bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of cytoreductive nephrectomy (CN) on survival in metastatic renal cell cancer (mRCC) treated with immune checkpoint inhibitors (ICI).
Authors: Perimbeti Stuthi , Jiang Changchuan , Deng Lei , Roy Arya , Gopalakrishnan Keerthy , Chatta Gurkamal S. , George Saby , Gopalakrishnan Dharmesh 
Published: February 2022

359 Background: The advent of ICIs has dramatically changed the treatment paradigm in mRCC. Although CN was demonstrated to improve survival in combination with cytokine-based therapies, its role is not well-defined in the ICI era. We aimed to compare survival outcomes of patients treated with ICIs, based on their CN status. Methods: The National Cancer Database was queried to identify all patients older than 18 years with mRCC who received ICIs from 2015 to 2018. Chi-Square and Mann-Whitney U tests were used to compare frequency distributions. Cox proportional hazards regression was employed for multivariate analysis of factors associated with overall survival (OS). Results: A total of 4,369 patients were identified- 36.4% (n=1589) had undergone CN. Among patients who got CN, 85.3% were treated with upfront surgery while 13.8% received prior systemic therapy ( P = 0.001). The study population was predominantly Caucasian (89.2%) and male (70.6%). Patients who underwent CN were younger (median age 61 vs. 65 years, P = <0.001). Large primary tumors and clinically node-negative status were associated with higher odds of CN (T4 disease - odds ratio (OR) for 1.49, 95% CI 1.13-3.44, P = 0.03; cN0 disease - OR 1.56, 95% CI 1.23-4.56, P = 0.04). OS after 1 year was significantly higher in patients who underwent CN (66.8% vs 33.2%. P <0.001). On multivariate analysis, CN was independently predictive of improved OS with a hazard ratio (HR) of 0.53 and 95% CI 0.41-0.68, P <0.001. Conclusions: In this large retrospective analysis, CN was associated with improved OS among patients with mRCC receiving ICI-based therapies. Our findings suggest that despite recent advances in systemic therapies for mRCC, CN retains an important role in carefully selected patients.[Table: see text]
Tumor genomic landscape in younger compared to older patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC).
Authors: Tripathi Nishita , Li Haoran , Jo Yeonjung , Sayegh Nicolas , Tandar Clara , Nussenzveig Roberto , Haaland Benjamin , Cheney Jackson , Goel Divyam , Nordblad Blake , Gupta Sumati , Maughan Benjamin L. , Agarwal Neeraj , Swami Umang 
Published: February 2022

373 Background: Renal cell carcinoma is predominant in 6th to 8th decade of life. Younger pts are more likely to have symptomatic tumors on presentation but with favorable pathological features and disease specific survival (PMID: 17092632). Herein, we hypothesized that the genomic landscape for pts with onset of renal cell cancer at a younger age is distinct from those with late age of onset. Methods: In this IRB-approved retrospective study, pts with mccRCC and tumor comprehensive genomic profiling (CGP) available from a CLIA-certified laboratory were evaluated. Among these, the pts in the first and fourth quartiles of age were included in this study. Variants of unknown significance and gene with alterations (GA) present in less than 5% of pts were excluded from the analysis. A chi-square test was used to compare gene aberration frequency and p-values were adjusted for false discovery rate (FDR) using Benjamini-Hochberg (BH) correction. The median number of genomic aberrations per pt was compared using Wilcoxon rank-sum test. Results: 78 pts were eligible and included: first quartile (Range: 25-53 years; n=54) and fourth quartile (Range: 68-77 years; n=38); male vs female: 30/13 vs 20/15. The genomic aberrations observed in both groups is listed in the table. GA in VHL and PBRM1 were the most commonly observed in both groups . Most commonly observed genomic alterations in first quartile was TP53, BAP1, CDKN2B and TSC1; and fourth quartile of age was SETD2, TSC1, KDM5C and TP53. Tumor mutation burden and the frequency of gene aberrations was similar across both the cohorts. Conclusions: In these hypothesis generating data, there was no significant difference in prevalence of targetable genomic aberrations, tumor mutational burden and frequency of genomic alterations in younger vs older pts with mccRCC. The numerically higher GA in KDM5C and SETD2 (both of which contribute to epigenetic dysregulation) in older pts warrant interrogation in a larger data set. Future directions may include the investigation of epigenomic changes and transcriptomic profiling. Detailed genomic landscape of these pts will be presented in the meeting.[Table: see text]
Stage I testicular cancer: Five-year follow-up rates and reasons for non-adherence.
Authors: Karmas Tim , Holland Patrick , Matheson Kara , Wood Lori 
Published: February 2022

