bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient-reported psychosocial distress in adolescents and young adults with germ cell tumors.
Authors: Soleimani Maryam , Ho Cheryl , Kollmannsberger Christian K. , Bates Alan , Leung Bonnie 
Published: March 2019

521 Background: Germ cell tumours are the most common cancer of male adolescents and young adults (AYA, age 18-39). Men in this age group have been healthy much of their lives, and are at a stage of personal and professional growth, consequently a diagnosis of cancer can cause significant psychosocial distress. We evaluated patient reported psychosocial distress and hypothesized that AYA compared to older patients experienced more anxiety and distress in emotional, practical and physical domains. Methods: All patients referred to BC Cancer complete the Psychosocial Screen for Cancer (PSSCAN-R) at first consultation. This is a validated screening questionnaire for distress. Components include a screen for subclinical/clinical symptoms of depression and anxiety and the Canadian Problem Checklist (CPC) with 6 domains of concern: emotional, informational, practical, spiritual, social/family and physical. Results: Data was collected for 349 patients from 2011-2015. Baseline characteristics: 227 (65%) AYA, median age 33 (range 18-83), 41 (11%) metastatic disease at diagnosis. The top 3 AYA concerns were work/school (38.3%), financial (34.8%), frustration and anger (26%). AYA patients scored positive for subclinical/clinical anxiety more commonly than their older counterparts (39.4% vs. 27.9%, p = 0.028). AYA patients with subclinical/clinical anxiety symptoms experienced more fears and worries (41.5%), concerns regarding work/school (38%), lack of understanding of their disease (37.9%), finances (35.3%) and frustration and anger (26.3%) than AYA patients who do not express anxiety symptoms. Conclusions: The results of this study indicate that AYA with testicular cancer have unique needs and experience significantly more self-reported anxiety symptoms with emotional, informational, and practical concerns. Programs tailored to address needs of AYA patients may help reduce anxiety and improve the cancer experience. The results of this study are valuable to stakeholders for allocation of resources to address psychosocial parameters of distress in this patient group.
Survival and toxicity outcomes in patients age 40 or older with relapsed metastatic germ cell tumors (mGCT) treated with high-dose chemotherapy (HDCT) and autologous peripheral-blood stem cell transplant (PBSCT).
Authors: Adra Nabil , Albany Costantine , Abonour Rafat , Abu Zaid Mohammad Issam , Pereira Dannillo , Althouse Sandra K. , Sullivan Cheryl K , Hanna Nasser H. , Einhorn Lawrence H. 
Published: March 2019

522 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity which can be more pronounced in older patients. We report survival and toxicity outcomes in pts with relapsed mGCT age ≥ 40 at time of HDCT. Methods: 440 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University (IU) between 2004-2017 per our previous reported regimen (N Engl J Med 2007; 357: 340-8). Kaplan-Meier methods were used for progression free survival (PFS) analysis. Results: 110 pts were age ≥ 40 while 330 pts were age < 40. Among pts age ≥ 40, median AFP was 6.6 (range, 1-2,709) and median hCG was 5.3 (range, 1-42, 453). Of the 110 pts age ≥ 40, 75 had complete remission without relapse during a median follow-up of 23 months. There were 3 treatment-related deaths. Conclusions: HDCT plus PBSCT is safe and effective salvage therapy in pts age ≥ 40 with relapsed mGCT. [Table: see text]
Genomic features of metastatic testicular sex cord stromal tumors.
