bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is surveillance without immediate treatment an option for newly diagnosed testicular germ-cell cancer patients with borderline size retroperitoneal lymph nodes on computed tomography scan?
Authors: Milk Nadav , Leibovitch Ilan , Keizman Daniel , Dresler Hadas , Sternberg Itay 
Published: February 2018

560 Background: The AJCC TNM Staging System for Testicular Cancer (TC) does not set a minimal diameter to define positive lymph nodes (LN) on computed tomography scan. It is common to refer to LN ≥ 1 cm in diameter as positive, even though benign LN in the borderline size of 1-1.5cm are common. Our goal is to describe the outcome of TC patients with borderline size retroperitoneal LN of undetermined significance managed initially with surveillance. Methods: We retrospectively reviewed the medical records of all TC patients treated at our institution during 2006-2016. Demographic, clinical, laboratory, imaging, pathological, treatment and surveillance data were obtained. Results: Of a total of 109 TC patients, 25 patients (22.7%) with borderline size LN were assigned to an active surveillance protocol by our tumor board. Median age at the time of orchiectomy was 37.2 years (IQR, 23.9-40.3). With a median follow-up of 3.9 years (IQR 1.7-6.5), overall survival rate in the group was 100%. Nine of 25 patients (36%) relapsed and were treated within a median of 4.9 months (IQR 2.2-5.5). Median follow-up for 16 patients who did not relapse was 3.4 years (IQR 1.5-5.4). Relapse-free survival was 71% (95% CI 48-85), and 61% (95% CI 38-77) at one and two years, respectively. Orchiectomy pathology included pure seminoma in 18/25 (72%), and a nonseminomatous tumor in 7/25 (28%). Tumor type was not associated with likelihood of relapse (p = 0.66). The median LN diameter at the time of diagnosis was 11 mm (IQR 9-12, mean 10.4). LN diameter was not associated with likelihood of relapse (p = 0.34). Patients who relapsed during follow-up were significantly younger at the time of TC diagnosis than patients who did not relapse (Median age 23.9 years [IQR 19.6-35.2] and 39.2 years [IQR 34.3-47.9] respectively, p = 0.0056). Conclusions: Surveillance alone for TC patients with borderline size LN of undetermined significance at diagnosis is a possible option and may help avoid overtreatment in 60% of these patients.
Distinguishing fibrosis/necrosis from teratoma or viable disease in the retroperitoneum in post-chemotherapy, nonseminomatous testicular germ cell tumor using quantitative CT texture analysis.
Authors: King Kevin George , Bhanvadia Sumeet , Ghodoussipour Saum , Hwang Darryl , Varghese Bino , Cen Steven Yong , Daneshmand Siamak , Duddalwar Vinay 
Published: February 2018

563 Background: In metastatic nonseminomatous testicular germ cell tumor (NSGCT), post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) is indicated for residual masses > 1 cm because of these 45% will be fibrosis/necrosis, 45% will be teratoma and 15% will be viable malignancy. There is no imaging test that reliably distinguishes lymph nodes (LNs) with tumor (teratoma or malignancy) from LNs with fibrosis/necrosis. We evaluated whether quantitative CT texture analysis (TA) could make this differentiation. Methods: Pre- and post-chemotherapy CTs (all same phase and slice thickness) were reviewed in 22 NSGCT patients with RP LNs > 1 cm post chemotherapy. After manual segmentation of RP LNs on a 3D workstation, 187 TA metrics were derived, using 2D/3D gray-level co-occurrence matrix (GLCM), 2D/3D gray-level difference matrix (GLDM), and spectral analysis. Metrics were derived 2 ways: from post-chemotherapy CTs alone, and also as a difference between pre- and post-chemotherapy CTs, resulting in 374 metrics. PC-RPLND pathology was correlated with CT data at 88 LN stations in these 22 patients. Results: 15 imaging metrics showed a significant difference (p ≤ 0.05) between LN stations with only fibrosis/necrosis and those with teratoma or viable tumor. Seven were derived from the difference between pre- and post-chemotherapy CTs: 4 using a 2D GLCM (coronal standard deviation, coronal square root of variance, coronal mean, and coronal sum of average), and 3 using a 2D GLDM (axial variance, axial square root of variance, and coronal variance). The other 8 were derived from post-chemotherapy CTs alone: 7 using a 2D GLCM (sagittal square root of variance, sagittal standard deviation, coronal square root of variance, coronal mean, coronal standard deviation, coronal sum of average, and coronal entropy) and 1 using a 2D GLDM (sagittal sum entropy). Conclusions: CT TA shows promise in differentiating necrosis from teratoma or viable tumor in RP LNs in post-chemotherapy NSGCT. A larger study is needed to further test this method, towards a long-term goal of potentially allowing some patients to avoid PC-RPLND.
Effect of number of computed tomography (CT) scans during follow-up (FUP) of patients with clinical stage I (CSI) seminoma: A trial-level meta-analysis.
Authors: Giannatempo Patrizia , Raggi Daniele , Tagliabue Elena , Catanzaro Mario , Biasoni Davide , Torelli Tullio , Stagni Silvia , Nicolai Nicola , Piva Luigi , Salvioni Roberto , Mariani Luigi , Necchi Andrea 
Published: February 2018