412 Background: For stage I testicular cancer patients, active surveillance or follow up (f/u) post treatment is an integral part of quality care. Most guidelines recommend a minimum of 5 years of f/u however, it is known that a significant proportion of patients do not meet this milestone. The goal of this project was to determine what proportion of patients did not undergo ≥ 5 years of f/u in Nova Scotia (NS) and to document the reasons why. This would allow one to develop strategies to improve compliance and quality care. Methods: A review of all patients from NS diagnosed with testicular cancer between 2006-2015 was conducted. REB approval was obtained. Data from the provincial registry and electronic medical records was used to determine date of diagnosis, relapse/death, and f/u dates. Complete f/u was defined as: a patient having tumor markers, imaging studies, and/or clinical documentation ≥ 5 after initial diagnosis or relapse. The adequacy of f/u investigations was not recorded. If follow up was < 5 years, the reason for this was recorded. Results: In this cohort, 151 patients had stage I testicular cancer; 108 with seminoma (75% on surveillance) and 43 with nonseminoma (93% on surveillance). The median age was: 35.8 years. 48 pts (31.8%) were not seen at a cancer center (until relapse in 5 pts). Excluding 2 pts who died of unrelated causes, 44 patients (29.5%) had < 5 years f/u in NS. The most common reasons were: moved or probably moved in 17 (38.6%) and patient compliance/missing ≥2 appointments in 10 (22.7%). Modifiable reasons for incomplete f/u include: discharged too early from the cancer center in 3 patients, f/u never arranged post orchiectomy in 2 patients, and care transferred to primary care which did not occur in 1 patient. 22 patients relapsed: 3 in patients with lack of ≥ 5 years of f/u causing excess morbidity in 1 case. No patients died of testicular cancer. Conclusions: The majority of men with stage I testicular cancer had ≥ 5 years of f/u in NS as recommended by guidelines. However, 30% did not, with the most common reason being that the patient moved in 39% (where they may or may not have had f/u) and noncompliance in 23%. This study reinforces the need to have a seamless transition of care for this young, mobile patient population and easy, automated, regular appointment reminders. These results have led us to explore the creation of a phone-based app to improve follow up care and transition of care.
GAMMA: Results from a phase II study for relapsed germ cell tumors using an oxaliplatin-based treatment regimen.
Authors: Ng Kenrick , Prendergast Aaron , Carter Abigail , Yogeswaran Yathushan , Alexander Susanna B. , Rudman Sarah , Wong Han Hsi , Alifrangis Constantine , Nowosinska Ewa , Berney Daniel , Shamash Jonathan 
Published: February 2022

417 Background: Following relapse from first line chemotherapy, 30-60% of patients with germ cell tumors (GCTs) can be salvaged with further chemotherapy. Oxaliplatin-based therapies may offer reduced toxicity. Methods: Eligible patients with GCTs who progressed following cisplatin-based chemotherapy were recruited into this single-arm, phase II clinical trial (NCT01782339). Participants were recruited from six centers and received four 21-day cycles of: Actinomycin D 1mg/m2, high dose Methotrexate 5-8g/m2 day 1, Paclitaxel 80mg/m2 days 1, 8 and 15, Oxaliplatin 85mg/m2 days 4 and 8 with Pegfilgrastim support. Participants underwent an FDG-PET scan at baseline, prior to cycle 2 and on completion of treatment. The primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Results: 44 patients received at least one dose of the study medication between November 2012 and February 2020. In this full analysis set (FAS) population, the median age was 38 (range 20-57), with 9 (20%) with seminoma, 23 (52%) non-seminoma and 12 (27%) of other histology. 31 (70%) patients had at least intermediate risk disease by IPFSG risk group criteria (n = 16, 36% intermediate risk, n = 6, 14% high risk, n = 9, 20% very high risk). 39 patients received 2 or more cycles of the treatment regimen and were deemed part of the subgroup of patients in the evaluable population. The ORR of the FAS population was 52.3% and 59.0% in the evaluable population. The metabolic response rate (MRR) was 52.3% in the FAS population and 59.0% in the evaluable population. The median radiological PFS in the FAS population was 17.0 months (95% CI, 5.7 months- not reached, NR) with a radiological PFS rate at two years of 38.7% (95% CI, 22.3%-54.9%). The median combined radiological or tumour marker PFS in the FAS population was 8.3 months (95% CI, 2.6 months-17.4 months) with a combined radiological or tumour marker PFS rate at two years of 28.9% (95% CI, 16.0%-43.1%). At a median follow-up of 26.8 months, the median OS in the FAS population was not reached (95% confidence interval [CI], 17.0 months-NR) with an OS rate at two years of 62.5% (95% CI, 46.1%-75.2%). Toxicity data and correlation between early metabolic response and outcomes will be presented at the meeting. Conclusions: The GAMMA chemotherapy regimen has demonstrated encouraging anti-tumor activity in relapsed GCT, despite recruiting a cohort of patients with relatively unfavorable outcomes. Clinical trial information: NCT01782339.
Molecular analysis of primary testicular germ cell tumor and matched metastatic teratomas.
Authors: Savelyeva Anna , Wang Feng , Guo Lei , Lafin John T. , Jia Liwei , Medvedev Kirill , Lewis Cheryl , Kapur Payal , Margulis Vitaly , Woldu Solomon L. , Meng Xiaosong , Grishin Nick , Amatruda James F. , Xu Lin , Bagrodia Aditya 
Published: February 2022

