bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rates of retroperitoneal lymph node dissection for stage I non-seminomatous germ cell tumors: Results from the National Cancer Database.
Authors: Haseebuddin Mohammed , Handorf Elizabeth , Kutikov Alexander , Waingankar Nikhil , Plimack Elizabeth R. , Uzzo Robert G. , Smaldone Marc C. 
Published: February 2017

395 Background: Per existing best practice guidelines, careful observation with serial imaging (active surveillance) or primary chemotherapy have supplanted primary retroperitoneal lymph node dissection (RPLND) for stage I non-seminomatous germ cell tumors (NSGCT). Hypothesizing that rates of primary RPLND have declined over the past decade, our objective was to assess temporal trends in primary treatment for stage I NSGCT using a large national cancer registry. Methods: The National Cancer Database (NCDB) was queried for all patients diagnosed with stage I NSGCT from 1998-2011. Temporal trends for receipt of primary RPLND, chemotherapy, or observation (defined as no treatment) were assessed. Adjusting for patient, demographics (age, ethnicity, race, insurance status, education, income, geographic location), and clinicopathologic characteristics (stage), multivariable logistic models were used to examine the association between available covariates and receipt of primary RPLND. Results: Of 15,822 patients identified over the study period, 9,001 (56.9%), 2,937 (18.6%), and 3,884 (24.5%) underwent observation, RPLND, and chemotherapy respectively. While rates of observation minimally changed over time (56.3 to 55.0%, p=0.85), a significant decrease in utilization of RPLND (23.0 to 12.4%, p<0.001) was matched by a significant increase in receipt of primary chemotherapy (20.7 to 32.5%, p<0.001). Rates of RPLND declined across all age groups—age < 30 (24.3% to 12.1%, P<0.0001), age 30-39 (21.6% to 13.8%, p <0.0001), age 40-49 (23.1% to 11.4%, p<0.0001), age>50 (20.0% to 11.7%, p = 0.02). Following adjustment, stage T2 (OR 0.79 [CI 0.72-0.87]) and T3 (OR 0.33 [CI 0.24-0.96]), and age categories 40-49 years (OR 0.83 [CI 0.72-0.94]) and ≥50 years (OR 0.66 [CI 0.52-0.82]) were associated with decreased utilization of RPLND. Conclusions: In hospitals reporting to the NCDB, utilization of primary RPLND for stage I NSGCT has significantly decreased over the last decade, while receipt of primary chemotherapy has increased over the same period. While employed in more than 50% of patients, rates of observation remain unchanged.
Risk-stratified treatment of patients with metastatic germ cell tumor with progression after first-line therapy.
Authors: Gunnarsson Orvar , Hwang Wei-Ting , Squillante Christian Michael , Nathanson Katherine L. , Stadtmauer Edward A. , Vaughn David J. 
Published: February 2017

398 Background: The optimal management of patients with metastatic germ cell tumor (GCT) who experience progression after first-line (FL) therapy is controversial. A risk-stratified approach was introduced in 2005. Favorable risk patients received 4 cycles of paclitaxel, ifosfamide, cisplatin (TIP); unfavorable risk patients received 2 cycles of TIP followed by 2 cycles of high-dose chemotherapy [(HDCT); carboplatin and etoposide with autologous stem cell support]. Favorable risk was generally defined as gonadal primary and relapse > 6 months after CR or marker negative PR to FL therapy; all others were unfavorable risk. The aim of this study is to present survival outcome of this risk-stratified approach at a single institution. Methods: A chart-based retrospective review was conducted on all patients with metastatic GCT who experienced progression after FL therapy from 2005 to 2013. Data were collected on baseline demographics and disease characteristics. Progression-free survival (PFS) and overall survival (OS) were calculated for favorable and unfavorable risk patients. Results: 37 patients were identified and included for analysis. Patients characteristics: Caucasian 92%; median age 27 years; gonadal primary 84%; non-seminoma, 81%. 16 (43%) favorable risk patients received TIP x 4; 21 (57%) unfavorable risk patients received TIP x 2 followed by HDCT x 2. The median time for follow-up was 16 months. Favorable risk patients: 2- and 4-year PFS of 60% and 45%; 2- and 4-year OS of 74%. Unfavorable risk patients: 2- and 4-year PFS of 41% and 27%; 2- and 4-year OS of 55% and 34%. Both IGCCCG risk classification at initial diagnosis and IPFSG risk classification at relapse had prognostic validity for OS (log rank p ≤ 0.05) but not PFS (log rank p = 0.065–0.080). Conclusions: Risk-stratified treatment of patients with metastatic GCT with progression after FL therapy may result in the best risk/benefit ratio. However, the optimal management of these patients is still not known and prospective randomized comparisons are needed.