Authors: Necchi Andrea , Bratslavsky Gennady , Pinkhasov Rubin , Shapiro Oleg , Gay Laurie M. , Elvin Julia Andrea , Vergilio Jo-Anne , Killian Jonathan Keith , Nho Nhu Thi , Ramkissoon Shakti , Severson Eric Allan , Hemmerich Amanda , Ali Siraj Mahamed , Chung Jon , Reddy Venkataprasanth P. , Miller Vincent A. , Schrock Alexa Betzig , Ross Jeffrey S. , Liu Nick , Jacob Joseph 
Published: March 2019

532 Background: Metastatic testicular sex cord stromal tumors of the testis (MSCST) comprise an extremely uncommon form of genitourinary malignancy. In a comparative genomic study, we performed comprehensive genomic profiling (CGP) to characterize the genomic alterations (GA) in MSCST and to enable the search for potential therapy targets. Methods: The MSCST were classified as metastatic Leydig Cell Tumors (LCT), Sertoli Cell Tumors (SCT) and Undifferentiated (USCST). In this study, 10 cases of LCT, 6 cases of SCT and 3 cases of USCST underwent hybrid-capture based CGP to evaluate all classes of genomic alterations. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. Results: All patients had clinically advanced recurrent and/or metastatic disease. The primary testis tumor was used for sequencing in 6 MSCST (32%) and a metastatic site in 9 (68%) of the MSCST. In 10 (91%) of 11 MSCST positively stained by IHC for inhibin expression. The overall frequencies of GA were similar in all LCT, SCT and UTST ranging from 3.0 to 3.5 GA/tumor. The most frequent untargetable GA found in all MSCST cases included CTNNB1 and CDKN2A/B, both ranging from 20-33% of cases. Targetable GA were uncommon in all MSCST sub-groups but several tumors featured potential for cell cycle inhibitors ( CDK4 in LCT), MTOR inhibitors ( RICTOR, NF2 and PTEN in all 3 tumor types), hedgehog inhibitors ( PTCH1 in LCT) and PARP inhibitors ( BAP1 in SCT). No MSI-High status was identified in any MSCST. The TMB was also low in all MSCST groups. Conclusions: Although the 3 subgroups of testicular MSCST feature defining histopathologic features, these tumors have similar genomic signatures on CGP. The low levels of GA per tumor, infrequent tumor aneuploidy, absence of MSI-High status and low TMB all indicate that testicular MSCST are genetically stable. However, rare cases of testicular MSCST reveal GA linked to potential targeted therapy benefits on CGP linked to dysregulation of multiple biologic pathways. In contrast, the lack of MSI-High status and overall low TMB in testicular MSCST indicates a likely lack of benefit for immunotherapies for these rare forms of malignancy.
Safety and efficacy of nivolumab in metastatic renal cell carcinoma (mRCC): Final analysis from the NIVOREN GETUG AFU 26 study.
Authors: Albiges Laurence , Negrier Sylvie , Dalban Cécile , Chevreau Christine , Gravis Gwenaelle , Oudard Stephane , Laguerre Brigitte , Barthelemy Philippe , Borchiellini Delphine , Gross-Goupil Marine , Geoffrois Lionnel , Rolland Frederic , Thiery-Vuillemin Antoine , Joly Florence , Ladoire Sylvain , Tantot Florence , Escudier Bernard ,   GETUG
Published: March 2019

542 Background: NIVOREN GETUG AFU 26 study, is a French multicenter prospective study to evaluate safety and efficacy of Nivolumab (N) in a broad “real world setting” in mRCC after failure of 1 or 2 tyrosine kinase inhibitors. Methods: Between February 2016 and June 2017, 729 pts have been enrolled across 27 institutions. Primary objective of the trial was safety assessed by grade ≥ 3 treatment related adverse event (TRAE). Results: Overall, 720 patients treated with N were included in this final analysis. All pts had clear cell mRCC. Median age was 64 years old, 77.4% were male, 84.7% had prior nephrectomy. ECOG PS was >1 in 15.0%, 21.3% pts had received prior everolimus, 22.4% pts had received more than 2 previous lines, IMDC risk groups were 18.3%/56.2%/25.5% for good/intermediate and poor risk respectively. Brain Metastasis at screening was noted in 83 (12.3%) pts. With a median follow up of 20.9 months (mo), median duration of treatment was 5.2 mo (0.5; 28.1) with 15% of pts still on therapy. Median PFS was 3.2 IC 95% [2.9; 4.6] mo. At the time of this analysis, 316 pts have died and 12 mo OS rate was 69% IC 95% [66; 73]. Objective response rate was 20.8% (1.2% CR, 19.6%PR). Stable disease was seen in 31.6% and PD in 47.6%. Noteworthy, 46.1% of pts were treated beyond progression. Overall, 123 pts (17.1%) have presented at least one grade ≥ 3 TRAE, including asthenia (2.4%), metabolic disorders (2.1%), gastro-intestinal disorders (1 .9%), musculoskeletal (1.7%), renal disorders (1.3%), hematologic (1.3%). 6 patients have developed grade 5 toxicity (2 cardiac failure, 1 macrophage activation syndrom, 1 Cerebral hemorrhage, 1 unknown). Treatment discontinuation due to any grade TRAE occurred in 54 pts (7.5%). Interestingly, pts with grade ≥ 3 TRAE had longer PFS than pts without grade ≥ 3 TRAE (HR 0.69 [0.55-0.87]). Conclusions: We report the primary objective 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 similar to the pivotal study. Grade ≥ 3 TRAE was associated with longer PFS. Clinical trial information: NCT03013335.
