 025 study. Right after approval, we initiated the NIVOREN GETUG-AFU 26 study (NCT03013335), a French multicenter prospective study to evaluate safety and efficacy of N in a “real world setting”. Methods: Patients (pts) with clear cell mRCC could be enrolled if they had received at least one TKI. Compared with the pivotal trial, inclusion criteria allowed patients with more than 2 previous lines of treatment, including previous mTOR inhibitors, ECOG PS 2, asymptomatic brain metastases (BM) or impaired renal function. The primary objective of the study was the safety of N, efficacy being the main secondary objective. Between February 2016 and June 2017, 729 pts have been enrolled. We report the results from the first 528 pts. Results: All pts had clear cell mRCC, median age was 64, 77.2% were male. ECOG PS was > 1 in 73 pts (14.7%), 27.5% pts had received prior everolimus, 29.7% pts had received more than 2 previous lines, IMDC risk groups were 19%/54.9%/26.1% for good/intermediate and poor risk respectively; 69 (14%) pts had BM at screening. With a median follow up of 13.1 months, median duration of treatment was 4.1 months [0-15.6], with 31.4% of pts still on therapy. Treatment discontinuation due to adverse event (AE) occurred in (48) 13.3% pts . 64 serious related AE have been reported in 52 pts (9.9%) including 7 renal failures and 6 pneumonitis. Median PFS was 4.4 months 95%CI[3;4.6] . At the time of this analysis, 170 pts have died and 12 months OS rate was 66.4% 95%CI[ 61.7; 70.7]. In subgroups analysis, ECOG-PS > 1 (Hazard Ratio (HR) = 2.450 [1.704;3.523]), more than 2 previous lines (HR = 1.442 [1.059;1.963]) and prior use of everolimus (HR = 1.704 [1.250;2.322]) were associated with reduced OS in univariate analysis. Conclusions: We report the first analysis of the largest prospective real world setting study of N in mRCC. NIVOREN study demonstrates that N safety and efficacy in a “real world” prospective study are comparable to the pivotal study. Clinical trial information: NCT03013335.
Cytoreductive nephrectomy in metastatic papillary renal cell carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC).
Authors: Graham Jeffrey , Wells Connor , Donskov Frede , Lee Jae-Lyun , Fraccon Anna Paola , Pasini Felice , Porta Camillo , Bowman I. Alex , Bjarnason Georg A. , Ernst D. Scott , Rha Sun Young , Beuselinck Benoit , Hansen Aaron Richard , North Scott A. , Kollmannsberger Christian K. , Wood Lori , Vaishampayan Ulka N. , Pal Sumanta K. , Choueiri Toni K. , Heng Daniel Yick Chin 
Published: February 2018

581 Background: There is evidence that cytoreductive nephrectomy (CN) may be beneficial in metastatic renal cell carcinoma (mRCC), but the role of CN in patients with papillary histology is unclear. Methods: Using the IMDC database, a retrospective analysis was performed on patients with papillary mRCC treated with or without CN. Baseline characteristics and IMDC risk factors were collected. Median overall survival (OS) was determined for both patient groups. Multivariable Cox regression analysis was performed to control for imbalances in individual IMDC risk factors. Results: In total, 353 patients with papillary mRCC with (n = 75) or without (n = 278) a component of clear cell histology were identified. Median follow-up time was 57.1 months (95% CI 32.9-77.8) and the OS from the start of first-line targeted therapy for the entire cohort was 13.2 months (95% CI 12.0-16.1). Baseline characteristics are in Table 1 and patients who had CN were more likely to be younger, with better KPS, and have sarcomatoid histology. Median OS in patients with CN was 16.3 months (95% CI 13.1-19.2), compared to 8.6 months (95% CI 6.1-12.2; p < 0.0001) in the no CN group. When adjusted for individual IMDC risk factors, the hazard ratio (HR) of death for CN was 0.62 (95% CI 0.45-0.85; p = 0.0031). Conclusions: The use of CN in patients with mRCC and papillary histology appears to be associated with improved survival when compared to no CN after adjustment for risk criteria. A clinical trial in this rare population may not be possible but this data does corroborate with clear cell literature. [Table: see text]
Utilization and survival implications of a delayed approach to targeted therapy for metastatic renal cell carcinoma: A nationwide cancer registry study.
Authors: Woldu Solomon L. , Matulay Justin T. , Clinton Timothy N , Singla Nirmish , Freifeld Yuval N , Sanli Oner N , Krabbe Laura-Maria , Hutchinson Ryan C , Lotan Yair , Hammers Hans J. , Hannan Raquibul , Brugarolas James , Bagrodia Aditya , Margulis Vitaly 
Published: February 2018