Retrospective analysis of chemotherapy for the patients with advanced bladder adenocarcinoma.
Authors: Oh Sung Yong , Kim Young Sam , Lee Ji Hyun , Kim Moonjin , Choi Young Jin , Soel Yong Mi , Park Min Jae , Kim Ki Hyang , Park Lee Chun , Kang Jung Hun , Hwang In-Gyu , Kim Hyo Song , Lim Seung Taek , Rha Sun Young , Lee Soonil 
Published: February 2017

399 Background: By definition, primary adenocarcinoma of the bladder (PAB) is a malignant neoplasm derived from urothelium of the bladder showing histologically pure glandular differentiation. Because of its rarity, role of chemotherapy for metastatic adenocarcinoma of bladder is still questionable. Therefore, we performed a retrospective analysis of the clinical features and chemotherapy outcomes of metastatic PAB to evaluate the clinical findings at presentation, overall survival (OS) and progression-free survival (PFS) and prognostic factors. Methods: Eligible patients for this retrospective analysis were initially diagnosed with adenocarcinoma and presented with a clinically no other primary site of origin. The collected data included age, gender, performance status, stage, hemoglobin, albumin, initial date of diagnosis, treatment modality utilized, response to treatment, presence of relapse, last status of patient, and last date of follow-up. Results: We retrospectively reviewed 29 patients who treated with chemotherapy as metastatic PAB at 10 Korean medical institutions from 2004 to 2014.The median age of patients was 58 years (range, 17 to 78 years) and 51.7% of the patients were female. Fifteen patients were urachal adenocarcinoma. Of 27 symptomatic patients, 22 experienced gross hematuria. Ten patients had two or more metastatic sites of the lungs (51.7%), peritoneum (41.4%), and ovary (20.7%), as the most common sites. Twelve patients were treated with 5-FU based chemotherapy, 5 were gemcitabine based, 3 were taxane and adriamycin based, and others. 13 of them achieved CR (10.3%) or PR (34.5%). Median PFS and OS for all patients were 10.6 months (95% confidence interval [CI], 9.5 to 11.6 months) and 24.5 months (95% CI, 1.2 to 47.8 months), respectively. In the prognostic factor analysis, the cases of urachal adenocarcinoma had worse tendency in PFS and OS (p=0.024 and P=0.046, respectively). Conclusions: Metastatic Despite most of chemotherapy, PFS and OS were short especially in urachal carcinoma, however, there were some long-term survivors, therefore, additional research on the predictive markers of several clinical, pathological differences and their treatments will be needed.
Prognostic factor for overall survival in the "difficult-to-treat" germ cell tumor patients.