Subgroup analysis from JAVELIN Renal 101: Outcomes for avelumab plus axitinib (A + Ax) versus sunitinib (S) in advanced renal cell carcinoma (aRCC).
Authors: Choueiri Toni K. , Motzer Robert J. , Campbell Matthew T. , Alekseev Boris Y. , Uemura Motohide , Kollmannsberger Christian K. , Gravis Gwenaelle , Bjarnason Georg A. , Gurney Howard , Chung Jinsoo , Haanen John B. A. G. , Rini Brian I. , Larkin James M. G. , Schmidinger Manuela , Nole Franco , Chudnovsky Aleksander , Huang Bo , Hariharan Subramanian , di Pietro Alessandra , Albiges Laurence 
Published: March 2019

544 Background: In the ongoing phase 3 JAVELIN Renal 101 trial, progression-free survival (PFS) was longer (median, 13.8 vs 8.4 mo; hazard ratio, 0.69; p=0.0001) and the objective response rate (ORR) was higher (51% vs 26%) with A + Ax vs S in patients with previously untreated aRCC. Here we report outcomes from an analysis of several prespecified subgroups. Methods: Patients were randomized 1:1 to receive A (10 mg/kg) IV every 2 weeks + Ax (5 mg) PO twice daily or S (50 mg) PO once daily for 4 wk (6-wk cycle). Primary and key secondary endpoints were PFS per independent review committee (IRC; RECIST v1.1) and OS in patients with PD-L1+ tumors (≥1% of immune cells) and in patients irrespective of PD-L1 expression; other secondary endpoints included OR per IRC (RECIST v1.1). Results: A total of 886 patients were randomized; 560 (63%) had PD-L1+ tumors. At data cut-off (Jun 2018), median follow-up was 12.0 vs 11.5 mo for A + Ax vs S groups. The table shows PFS and ORR by MSKCC and IMDC risk groups (F, favorable; I, intermediate; P, poor) and PD-L1 subgroup. Similar results for prognostic risk were seen in patients with PD-L1+ tumors. Outcome data (including PFS2) for additional clinical subgroups by baseline demographics and features will be presented. Clinical trial information: NCT02684006. Conclusions: A + Ax demonstrated PFS and OR benefit across all prognostic risk groups and PD-L1 subgroups vs S in aRCC.[Table: see text]
Thirty-month follow-up of the phase III CheckMate 214 trial of first-line nivolumab + ipilimumab (N+I) or sunitinib (S) in patients (pts) with advanced renal cell carcinoma (aRCC).
Authors: Tannir Nizar M. , Frontera Osvaldo Arén , Hammers Hans J. , Carducci Michael Anthony , McDermott David F. , Salman Pamela , Escudier Bernard , Beuselinck Benoit , Amin Asim , Porta Camillo , George Saby , Bracarda Sergio , Tykodi Scott S. , Powles Thomas , Rini Brian I. , Tomita Yoshihiko , McHenry M. Brent , Mekan Sabeen Fatima , Motzer Robert J. 