586 Background: Targeted therapy (TT) is the first-line option for metastatic renal cell carcinoma (mRCC) however, it is not curative and associated with a high-cost and adverse events. Preliminary data suggests TT may be safely delayed in appropriately selected patient, however the utilization and impact of delayed TT has not been evaluated on larger-scale. Methods: The National Cancer Database (NCDB) was queried from 2006-2012 for patients with mRCC treated with cytoreductive nephrectomy and TT. Time to initiation of TT was defined as ‘early’ (within 2 months), ‘moderately delayed’ (2-4 months), and ‘delayed’ (4-6 months), and ‘late’ ( > 6 months) based on time from diagnosis to initiation of therapy. Multivariable logistic regression was performed to determine factors associated with delayed TT. The impact time to initiation of TT on OS was estimated by Kaplan-Meier and Cox multivariable survival analysis. Results: For2,716 patients in the analysis, the median (interquartile range [IQR]) follow-up was 18.8 (9.1-32.9) months, and 71.8% of patients had died at last follow-up. The median (IQR) time from diagnosis to initiation of TT was 2.1 (1.3-3.23) months, with the longest delay being 20.1 months. 1,255 patients (46.2%) had early TT, 1,072 patients (39.5%) had moderately delayed TT, 284 patients (10.5%) had delayed TT, and 105 patients (3.9%) had late TT. Delay in TT was not found to be a predictor of mortality in multivariable analysis; early TT (reference), moderately delayed TT (HR 0.98, p = 0.74), delayed TT (HR 0.95, p = 0.51), and late TT (HR 0.86, p = 0.20). Time from diagnosis to initiation of TT and time from initiation of TT to patient death were not correlated after control for covariates ( r= 0.04, p = 0.08). Conclusions: Delay in initiation of TT for mRCC was not an independent predictor of worse OS. Although this study is subject to limitations of observation study design and selection bias, the results are consistent with the notion that in carefully selected patients, outcomes might not be compromised with initial observation. Prospective, randomized evaluation is warranted.
Impact of metastatic local treatment in the strategy of metastatic renal cell carinoma including sterotactic radiotherapy, surgery, and radiofrequency in an expert center.
Authors: Salabert Laura , Gross-Goupil Marine , Haaser Thibaud , Bernhard Jean-Christophe , Palussière Jean , Ravaud Alain 
Published: February 2018

596 Background: Standard treatment of metastatic renal clear cell carcinoma is based upon nephrectomy, and systemic treatment with targeted agents. These drugs induce frequent side effects that may compromise observance and quality of life. Considering a focal treatment of one or more metastases can lead to a drug-holidays, or allow to postpone systemic treatment start in oligometastatic disease. Such focal treatment techniques are surgery, radiofrequency ablation (RFA) or stereotactic radiotherapy (SRT). Methods: In this retrospective, monocentric and analytic study, we analyzed progression-free survival (PFS) and overall survival (OS) after a focal treatment in a cohort of patients from Bordeaux University Hospital, involving similar staff members along time. We have also reported local control, complications and potential predictive factors associated with a better outcome. Results: Seventy-one patients with 78 focal treatments (23 RFA, 47 metastasectomy and 8 SRT) have been included in our study. For 44 patients, the disease was oligometastatic, (1 to sites, less than 5 metastases) including 15 patients with a partial response to systemic treatment before the focal approach, and 12 patients with a dissociated response to systemic treatment. Progression post focal treatment occurred in 53 (74.6 %) of patients. Median PFS was 14 months (95 % confidence interval [CI], - 8-16 months); and median OS was 77 months (95 % CI, 41 months-not reach). Local control rate was 83.3 %, and complication rate was 36.3 % due to local treatments, without death related to iatrogenic events. A diagnosis of metachrone metastases and a disease-free interval between the first diagnosis and the occurrence of the metastases of at least one year seemed to be associated with better outcomes. Conclusions: Data observed in our study are consistent with those reported in literature. The prolonged OS and PFS post focal treatment should encourage clinical oncologists to discuss this multimodal approach (association of systemic and focal treatments). This approach should be also evaluated in the context of the immunocheckpoint inhibitor in the future.
The perineural invasion paradox: Is perineural invasion an independent prognostic indicator of biochemical recurrence risk in patients with pT2N0 prostate cancer?
Authors: Kraus Ryan , Cheng Nathan , Ji Lingyun , Jennelle Richard Lester Stephen , Groshen Susan G. , Ballas Leslie 
Published: February 2018