Authors: Nakamura Terukazu , Oishi Masakatsu , Ueda Takashi , Shiraishi Takumi , Nakanishi Hiroyuki , Naya Yoshio , Hongo Fumiya , Okihara Koji , Miki Tsuneharu 
Published: February 2017

402 Background: Our previous observation showed germ cell tumor (GCT) patients who finished at first-, second- or third-line chemotherapy obtained good overall survival. On the other hand, patients with 4th line-or-after chemotherapy showed much poorer outcome. The aim of this study was to investigate the prognostic factor for overall survival in the patients with 4th-line-or-after chemotherapy. Methods: Between August 1998 and December 2013, seventy-four GCT patients had 4th line-or-after chemotherapy at our institution. These patients were defined as ‘difficult-to-treat’ GCT patients in this study. We retrospectively assessed clinical and therapeutic parameters. Median age was 33 y.o.(range;19-55). Nonseminoma was found in 86.5%. Good, intermediate and poor prognosis by IGCCC was 23, 17 and 26 cases, respectively. With regard to IGCCC at salvage, very low, low, intermediate, high and very high was 2, 7, 10, 18 and 6 cases, respectively. Results: Fiver-year overall survival was 55.6%. Choice of 2nd line or 3rd line chemotherapy did not influence overall survival, for example, VeIP (vinblastine, ifosfamide, cisplatin) or VIP (etoposide, ifosfamide, cisplatin) versus other chemotherapy as 2nd line therapy (5-y OS; 55.2% and 56.3%, log-rank, p=0.78). The identical result was observed in paclitaxel-containing therapy such as TIP versus other chemotherapy (paclitaxel, ifosfamide, cisplatin) (5-y OS; 52.8% and 57.1%, log-rank, p=0.90). In the choice of 4th line chemotherapy, gemcitabine-containing regimen was not superior to other chemotherapy (5-y OS; 57.0% and 55.3%, log-rank, p=0.98). Statistical significant parameters were primary site, IGCCC at salvage, required chemotherapy line and serum tumor marker (STM) normalization by univariate analysis. Multivariate analysis showed independent prognostic factor for overall survival was normalization of serum tumor marker during chemotherapy (Hazard Ratio;0.12, 95% Confidence Interval;0.02-0.62, p=0.01). Conclusions: STM normalization is thought to be mandatory for overall survival in the management of ‘difficult-to-treat’ advanced GCT patients.
Renal nephrometry score and predictors of pathologic upstaging in patients undergoing partial and radical nephrectomies.
Authors: Pruthi Deepak Kumar , Chhibba Ruchi , Drachenberg Darrel E , McGregor Thomas 
Published: February 2017

412 Background: To examine the predictive capability of pre-operative anatomic imagining characterization of the R.E.N.A.L. Nephrometry Score (RNS) in assessing pathologic upstaging of clinical T1 (cT1) lesions to pathologic T3 (pT3) in partial and radical nephrectomy specimens. Methods: We conducted a retrospective review of all patients undergoing radical and partial nephrectomies between January 1, 2011 and May 31, 2014 for cT1 renal masses. All pre-operative imaging scans were reviewed and the R.E.N.AL. Nephrometry score (radius for tumor size as maximal diameter, exophytic/endophytic tumor properties, nearness of deepest portion of tumor to collecting system or sinus, anterior/posterior descriptor and location relative to polar line) was applied to each scan. Chi-square, Fisher exact test, and Student t test were utilized to examine associations. Results: Of the 229 patients who underwent partial or radical nephrectomy for cT1, 124 (54%) underwent partial nephrectomy. On pathologic evaluation 195 (85%) patients had malignancy. Of all tumors 26 (13%) were pathologically upstaged to pT3 with the majority attributable to renal sinus/fat (35%) or perinephric fat (31%) involvement. High RNS (>10) was significant in predicting pathologic T3 upstaging (p=0.039) but did not predict high grade (Furhman grade 3-4) disease (p=0.803). While a high nephrometry score trended toward predicting malignancy vs benign disease (p=0.086), a higher mean nephrometry score (7.81 vs. 6.84) significantly predicted malignancy (p=0.015). When controlled for cT1a lesions, tumor location relative to polar lines (L=3 vs. L1+2) was predictive of pT3 upstaging (24 vs. 6%, p=0.03). Age >65 was significantly associated with upstaging (26 vs. 7%, p=0.0001). Conclusions: Surveillance of small renal masses is common but high RNS and age >65 significantly predicted pathologic upstaging. Mean nephrometry score was also useful in predicting malignancy. Nephrometry score may aid in deciding on early surgical intervention.