Published: March 2019

547 Background: N+I showed superior OS v S in ITT (IMDC any risk) and intermediate/poor-risk (I/P) pts with aRCC in CheckMate 214 at 17.5 mo min follow-up. Methods: Pts with clear cell aRCC were randomized 1:1 to N3 mg/kg + I1 mg/kg Q3W×4 and then N3 mg/kg Q2W, or S 50 mg daily for 4 wk on, 2 wk off. Co-primary endpoints were OS, RECISTv1.1 ORR and PFS per IRRC in I/P pts. PFS and ORR were assessed by investigator (inv) at 30 mo. Results: At 30 mo min follow-up, OS remains significantly improved in ITT and I/P pts with N+I v S; the HR for OS in favorable (fav) risk pts has improved for N+I v the previous analysis (1.22 [95% CI 0.73–2.04] v 1.45 [99.8% CI 0.51‒4.12]). Per previous IRRC ORR (N+I, 42% [95% CI 37‒47]; S, 27% [95% CI 22‒31]), ORR per inv was higher with N+I v S in ITT and I/P pts. ORR CIs overlapped in fav pts, CR was doubled with N+I v S. Increasing PFS benefit with N+I v S is emerging in ITT and I/P pts; PFS CIs between arms remain overlapping in fav pts (Table). 15% v 9% of N+I and S ITT pts remain on therapy, and 48% v 61% have received 2nd-line systemic therapy; 39% of S pts received subsequent immune-checkpoint inhibitor therapy. Among pts who were alive with CR, 50% v 10% remain on treatment with N+I (n = 56) v S (n = 10). 5 N+I and 7 S additional pts developed Gr 3–4 drug-related AEs; 1 N+I and 3 S additional pts had AEs leading to discontinuation. No new drug-related deaths occurred. Conclusions: At 30 mo min follow-up, OS and ORR remain improved with N+I v S in ITT and I/P CheckMate 214 pts. No new safety signals emerged with longer follow-up. Clinical trial information: NCT02231749. [Table: see text]
Genomic analysis of mitochondrial mutations in chromophobe renal cell carcinoma by using low-depth whole genome sequencing.
Authors: Kang Minyong , Shin Yong Ho , Joung Jae Young , Seo Seong Il 
Published: March 2019

553 Background: Mitochondria have a circular genome that is independent of the nuclear genome of the nucleus. Mutations of mitochondrial DNA rarely occur during tumorigenesis. Chromophobe renal cell carcinoma (chRCCC) is a type of kidney tumor characterized by a morphologic abnormality of mitochondria. However, there is still little research on the existence of mitochondrial mutation in chRCC and how it plays a role in tumorigenesis. Here, we investigated the mutation patterns of mitochondria genome in chRCC using low-depth sequencing technique. Methods: We evaluated 17 patients with chRCC who underwent radical nephrectomy from December 2010 to January 2017. Mitochondrial genomic analysis was performed by low-depth sequencing. Varscan and MToolBox analysis programs were used to search for mutations. Germline mutation information reported in MtDB, Phylotree, and Mitomap databases was used to allocate patient haplogroups and exclude germline mutations. Results: Whole genome sequencing of 17 chRCC tissues at an average depth of 1x based on whole genome revealed that the mitochondrial genome was sequenced to an average of 630x. A total of 1,206 Haplotype frequency > 0.25 mutations were found, of which 30 were mutations not reported in the database. Seven of them were identified as synonymous mutations (average of 0.41 and 41% per tumor), and three were truncating mutations (average of 0.18 per tumor; 18%). Truncating mutations were specifically identified as two frameshift indel and one stop gain mutation. Conclusions: In summary, our study showed that the frequency of truncating mutation of mitochondrial DNA was higher in chRCC compared to other solid tumors which have a low frequency of 1-2%. This finding suggests that dysfunctional mitochondria may play an oncogenic role in tumorigenesis of chRCC, while other tumors are predicted to undergo negative selection of mitochondrial truncating mutations during tumorigenesis. Based on these results, we are performing prospective study for evaluating mutational characteristics and associated morphological changes of mitochondria under electron microscopy.
Thick perirenal fat predicts the growth pattern of renal cell carcinoma.