564 Background: Despite the overall high cure-rate for patients (pts) with CSI seminoma (sem) regardless of the intervention used, huge discrepancy exists in the number of CT scans that are proposed to pts during FUP period, mainly during active surveillance (AS). The impact of such discrepancy in diagnosing pts with a high-risk relapse was assessed in published literature with a meta-analysis (MA). Methods: We searched for arms of studies of AS or active treatment (AT, adjuvant chemotherapy and radiotherapy) in pts with CSI sem. Meta-analytic techniques were used to pool and compare study level data of AS and AT groups and to study the impact of the number of CT scans (as a continuous variable) during FUP upon the % of pts with CSIII or with IGCCCG intermediate (int) prognosis sem at relapse. Results: 22 studies were analyzed (33 arms, n = 11025 pts). 39.6% had a high-risk sem, 38.8% (n = 4274) underwent AS vs 61.2% (n = 6751) AT. The number of CT scans ≤2y ranged 4-8, and 0-7 for AS and AT groups. Overall, 922 pts experienced a relapse (651 in AS and 271 in AT arms), 73.9% <2y and 22.3% at 2-5y FUP. Statistical modeling showed that the estimated rates of CSIII relapse (6% in AS, 32% in AT group, p = 0.0068) and int prognosis relapse (2% in AS, 11% in AT group, p = 0.0051), were divergent for the two groups. A higher number of CT scans in the first 2 years of FUP tended to reduce the occurrence rate of both endpoints, but failed to reach statistical significance in AS (p = 0.334 for CSIII, unidentifiable for int prognosis relapse), as well as in AT (p = 0.438, p = 0.103). The number of CT scans in 3-5y FUP had an even weaker prognostic effect. Similar trends were observed in AS cohort after adjusting for the CSI risk group. Conclusions: In this trial-level MA we did not find a statistically-significant association between the number of CT scans performed during FUP of CSI sem pts and the diagnosis of high-risk relapses. Huge discrepancy in the total number of CT scans was generally found between arms. In contrast, as expected, the pattern of relapse of CSI sem was different according to the treatment group. Based on these results, there is room for consistently reducing the number of CT scans during FUP of CSI sem pts undergoing AS.
Outcomes of male patients with germ cell tumors and bone metastases: A mono-institutional retrospective study.
Authors: Moriceau Guillaume , Boyle Helen Jane , Bonnin Nathalie , Sajous Christophe , Peyrat Patrice , Pommier Pascal , Rivoire Michel , Flechon Aude 
Published: February 2018