Overall survival (OS) in Swedish RCC patients treated 2000–2012: Update of the RENCOMP study.
Authors: Lindskog Magnus , Wahlgren Thomas , Sandin Rickard , Kowalski Jan , Jakobsson Maria , Lundstam Sven , Ljungberg Börje , Harmenberg Ulrika 
Published: February 2017

413 Background: The RENal COMParison (RENCOMP) study showed a significant improvement in OS for Swedish patients diagnosed with renal cell carcinoma (RCC) and metastatic (m)RCC in the first years following the introduction of targeted agents (TAs) in 2006 (Br J Cancer 2013;108:1541). Here we investigated whether a further improvement in OS can be detected in the more recent years of the TA era. Methods: Using data from the Swedish Cancer Register (diagnosis and death records), National Patient Register (in-/out-patient visit records), and Swedish Prescribed Drug Register (prescribed/dispensed drug records), we assessed OS in RCC and mRCC patients diagnosed during two periods after (2009–2012 and 2006–2008) and one period before (2000–2005 [RCC]; 2002–2005 [mRCC]) the introduction of TAs, and factors influencing OS in mRCC. Multivariate analysis was performed using a Cox proportional hazards model, including estimates of adjusted HR. The regression model included the covariates age, gender, geographical region, institution size, nephrectomy status, diagnosis period, and TA prescription. Results: In total, 3,980, 2,956, and 5,225 RCC patients were identified from 2009–2012, 2006–2008, and 2000–2005, respectively. From 2002–2012, 4,217 patients met the criteria for mRCC diagnosis. RCC patients diagnosed 2009–2012 and 2006–2008 had a significant improvement in OS compared with patients diagnosed 2000–2005 (median OS: not reached and 86 vs. 48 months, respectively; both P<0.001 [log-rank]). Likewise, mRCC patients diagnosed 2009–2012 and 2006–2008 had a significant improvement in OS compared with patients diagnosed 2002–2005 (median OS: 18.0 and 13.0 vs. 10.0 months, respectively; both P<0.001 [log rank]; with adjusted HR [95% CI] of 0.76 [0.69–0.83] and 0.97 [0.89–1.06], respectively). Factors significantly associated with longer OS in mRCC were (HR, 95% CI): female gender (0.88, 0.82–0.94), lower age (0.97, 0.97–0.98), prior nephrectomy (0.57, 0.53–0.61), and a TA prescription (0.84, 0.77–0.91). Conclusions: A continued significant improvement in OS for RCC and mRCC patients was shown, reflecting intensified medical and surgical treatment, more available TAs, and increased clinical experience.
The association between obesity and incidence of total and fatal renal cell carcinoma in two prospective cohorts.