Authors: Kashiwagi Eiji , Imada Kenjiro , Shiota Masaki , Takeuchi Ario , Inokuchi Junichi , Tatsugami Katsunori , Eto Masatoshi 
Published: March 2019

554 Background: Partial nephrectomy is the standard surgical treatment for T1a renal cell carcinoma (RCC) and select T1b. Among these tumor classes, the tumor location can be divided into inner or outer. However, little attention has been paid to the mechanism of the pattern of RCC growth. In our body, there are two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is important for energy storage and BAT is important for thermogenesis. BAT expresses uncoupling protein 1 (UCP-1), and mainly located in mediastinal, supraclavicular and perirenal tissues. But no studies have been done to investigate the relationship between RCC and BAT.In this study, we examined the association between adipose tissue, especially around kidney, and the growth pattern of RCC. Methods: We retrospectively reviewed computed tomography scans of 153 patients with stage 1 RCC who underwent radical or partial nephrectomy in our hospital between January 2013 and July 2016. We calculated the visceral/subcutaneous/perirenal fat volumes using SYNAPSE VINCENT. Of the 60 patients, the perirenal fat was immunohistochemically stained for leptin, adiponectin, COX-2 and UCP-1, and the association with outward tumor protrusion was evaluated. Results: Of the 153 cases, 88 had confirmed outward expansion (57.5%), 110 were classed as pT1a (52 and 58 with outer and inner expansion, respectively), 43 were classed as pT1b (36 and 7 with outer and inner expansion, respectively; P < 0.0001). Multivariate Cox model showed a trend toward significance in pT1b (vs. pT1a, OR 6.033, 95% CI = 2.409-15.108, P = 0.0001), perirenal fat percentage > 1.0 (vs. ≤ 1.0, OR 2.596, 95% CI = 1.205-5.591, P = 0.014). as independent predictors for outer protrusion. Immunohistochemical staining was positive for UCP-1 expression in 31 out of 41 outgrowth types (75.6%), and all 19 endogenous types (100%; P = 0.003). Conclusions: Renal cell carcinoma with thick perirenal fat correlates with an increased likelihood of developing outward tumor protrusion; therefore, fat distribution and UCP1 expression may affect the development of renal cell carcinoma.
Sporadic angiomyolipomas (AMLs) growth kinetics while on everolimus (SAGE).
Authors: Geynisman Daniel M. , Kadow Brian T. , Shuch Brian M. , Boorjian Stephen A. , Matin Surena F. , Rampersaud Edward , McClean Daniel , Milestone Barton N , Plimack Elizabeth R. , Zibelman Matthew R. , Kutikov Alexander , Smaldone Marc C. , Chen David , Viterbo Rosalia , Joshi Shreyas , Greenberg Richard E. , Malizzia Lois , McGowan Thomas , Ross Eric A. , Uzzo Robert 
Published: March 2019

560 Background: Level I evidence exists demonstrating the efficacy of the mTOR inhibitor everolimus (EVE) in decreasing tumor volume of syndromic angiomyolipomas (AMLs) among patients with Tuberous Sclerosis. No prospective data are available regarding the effect of mTOR inhibition on growth kinetics in patients with sporadic AMLs. Methods: We conducted a multi-institutional, prospective, phase 2 trial with an optimal two-stage Simon design in patients presenting with > 3cm sporadic AMLs who were candidates for surgical or percutaneous intervention. Response was defined as ≥25% volumetric reduction of the AML. Planned enrollment was 43 patients to test the null hypothesis at a 5% level of significance with 80% power. Baseline, 4- and 6-month volumetric analysis was performed by dynamic contrast-enhanced MRI (DCE-MRI). Patients received EVE 10mg for four 28-day cycles, at which point EVE was discontinued in those with < 25% volumetric reduction. Those with ≥ 25% volumetric reduction received two additional cycles of EVE. Dose reductions and interruptions were allowed to 5 mg QOD. Conservative stopping rules were established for toxicity, given the benign nature of AMLs. Results: The early stopping rules for both efficacy and toxicity were invoked. We enrolled 20 patients (median age = 68) from 5 centers with 21 sporadic AMLs. 11/20 (55%) patients completed 4 cycles of EVE, while 7/20 (35%) completed 6 cycles. Median days on treatment was 88 (2 cycles). 4/20 (20%) patients were withdrawn due to toxicity, while 8/20 (40%) withdrew due to personal preference. Dose reductions were required in 6/20 (30%) patients, and 5/20 (25%) patients had grade 3 toxicities which resolved upon discontinuation or dose reduction of EVE. At 4-month MRI, 10/16 (62.5%) patients had a ≥25% reduction in volume (mean = 54.1% decrease). At 6-month MRI, 8/12 (66.6%) patients had a ≥25% reduction in volume (mean = 51.5% decrease). Conclusions: EVE was effective in reducing tumor volume in patients with sporadic AMLs but was associated with a high rate of treatment termination due to patient preference or prespecified AEs. Neoadjuvant EVE may be useful in potentiating surgical resection of large or anatomically complex AMLs. Clinical trial information: NCT02539459.