425 Background: Metastastic teratoma (MT) is a unique germ cell tumor (GCT) subhistology characterized by resistance to platinum-based chemotherapy. Metastatic teratoma requires complete surgical excision, usually via retroperitoneal lymph node dissection (RPLND), following chemotherapy as a part of multidisciplinary GCT care. Molecular characterization of post-chemotherapy metastatic teratoma along with companion pre-chemotherapy testicular primary tumors could inform 1) the origin and differentiation site of metastatic teratomas, 2) mechanisms of platinum-resistance, 3) novel therapeutic options for patients with unresectable teratomas. Methods: We performed integrated molecular analysis for 16 primary germ cell tumors and 18 metastatic teratomas, 11 were matched tumor/metastasis pairs. All teratomas in our cohort were collected after induction platinum-based chemotherapy. In addition to SNV analysis, we conducted a chromosomal copy number gain and loss analysis for selected teratomas, matched primary tumors and primary teratomas from the TCGA. Results: Metastatic teratomas as well as their tumors of origin had low tumor mutation burden (0.65 and 0.47 accordingly). Amongst 583 SNVs detected in the study cohort, only two (KRAS p.Gly12Asp and KRAS p.Gly12Val) were previously described as oncogenic. Analysis of SNVs in proteins playing key roles in oncogenic signaling [1] showed that TP53 and Ras pathways were the most affected in metastatic teratomas. The majority of metastatic teratomas possess gain of 3p11.1 and loss of 10q26.3, 16p11.2, 19p13.2, 19q12 and 22q12.3 loci. Within 3p11.1 we did not identify any previously described oncodrivers. However, 5 chromosomal loci with lost heterozygosity contained 16 previously annotated tumor suppressor genes (15 protein coding and 1 microRNA, MIR199A1). Amongst those, GADD45GIP1 inhibition (growth arrest and DNA-damage-inducible, gamma interacting protein 1) is known for playing a role in cisplatin resistance through mechanism of cellular senescence [2]. Conclusions: Metastatic teratoma in our cohort is characterized by low tumor mutational burden, recurring copy number changes, and lack of recurring SNVs. Molecular insight of teratoma may inform disease biology and treatment. References: Sanchez-Vega, Francisco et al. “Oncogenic Signaling Pathways in The Cancer Genome Atlas.” Cell vol. 173,2 (2018): 321-337.e10. Nakayama, Kentaro et al. “Nucleus accumbens-1/GADD45GIP1 axis mediates cisplatin resistance through cellular senescence in ovarian cancer.” Oncology letters vol. 13,6 (2017): 4713-4719.
Inherited germline variants in urothelial cancer: A multicenter whole-exome sequencing analysis.
Authors: Kohlmann Wendy , Nix David , Atkinson Aaron , Boucher Kenneth M , Kolesar Jill , Singer Eric A. , Edge Stephen B. , Quintana Branda , Churchman Michelle L. , Feng Bingjian , Graham Laura , Carpten John D. , Sanchez Alejandro , Zakharia Yousef , Byrne Lindsey , Jain Rohit K. , Nepple Kenneth G. , Shabsigh Ahmad , Chahoud Jad , Gupta Sumati 
Published: February 2022