6 Background: Perineural invasion is a histologic feature present in approximately 19% of patients with prostate cancer. The prognostic significance of perineural invasion is controversial with recent studies yielding contradictory results. This study aims to assess whether perineural invasion on surgical pathology of patients with pT2N0 disease is an independent prognostic indicator of the risk of biochemical recurrence. Methods: We identified 201 patients with non-metastatic pT2N0 prostate cancer at our institution between 1/1/2008-12/31/2014. We reviewed the electronic medical record of these patients and identified whether the patient had biochemical recurrence (defined as PSA > 0.2 after surgery). A multivariable analysis was then performed using clinical and histological data for each patient to assess the association between perineural invasion and biochemical recurrence. Results: Of the 201 patients identified, 68.1% (137/201) had perineural invasion and 14% (28/201) had biochemical recurrence. Perineural invasion was associated with pT2c disease (p < 0.001), an increased number of positive cores on biopsy (p < 0.001), and a higher surgical Gleason score (p < 0.001). 19% of patients with perineural invasion had disease recurrence compared to 3.1% without perineural invasion (p = 0.001, Hazard ratio of 6.2). After performing a multivariable analysis and accounting for pathologic tumor staging and Gleason score, perineural invasion had a trend towards a significant association with recurrence (p = 0.085, Hazard ratio of 3.2). Conclusions: Perineural invasion may be an indicator of unfavorable histology such as a high Gleason score or more widespread disease rather than an independent prognostic indicator of the risk of biochemical recurrence.
Improved survival rates in kidney cancer patients with brain metastases treated with modern multidisciplinary approaches.
Authors: Bowman I. Alex , Bent Alisha , Le Tri , Christie Alana , Wardak Zabi , Mickey Bruce , Timmerman Robert D. , Hannan Raquibul , Brugarolas James 
Published: February 2018

601 Background: Brain metastases (BM) in RCC have been associated with poor overall survival. Systemic targeted and immunotherapy and the increasing use of stereotactic radiosurgery (SRS) is likely to improve outcomes. Methods: A retrospective database of mRCC patients treated at our institution between 2006 and 2015 was compiled and patients with BM identified. Overall survival (OS) was analyzed by the Kaplan-Meier method. BM patients were compared to non-BM patients after adjusting for the timing of BM diagnosis, either prior to or during 1st line systemic therapy (ST). Results: 56 of 248 mRCC patients (22.6%) were diagnosed with BM, 35 (62.5%) prior to and 21 (37.5%) during 1st line ST. 43/56 (77%) received definitive local therapy for BM (surgery 10, SRS 26, or both 7). 9 received WBRT only and 4 had no CNS-directed therapy. All patients received ST. The median OS for ST-naïve BM patients compared with non-BM patients was 19.5 vs. 28.7 months (p = 0.012). Survival for patients developing BM on 1st-line therapy was not significantly different from patients without BM progressing on 1st line ST (11.8 vs. 17.8 months, p = 0.66). BM patients with poor risk mRCC by IMDC criteria did worse than those without BM regardless of line of therapy. Conclusions: Survival for patients with BM and favorable or intermediate risk mRCC is significantly better than historical reports and similar to non-BM patients in our population which was heavily treated with both systemic and local therapies. Patients with BM and poor risk RCC had significantly worse survival, suggesting that risk group should be considered when counseling on prognosis and selecting treatment. [Table: see text]
Prognostic and predictive role of fumarate hydratase in metastatic clear cell renal cell carcinoma.
Authors: Vernieri Claudio , Fucà Giovanni , Massa Simona , Ratta Raffaele , Verzoni Elena , Grassi Paolo , Calareso Giuseppina , Pruneri Giancarlo , Minucci Saverio , de Braud Filippo , Colecchia Maurizio , Procopio Giuseppe 
Published: February 2018