Authors: Wilson Kathryn M , Cheng Jed-Sian , Sanchez Alejandro , Graff Rebecca , Rodriguez Dayron , Feldman Adam S. , Barrisford Glenn , Bechis Seth , Blute Michael , Stampfer Meir J. , Chang Steven L. , Giovannucci Edward L. , Albiges Laurence K. , Choueiri Toni K. , Cho Eunyoung , Preston Mark A 
Published: February 2017

414 Background: Recent studies suggest an “obesity paradox” in renal cell carcinoma (RCC), in which obese people are more likely to be diagnosed with RCC, but are less likely to die of the disease. We studied the association of body mass index (BMI) with risk of both total and fatal RCC in two large prospective cohorts. Methods: The Nurses’ Health Study (NHS) consists of 117,097 women followed since 1976, and the Health Professionals Follow-up Study (HPFS) consists of 48,268 men followed since 1986. Height and weight were reported at baseline and updated biennially through 2008, with disease follow-up through 2010. We used multivariable Cox proportional hazards models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the incidence of both total and fatal pathology-confirmed RCC by BMI immediately prior to diagnosis. Models were adjusted for diabetes, hypertension, smoking, alcohol intake, NSAID use, physical activity, and parity in women. Results: We confirmed 349 cases of RCC, including 103 fatal cases, in NHS, and 226 cases in HPFS, with 46 fatal cases. Compared to women with normal BMI (18.5-24.9 kg/m2) immediately prior to diagnosis, obese women (BMI≥30) had an increased risk of RCC (HR 1.38, 95% CI: 1.03-1.84, p-trend=0.004), adjusting for possible confounders. The HR for fatal RCC was similar but not statistically significant (HR 1.35, 95% CI: 0.79-2.29, p-trend=0.22). Obese men had a non-significantly increased risk of RCC (HR 1.45, 95% CI: 0.96-2.21, p-trend=0.05), with a significantly increased risk of fatal RCC (HR 2.56, 95% CI: 1.11-5.90, p-trend=0.13). Among women, the associations with baseline BMI (1976) were somewhat stronger (HR 1.88, 95% CI: 1.36-2.61, p-trend<0.0001 for total; HR 1.98, 95% CI: 1.07-3.66, p-trend=0.002 for fatal). For men the association with baseline BMI (1986) was weaker for fatal RCC (HR 1.34, 95% CI: 0.50-3.58, p-trend=0.27). Conclusions: Our results support that obesity is a risk factor for RCC incidence and also suggest that it is adversely associated with fatal RCC. These results are stronger for women than for men, though this may be due to the lower number of cases among men.
Evaluation of post-operative complications and prolonged length of stay following cytoreductive nephrectomy.
Authors: Gershman Boris , Moreira Daniel M. , Boorjian Stephen A. , Lohse Christine M. , Cheville John C. , Costello Brian Addis , Leibovich Bradley C. , Thompson Robert Houston 
Published: February 2017

420 Background: Cytoreductive nephrectomy (CN) has been associated with significant morbidity, but there is little data identifying patients at increased risk. We evaluated the association of clinicopathologic features with early post-operative complications and prolonged length of stay (pLOS) among CN patients. Methods: We identified 294 patients treated with radical nephrectomy for M1 renal cell carcinoma between 1990 and 2009 at the Mayo Clinic. All complications within 30 days of surgery were reported using standardized methodology according to the Clavien classification. Associations with the presence of any early complication and pLOS (defined as ≥8 days, the top 25th percentile) were evaluated using logistic regression models. Results: Thirty-five (12%) patients experienced at least one early complication and 15 (5%) patients experienced at least one Clavien grade ≥3 early complication. The median LOS was 6 days (IQR 5-7), and 68 (23%) patients had a pLOS. On univariate analysis, liver metastases, symptomatic presentation, intraoperative transfusion, and pathologic nodal stage were significantly associated with both early complications and pLOS (Table). Two multivariate models were constructed. In Model 1 (limited to pre-operative features), only liver metastases (p<0.01) were associated with early complications while liver metastases (p=0.01) and open approach (p=0.02) were associated with pLOS. In Model 2 (all variables included), liver metastases (p=0.01), intraoperative transfusion (p<0.01), and high nuclear grade (p<0.01) were associated with early complications while intraoperative transfusion (p<0.01) and positive nodes (p=0.05) were associated with pLOS. Conclusions: CN was associated with a low incidence of early post-operative complications, particularly Clavien ≥3 complications. Presence of liver metastases and intraoperative transfusion were independently associated with increased risk of both complications and pLOS. [Table: see text]
Whole-exome sequencing (WES) predicting two extreme phenotypes of response to VEGF-targeted therapies (VEGF-TT) in patients with metastatic clear cell renal cell carcinoma (mRCC).
Authors: Fay Andre Poisl , Van Allen Eliezer Mendel , Murray Bradley , Albiges Laurence , Signoretti Sabina , Ho Thai Huu , Hakimi A. Ari , Mickey Suzanne S , Stanton Melissa L. , Bellmunt Joaquim , McDermott David F. , Atkins Michael B. , Garraway Levi A. , Kwiatkowski David J. , Choueiri Toni K. 