451 Background: Outside of Lynch syndrome, few genetic factors have been associated with urothelial cancer (UC). This project seeks to describe the frequency of germline variants in a multi-center UC cohort. Methods: Patients diagnosed with UC from 1980 to 2019 and consented to the Total Cancer Care protocol by members of the Oncology Research Information Exchange Network (ORIEN) were included in the study. The ORIEN program includes a convenience sample of cases with both germline and tumor samples available, though this analysis was germline only. Whole exome sequencing data were analyzed using a GATK best practices for germline variant analysis. A series of quality control (allele frequency > = 0.3, read depth > = 20, genotype quality > = 20), annotation, functional impact (loss of function/splicing), and region (cancer predisposition genes/pathways) filters were applied to identify variants of significant consequence. Results: 348 exomes were evaluated. This identified 60 variants classified as pathogenic/likely pathogenic (P/LP) and 17 novel, high impact variants in genes associated with high, moderate, or recessively inherited cancer risk in 77 individuals (22.1%). 15 (4.5%) had P/LP variants in genes associated with a high or moderate cancer risk, and 10 (3%) of these variants were considered to be clinically actionable with associated with cancer screening, risk reduction or treatment recommendations. The high/moderate risk genes with P/LP variants included CHEK2 (n = 5), FANCM (n = 4), MSH6 (n = 2) and single cases of MSH2, BRCA2, ERCC3, and BRIP1. The average age of diagnosis in those with and without a high/moderate risk P/LP variant was 67.6 (57-80 yrs) and 68.9 (45-91 yrs). Family history of cancer was reported for 73% of those with a germline LP/PV and 60% of those without, but this trend was not significant (p =.44). Conclusions: Individuals with UC have a high frequency of germline variants that warrant further study for association with cancer risk. A smaller, but significant portion also carry germline variants that may be clinically relevant to them and/or family members. Currently UC is not included in genetic testing criteria. This study adds to the growing body of research indicating that diverse types of cancer patients harbor germline variants. Strategies for expanding testing should be considered.
Impact of care fragmentation in patients receiving neoadjuvant chemotherapy and radical cystectomy for bladder cancer.
Authors: Riveros Carlos , Chalfant Victor , Balaji KC 
Published: February 2022

468 Background: Neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is the standard of care for muscle-invasive bladder cancer (MIBC). However, the impact of care fragmentation on the outcomes of patients receiving NAC and RC for MIBC is not well defined. Methods: The National Cancer Database was queried for adult (≥18 years old) patients with cT2-T4aN0M0 urothelial carcinoma of the bladder receiving NAC followed by RC between 2004 and 2017. Patients were dichotomized based on whether they received fragmented care (FC, defined as receiving NAC at a different facility from RC) or integrated care (IC, defined as receiving NAC and RC at a single facility). Descriptive statistics were used to characterize the two groups based on demographic and therapeutic profiles. Overall survival was compared between patients who received FC versus IC. Statistical analyses include Chi-squared tests, t-tests, Kaplan-Meier with log-rank test, and Cox regression analysis. Results: A total of 5054 patients received NAC followed by RC: 1848 (36.6%) received FC and 3206 (63.4%) received IC. Greater travel distance, private insurance, and treatment at a community cancer program were associated with FC whereas age, sex, race, median income, education level, rurality, and comorbidity burden were not. While patients who received FC had a longer time to initiation of NAC (40 vs. 37 days, p< 0.001), there was no significant difference in median overall survival (OS) (84.3 vs. 92.8 months, p= 0.37). On multivariable Cox regression analysis, age, comorbidity burden, stage, lymphovascular invasion, and surgical margins were associated with OS, while FC was not (hazard ratio: 1.03; 95% confidence interval 0.94-1.13; p= 0.51). Conclusions: Although care fragmentation was associated with a slight delay in the initiation of NAC, long-term survival rates were similar between the FC and IC groups.[Table: see text]
Sequential intravesical valrubicin and docetaxel for the treatment of nonmuscle invasive bladder cancer.
Authors: McElree Ian Mitchell , Packiam Vignesh T. , Steinberg Ryan L. , Mott Sarah L. , Gellhaus Paul T. , Nepple Kenneth G. , O'Donnell Michael A. 
Published: February 2022