Treatment-free survival (TFS) after discontinuation of first-line nivolumab (NIVO) plus ipilimumab (IPI) or sunitinib (SUN) in intention-to-treat (ITT) and IMDC favorable-risk patients (pts) with advanced renal cell carcinoma (aRCC) from CheckMate 214.
Authors: McDermott David F. , Rini Brian I. , Motzer Robert J. , Tannir Nizar M. , Escudier Bernard , Kollmannsberger Christian K. , Hammers Hans J. , Porta Camillo , George Saby , Donskov Frede , Gurney Howard , Grimm Marc-Oliver , Harrison Michael Roger , Hutson Thomas E. , Yang Shuo , Johansen Jennifer , Rao Sumati , Mekan Sabeen Fatima , Rael Michael , Powles Thomas 
Published: March 2019

564 Background: TFS characterizes the antitumor activity of immuno-oncology agents after treatment discontinuation. In CheckMate 214, pts with IMDC intermediate/poor-risk aRCC who discontinued first-line NIVO+IPI experienced significantly longer TFS than those who discontinued SUN (McDermott et al, ESMO 2018). Here, we continue the analysis of TFS from CheckMate 214 in ITT and IMDC favorable-risk pts. Methods: Pts with previously untreated, predominantly clear cell aRCC were randomized 1:1 to intravenous NIVO 3 mg/kg + IPI 1 mg/kg every 3 weeks for 4 doses followed by NIVO 3 mg/kg every 2 weeks, or oral SUN 50 mg daily for 4 weeks on, 2 weeks off (6-week cycles). TFS was defined as the time from protocol therapy cessation to the start of subsequent systemic anticancer therapy or death, whichever occurred first. TFS in pts who discontinued NIVO+IPI or SUN was compared using Kaplan–Meier methods and log-rank tests. This analysis was conducted for all ITT (NIVO+IPI, 550; SUN, 546) and IMDC favorable-risk (NIVO+IPI, 125; SUN, 124) pts in CheckMate 214. Results: Among 463 NIVO+IPI and 477 SUN ITT pts who discontinued protocol therapy, the median TFS was 3.0 months with NIVO+IPI vs 1.3 months with SUN (HR [95% CI]; 0.54 [0.46–0.62]; P<0.0001); the TFS rates 2 years post-discontinuation were 21% vs 7%, respectively. In IMDC favorable-risk pts, 111 and 94 pts discontinued from NIVO+IPI and SUN, respectively. TFS in IMDC favorable-risk pts was also significantly longer with NIVO+IPI vs SUN (median, 6.3 vs 1.1 months; HR [95% CI]; 0.47 [0.34–0.65]; P<0.0001). The TFS rates 2 years post-discontinuation in favorable-risk pts were 29% for NIVO+IPI vs 13% for SUN. Conclusions: Similar to the TFS benefit seen in intermediate/poor-risk pts with aRCC, first-line therapy with NIVO+IPI resulted in reduced need for second-line therapy in ITT and IMDC favorable-risk pts compared with SUN. The durable TFS benefit across risk groups despite discontinuation of therapy provides further evidence of the encouraging benefit-risk profile of NIVO+IPI over SUN in pts with previously untreated aRCC. Clinical trial information: NCT02231749.