Published: February 2017

422 Background: There is significant variability in the response to VEGF-TT in mRCC with no validated predictive biomarkers. We hypothesized that whole exome analysis might identify markers of response and resistance to VEGF-TT in mRCC. Methods: mRCC patients who received first-line sunitinib or pazopanib and were in two extreme phenotypes of response were identified. Extreme responders (ER) were defined as PR or CR for ≥3 years (n=10) and primary refractory patients (PRP) were defined as PD within the first 3 months of therapy (n=10). WES was performed in pre-treatment specimens and established Broad Institute analytical pipelines were utilized to identify point mutations and copy number alterations across the exome. ER (n=4) and PRP (n=4) who were part of TCGA project for clear-cell RCC were included in this analysis. Nonsense, missense and indel mutations in established or novel RCC genes were investigated. Results: IMDC prognostic scores were not significantly different between the two groups. VHL mutations were observed at similar frequency in ER and PRP, overall 57%. Mutations in PBRM1 were identified in 7 ER (50%) vs. 1 PRP (7%) (p=0.03). In addition, mutations in TP53 were only found in PRP (p=0.09). No other gene had mutations that were associated with either response or primary refractory disease (Table). Conclusions: In this pilot study, PBRM1 mutations were associated with extreme response to VEGF-TT. However, this was exploratory, and multivariable analysis was not performed. Analysis of additional patient samples is ongoing to confirm or refute this association. If true it suggests that epigenetic effects of PBRM1 mutation may contribute to response to VEGF-TT in mRCC. [Table: see text]
Evaluation of the effects of neoadjuvant pazopanib for renal cell carcinoma on intratumor genetic heterogeneity.
Authors: Ferguson Jed , McKibben Maxim , Parker Joel S , Wallen Eric , Wood Christopher G. , Powles Thomas , Rathmell Kimryn 
Published: February 2017

425 Background: The prevalence of intratumoral genetic heterogeneity in renal cell carcinoma (RCC) has recently been elucidated, and the clinical implications are currently under investigation. The effects of neoadjuvant pazopanib on intratumoral genetic heterogeneity in RCC are unknown. Methods: With IRB approval and informed consent, 5 patients with clinically localized clear cell RCC were treated with pazopanib chemotherapy for ≥8 weeks prior to radical nephrectomy. Prior to treatment, the tumors were sampled by percutaneous core biopsy for histologic and genetic analysis. Peripheral leukocytes were collected for wild-type genetic analysis. Following nephrectomy, tumors were sampled for histologic and genetic analysis. DNA was extracted from all samples and ultra-deep multiregion exome genetic sequencing was performed to identify genetic mutations. Mutant allele frequencies were calculated and compared between pre- and post-pazopanib samples. Hierarchical cluster analysis was performed to evaluate intra- and inter-tumoral heterogeneity, and the fraction of private mutations was tabulated to evaluate change in clonality after pazopanib treatment. Results: Patients age ranged from 52 to 75, and tumors ranged from T2 to T4 (all cN0M0). Percent change of tumor volume after treatment ranged from -10% to -33%. Hierarchical cluster analysis of genetic mutations revealed that all pre- and post-pazopanib sample pairs clustered more closely with each other than with the other tumors, suggesting that intertumoral heterogeneity overshadowed intratumoral heterogeneity. Important genetic mutations in RCC (such as VHL, PBRM1, and SETD2) were highly represented in our dataset, thus validating our approach. After pazopanib, total numbers of mutations as well as the fraction of private mutations decreased in all tumors, showing an increased clonality with pazopanib therapy. Conclusions: RCC is highly genetically heterogeneous. However, this heterogeneity decreases with neoadjuvant pazopanib. These data have implications for the accuracy of percutaneous biopsy to predict tumor biology, and begin to reveal insights into the biologic and genetic response of these tumors to pazopanib.