496 Background: Intravesical gemcitabine-docetaxel (Gem/Doce) has emerged as an efficacious and well-tolerated therapy for NMIBC. At first cytoscopic evaluation, success rate for BCG failures is 75-80% with 60% of responders remaining disease free at 24 months. Success rates are even higher for BCG naïve patients with close to 90% disease free at 3 months, and 93% of responders HG disease free at 24 months. There is an unmet need for effective bladder-sparing regimens for Gem/Doce failures. FDA-approved agents in this setting have poor long-term efficacy; Valrubicin has an 8% 24-month disease free rate, and recently approved Pembrolizumab has less than 20% complete response at 1 year. Based on poor efficacy of alternatives, we evaluated sequential intravesical valrubicin-docetaxel (Val/Doce) as a rescue therapy for NMIBC. Methods: We retrospectively identified all patients with NMIBC who were treated with Val/Doce between April 2013 and June 2021. Patients were included with intent to receive 6 weekly intravesical instillations of sequential 800 mg valrubicin and 37.5 mg docetaxel after complete TURBT. Monthly maintenance of 2 years was initiated if disease free at 3-month cytoscopic evaluation. The primary outcome was recurrence-free survival (RFS). Progression events included the development of muscle invasive or metastatic disease as well as any cystectomy. Survival was assessed using the Kaplan-Meier method and log rank test, indexed from start of Val/Doce induction. Surveillance was performed according to AUA guidelines. Results: The final cohort included 75 patients with median follow-up of 21 months. Of these patients, 12 were treated with Val/Doce for low-grade Ta disease, with 60% disease free at 2 years and no subsequent HG occurrences. The remaining 63 patients had high-grade disease of which 86% were BCG failures and 89% were Gem/Doce unresponsive. The 2 year RFS for high-grade patients was 39%. CIS was present in 56% of the cohort. RFS was similar for those with and without CIS. Progression occurred in 12 of the patients with high-grade disease. Of note, 10 underwent cystectomy and 2 died of metastatic bladder cancer, yielding a bladder cancer specific death rate of 3%. Overall and cystectomy-free survival was 88 and 85% at 24 months, respectively. The most commonly reported side effects were bladder spasms (24%), urinary frequency (13%), and dysuria (11%). There were 3 patients who could not tolerant a full induction course. Conclusions: Sequential intravesical valrubicin-docetaxel will rescue a substantial portion of patients with HG NMIBC failing Gem/Doce or BCG. Thus, the regimen allows a high proportion of patients ( > 80%) to retain their bladders with an acceptable ( < 20%) progression rate without succumbing to bladder cancer-related death ( < 5%).[Table: see text]
Real-world study of chemotherapy plus immunotherapy versus chemotherapy alone as neoadjuvant treatment guided bladder-sparing therapy for localized muscle-invasive bladder cancer.
Authors: Shen Yali , Wen Feng , Zhang Peng , Lin Tianhai 
Published: February 2022

499 Background: Bladder-preserving combined-modality therapy has been a popular research field as an alternative to radical cystectomy for selected patients with localized muscle-invasive bladder cancer (MIBC). This real-world study aimed to compare the efficacy of neoadjuvant chemotherapy plus immunotherapy versus chemotherapy alone as one of bladder-sparing therapies for localized MIBC. Methods: Patients with cT2-4bN0-3M0-1a pathological and imaging diagnosed MIBC were included in the study. Either chemotherapy (gemcitabine and cisplatin/carboplatin) plus immunotherapy (PD-1 checkpoint inhibitor, including pembrolizumab，tislelizumab and toripalimab) or chemotherapy alone were given as patients’ wish. The primary endpoint was complete response rate (CR, T0/Ta/Tis), and the secondary endpoints were disease control rate (DCR), progression-free survival (PFS), bladder-intact disease-free survival (BI-DFS) and toxicity. Results: In total, 41 patients were included, 25 in combination group and 16 in chemotherapy group respectively. The baseline characteristics were well balanced in two groups. Median follow-up time was 15.3 ±4.4 months(m). No patient died. The efficacy evaluable population was consisted of 34 pts (22 in combination group; 12 in chemotherapy alone group). The CR rate for combination group was 50.0% and 0 for chemotherapy alone group. One patient suffered from disease progression in combination group and three in chemotherapy group. The DCRs for combination group and chemotherapy group were 95.5% and 66.7%, respectively ( p= 0.003). Twelve patients had radiotherapy and six patients had radical cystectomy followed by neoadjuvant treatments in combination group. And two patients had radiotherapy and three patients had radical cystectomy in chemotherapy group. The one-year PFS rates were 95.5% and 62.5% for combination group and chemotherapy group( p= 0.010), and the one-year BI-DFS were 66.1% versus 27.5% respectively( p= 0.159). The bladder-preserving combined-modality therapies used were well-tolerated with acceptable and manageable toxicities. Grade ¾ hematological system adverse events were 15.9% and 6.4% in combination group and chemotherapy group, respectively ( p= 0.021). Conclusions: Neoadjuvant chemotherapy plus immunotherapy showed better efficacy compared with chemotherapy alone as an important bladder-sparing therapy for locally advanced MIBC with acceptable and manageable toxicities.