570 Background: Bone metastases (BM) are considered as intermediate or poor prognosis according to the international classification of Germ Cell Tumors (GCT). The present study compares the outcomes between patients with bone disease at initial diagnosis and bone disease at relapse and between seminoma and non-seminoma GCT. Methods: We investigated retrospectively all male-patients presenting GCT with BM at initial diagnosis or at relapse, between 2005 and 2015, in a single institution. Results: Thirty-nine patients were included. Median age was 36 (from 20 to 67). Nineteen patients presented with BM at initial diagnosis (49%) and 20 patients presented BM at relapse (51%). Histologically, 13 patients (33%) presented a seminoma and 26 patients (67%) a non-seminoma GCT. Twenty-four patients (62%) had multiples bone metastatic sites. Vertebra was the most frequent location (70%). Bone surgery was performed for five patients with seminoma (38%) and four patients with non-seminoma GCT (15%). Median overall survival (OS) was 130.9 months for the 19 patients with BM at initial diagnosis and 15.2 months for the 20 patient with BM at relapse HR 5.3 95%CI[1.75;16.06], p < 0.001. Median progression free survival (PFS) was 120.10 months for patients with BM at initial diagnosis and 9.21 months for patients with BM at relapse, HR 3.02 95%CI[1.16;7.83], p < 0.0016. Survivals are longer for patients with seminoma than patients with non-seminoma GCT. Median PFS was 9.41 months for the 13 patient with non-seminoma GCT and not achieved for the 26 patients with seminoma, HR 0.15, 95%CI [0.003;0.65], p 0.001 . Median OS was 18.7 months for the 13 patient with non-seminoma GCT and not achieved for the 26 patients with seminoma, HR 0.16 95% CI [0.004;0.7], p 0.002. Conclusions: BM of GCT are associated with a worse prognosis especially for non-seminoma subtype and/or when BM arise at relapse. This data highlights the importance of the first line therapeutic strategy as the corner stone of treatment for patients with GCT.
Association of age and sex with mortality following adjuvant therapy for renal cell cancer (RCC): Subgroup analysis of the ASSURE (E2805) trial.
Authors: Mamtani Ronac , Wang Xin Victoria , DiPaola Robert S. , Dutcher Janice P. , Haas Naomi B. 
Published: February 2018

575 Background: The benefit of vascular endothelial growth factor tyrosine kinase inhibitors (VEGF-TKIs) as adjuvant therapy for RCC remains a subject of controversy. Given the uncertain risk-benefit ratio, identifying subgroups expected to derive benefit or harm from therapy could lead to a more precise approach to therapy. Because of known sex-differences in the pharmacokinetics and tissue distribution of VEGF-TKIs, we assessed the interaction of age and sex on treatment outcomes among patients in the phase III ASSURE trial (Adjuvant Sorafenib or Sunitinib for Unfavorable RCC). Methods: ASSURE included 1,943 patients with ≥ pT1b resected RCC. There was no OS or DFS benefit with adjuvant sunitinib or sorafenib relative to placebo. In this post-hoc subgroup analysis of age and sex based on the median age of 56 years, Cox regression computed hazard ratios (HR) and 95% confidence intervals (CIs) for OS and DFS with sunitinib or sorafenib compared to placebo across age- and sex-specific strata (males ≤ 56 years [n = 689], males > 56 years [n = 620], females ≤ 56 years [n = 317], and females > 56 years [n = 317]). Models were adjusted for race, histology, and UISS risk group. A 3-way interaction term was calculated for sex, age, and treatment. Results: Treatment with sunitinib was associated with increased mortality among women > 56 years (sunitinib vs placebo [HR OS 2.38; 95% CI, 1.39-4.07]), but not in women ≤ 56 years or in men of any age. Similarly, among women > 56 years, the risk of disease recurrence was increased with sunitinib relative to placebo (HR DFS 1.53; 95% CI, 1.03-2.28). There were no statistically significant differences in OS or DFS associated with sorafenib (women > 56 years: HR OS 1.50, 95% CI, 0.83-2.71; HR DFS 1.23, 95% CI, 0.81-1.89). The 3-way interaction between age, sex, and sunitinib treatment on mortality was statistically significant (p = 0.0166). Conclusions: Adjuvant sunitinib after nephrectomy was associated with increased mortality among older women, which may be explained by increased risk of RCC recurrence. These findings, if validated, highlight the importance of considering sex and age on VEGF-TKI treatment outcomes, future study designs, and RCC tumor biology. Clinical trial information: NCT00326898.
Phase II study of enzalutamide monotherapy with radiation therapy for intermediate risk prostate cancer.
Authors: Bubley Glenn , Kaplan Irving D. , Werner Lillian , Bhatt Rupal Satish , Taplin Mary Ellen , Mahoney Kathleen Margaret , Nguyen Paul ,   Taplin
Published: February 2018