617 Background: Metabolic disruption is frequent in renal cell carcinoma (RCC). Loss of the mitochondrial fumarate hydratase (FH) enzyme is associated with enhanced glycolytic metabolism, angiogenesis and clinical aggressiveness in type 2 papillary RCC. However, FH expression has never been evaluated in clear cell RCC (ccRCC). In this study, we investigated the impact of FH expression on the outcomes of patients (pts) with metastatic ccRCC (mccRCC). Methods: We included pts with mccRCC, for whom formalin-fixed, paraffin embedded (FFPE) tissue from the primary tumor had been obtained before initiation of systemic treatment. FH levels were evaluated by immunohistochemistry (IHC), and were defined as “normal” if FH expression in most cancer cells was comparable to the adjacent normal tubular cells and “low” in the opposite case. We evaluated the association between FH levels and clinico-pathological characteristics through the chi-squared or Fisher’s exact test. The log-rank test was used to compare survival between patient subgroups. Results: We evaluated 49 mccRCC pts, of whom 36 (73.5%) had synchronous metastases. FH levels were normal in 29 (59.2%) pts and low in 20 (40.8%) pts. FH expression was not associated with patient age (p = 0.5), sex (p = 0.34), tumor grade (p = 0.66), T stage (p = 0.38), N stage (p = 0.88), metastatic disease at the time of diagnosis (p = 0.4), number of metastatic sites (p = 1) or sarcomatoid morphology (p = 0.36). 44 pts received first-line therapy with tyrosine kinase inhibitors (TKIs). In pts with low as compared to normal FH levels, median progression free survival (mPFS) during any first-line treatment was 34 and 10.1 months, respectively (HR 0.39, 95% CI 0.18-0.85; p = 0.014), while mPFS during first-line TKI therapy was 34 and 8.42 months, respectively (HR 0.4, 95% CI 0.17-0.94; p = 0.03). Median overall survival (OS) was not reached in pts with FH-low tumors, while it was 22.9 months in normally expressing ones (HR 0.14, 95% CI 0.032-0.63; p = 0.028). Conclusions: In mccRCC pts, low FH expression in primary tumors is associated with longer PFS during any first-line or TKI treatment, and also with better OS. This is the first study to reveal a prognostic and predictive role of FH levels in mccRCC.
The EVERPRO study: Final results of a non-interventional study (NIS) evaluating the quality of life (QoL) in second-line treatment of metastatic renal cell carcinoma (mRCC) with everolimus.
Authors: Goebell Peter-Juergen , Herrmann Edwin , Kube Ulrich , Doehn Christian , Marschner Norbert Walter , Dietel Anja , Blumenstengel Klaus , Grimm Marc-Oliver , Scheffler Michael Thomas , Rogler Anja , Bergmann Lothar 
Published: February 2018

631 The EVERPRO study: Final results of a non-interventional study evaluating QoL in second-line treatment of mRCC with everolimus Background: Although the prognosis of mRCC patients remains poor, median overall survival has improved since 2006, probably due to the introduction of TKIs. Everolimus treatment following first-line VEGFR-TKI was demonstrated to be efficacious and safe and is recommended by current guidelines. Assuring an adequate QoL has become a major therapy goal, especially in the 2nd line. Hence, QoL and the implication of time effort of everolimus treatment were the major objectives assessed in this study. Methods: Adult patients scheduled for in-label everolimus treatment after 1st line VEGFR-TKI or bevacizumab were eligible. QoL was assessed by means of the NCCN-FACT FKSI-19 questionnaire. Additionally, time needed for therapy and limitations thereof were evaluated based on a particularly developed questionnaire (including total treatment duration and treatment type). Results: 202 patients were evaluable for analyses. Median treatment duration was 19.1 weeks [95% CI: 16.4 – 23.0] and median time to progression was 26.0 weeks [95% CI: 23.3 – 32.6]. The FKSI-19 median total score remained stable during treatment. The median time effort spent on total therapy was 20 hours per patient. Most of the patients stated to have ‘no’, ‘a little’ or ‘moderate’ limitations in their daily, social and professional life. Two months after treatment start, 65 patients reported none or a little time burden due to therapy. 167 patients experienced 804 adverse events (AEs) in total. The most commonly reported AEs related to everolimus were dyspnoea, fatigue and anaemia (all grade). Conclusions: QoL was maintained during everolimus therapy and limitations as well as time effort were acceptable for most patients. The observed safety profile is consistent with previous data and does not implicate changes on the benefit-risk balance of everolimus. This study supports previously published data demonstrating that everolimus is an effective and safe treatment option following a VEGF(R)-targeted drug. Clinical trial information: 2284.