58 Background: Castrating androgen deprivation therapy (ADT) is standardly prescribed in combination with radiation therapy (RT) for intermediate or high-risk prostate cancer (PCa). ADT is associated with multiple side effects including weight gain, loss of libido, hot flashes and muscle atrophy. In contrast, enzalutamide monotherapy is associated with much fewer side effects. Methods: At Dana-Farber/ Harvard Cancer Center we performed an open label phase II study of enzalutamide for 6 months as neo- and adjuvant treatment for intermediate risk PCa patients (NCCN criteria) receiving RT. The primary endpoint was the proportion of patients achieving a PSA response of ≤0.2 . This endpoint is predictive of long term PSA response in a similar risk-group of patients treated with RT and ADT. PSA values were obtained at baseline and monthly on 6 cycles of enzalutamide (160mg/day). 79.2 Gy in 44 fractions of IMRT was started between 6 and 10 weeks after the initiation of enzalutamide. Quality of life questionnaires, hormone levels and anthropomorphic measurements were obtained. Results: 45 of 60 evaluable patients had a PSA ≤0.2 at the end of 6 months of enzalutamide. With a sample size of 64 evaluable patients, if the number achieving a PSA level is ≤0.2 is 44 or more, the null hypothesis is rejected with a target error rate of alpha = 0.10. Also 54 of 60 evaluable patients had a PSA of ≤0.5ng/ml. Importantly, less than half of the participants experienced erectile dysfunction or decreased libido and these were predominantly grade I. Less than a quarter of patients reported hot flashes (all grade I). Waist circumference did not change with therapy. The most frequent grade 2 or greater events were hypertension and gynecomastia. Testosterone and free testosterone levels rose significantly on enzalutamide therapy. Conclusions: Enzalutamide monotherapy with RT may be as effective as castrating ADT, and associated with fewer side effects. Larger, randomized trials are needed to further evaluate enzalutamide monotherapy, instead of ADT, to be used in combination with RT. Clinical trial information: NCT0208988.
A randomized phase II trial of pazopanib (PAZ) versus temsirolimus (TEM) in patients (pts) with advanced clear-cell renal cell carcinoma (aCCRCC) of intermediate and poor-risk (the TemPa trial).
Authors: Tannir Nizar M. , Ross Jeremy Aaron , Devine Catherine E , Chandramohan Anuradha , Wang Xuemei , Lim Zita Dubauskas , Wang Jennifer , Corn Paul Gettys , Zurita Amado J. 
Published: February 2018

583 Background: TEM has level 1 evidence in aRCC with poor-risk disease. No trial compared a VEGFR-TKI with TEM as first-line (1L) therapy in this disease state. Methods: We randomly assigned (1:1) treatment-naïve pts with aCCRCC and > = 3 risk factors (as per Hudes et al., NEJM 2007) to receive PAZ 800 mg po qd or TEM 25 mg iv qw. Pts were offered to receive the alternative agent at disease progression (PD). The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR) and safety. A blinded radiologist assessed the radiographic response using RECIST v1.1. A sample size of 90 pts was based on an assumption of improved median PFS from 3.8 mo with TEM to 6.1 mo with PAZ. Pts were stratified by prior nephrectomy (Nx). The Kaplan-Meier method was used for PFS and OS analysis, and the Fisher’s exact test was used for comparison of ORR between PAZ and TEM. Results: The study was closed to new patient enrollment when the results of the CheckMate 214 and CABOSUN studies were presented at ESMO 2017. A total of 69 pts were eligible and evaluable (median age 61, 52 males [75%], 44 [64%] had poor-risk by IMDC criteria). Thirty pts [43%] had prior Nx. Thirty-five pts received PAZ (intermediate-risk 13, poor-risk 22) and 34 pts received TEM (intermediate-risk 12, poor-risk 22). Of the 69 pts, 67 had PD or died. The median PFS was 5.2 mo (95% CI: 3.6 –7.4) for PAZ and 2.6 mo (95% CI: 1.9 –4.2) for TEM (p = 0.16). In 1 pt, no date of death was available. Of the remaining 68 pts, 58 (85.3%) have died. The median OS was 12.0 mo (95% CI: 8.3–20.1) for PAZ and 7.4 mo (95% CI: 5.3–17.4) for TEM (p = 0.61). Sixty-eight pts were evaluable for response: 9/35 pts (26%) who received PAZ and 2/33 pts (6%) who received TEM had partial response (p = 0.046). Adverse events (AEs) were consistent with the known safety profiles of PAZ and TEM. Only 2 pts in each arm discontinued treatment due to AEs. Conclusions: PAZ extended PFS and OS and yielded a significantly higher ORR than TEM as 1L therapy in pts with aCCRCC and intermediate/poor-risk disease. Clinical trial information: NCT01392183.
Targeting bacteroides in the stool microbiome and response to treatment (Rx) with first-line VEGFTKI in metastatic renal cell carcinoma (mRCC).
Authors: VanAlstine Sidney , Froerer Camryn , Hahn Andrew W , Gilreath Jeffrey , Agarwal Neeraj , Stenehjem David D. , Bailey Erin B. 
Published: February 2018

584 Background: Diarrhea occurs in ~50% patients with mRCC receiving VEGFTKIs, and is a common cause of VEGFTKI Rx dose reductions/delays/interruptions. Stool bacteroides level directly correlates with diarrhea in these patients on Rx with VEGFTKI (Pal SK, Clinical Cancer Research 2015, PMID:26152743). Hypothesis was that mRCC patients on incidental antibiotics (ABX) which also target stool bacteroides will have less diarrhea, leading to improved Rx compliance, and improved outcomes on VEGFTKI. Methods: A retrospective study of mRCC patients with MSKCC intermediate or poor risk mRCC on 1st line VEGFRTKIs between 2005-2017. ABX usage was categorized by ABX bacteroides sensitivity at anytime during Rx with 1st line VEGFTKI along with the total number of days on ABX. 1st line VEGFRTKI progression free survival (PFS) was assessed by Kaplan-Meier and Cox proportional hazard models. Results: 145 patients with intermediate (n = 123, 85%) or poor risk (n = 22, 15%) mRCC on a VEGFTKI were identified. ABX were prescribed incidentally in 50 (34%) patients. 18 patients were prescribed ABX with bacteroides coverage of which 13 had ABX with high sensitivity for bacteroides. The median number of days supplied of all ABX was 7 (IQR 1-15 days). The median number of days supplied of ABX with bacteroides coverage was 6 (IQR 1.5-15.5 days). The median PFS in those prescribed ABX with bacteroides sensitivity was 18 months versus 8 months in those prescribed no ABX (p = 0.067), and 9 months in those prescribed ABX without bacteroides sensitivity. Duration of bacteroides ABX coverage resulted in a hazard ratio of 0.92 (95% CI 0.83-0.99, p = 0.043) for each additional day an ABX with bacteroides coverage was prescribed compared to those with no ABX. Conclusions: In these hypothesis generating data, incidental targeting of stool bacteroides with ABX correlated with improved PFS in mRCC patients on 1st line VEGFTKIs. Data need validation. Equal contribution: SAV, CDF, AWH
Changeable prognosis and associated prognostic factors for conditional survival estimates in metastatic renal cell carcinoma patients receiving the first-line targeted therapy.
Authors: Kang Minyong , Sung Hyun Hwan , Jeon Hwang Gyun , Jeong Byong Chang , Park Se Hoon , Jeon Seong Soo , Lee Hyun Moo , Choi Han Yong , Seo Seong Il 
Published: February 2018

587 Background: Conditional survival (CS) indicates the probability that patient would survive additional periods, given that the patients has previous survivorship after diagnosis or initial treatment. Here, we aim to evaluate the CS probabilities in mRCC patients who underwent targeted therapy with tyrosine kinase inhibitors (TKI) and to identify the significant prognostic factors of the CS over time. Methods: A total of 1,498 mRCC patients receiving 1st line TKI was finally analyzed from Korean multicenter database of mRCC. Kaplan-Meier survival estimates was used to calculate overall and cancer-specific CS rates by using following formula: CS(α│β) = S(α+β)/S(β), where CS(α│β) indicates the likelihood of additional α years survivorship in the person who has already survived for β years after initial diagnosis or treatment, and S(χ) is the actual survival rate. The Cox regression analysis was used to determine the predictors of CS depended on clinicopathological features. Results: We observed that 1, 2, 3, 4, and 5-year conditional cancer-specific survival (CSS) gradually increased as patients who have all additional survivorships after initial treatment, compared to those with baseline survival estimation. Also, 1, 2, 3, 4, and 5-year conditional OS rates also increased after additional 1, 2, 3, 4, and 5 year survivorships following first-line TKI treatment. Furthermore, we found that key predictive factors of OS and CSS were changed over time in multivariate analysis. While several variables, such as BMI, histologic subtypes, pT stage, were identified as prognosticators of CSS at baseline, they were not remained as independent predictors after 1 yr survivorship. Conversely, only previous metastatectomy was determined as a key prognostic factor for conditional OS over time until 4 yr survivorship after initial TKI treatment. Conclusions: Our study offers valuable information for practical survival estimation and relevant predictive factors for patients with mRCC receiving targeted therapy.