bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of radiographic characteristics of renal cell carcinoma (RCC) brain metastases treated with vascular endothelial growth factor (VEGF)-directed therapies or radiotherapy.
Authors: Goud Ajay , DeWalt Kara , Carmichael Courtney , Hsu JoAnn , Pinnamaneni Manasvi , Pal Sumanta Kumar 
Published: February 2017

479 Background: With improvements in systemic therapy for metastatic RCC (mRCC), an increased frequency of brain metastases (BM) has been observed, perhaps owing to the central nervous system (CNS) serving as a sanctuary site. The response of BM to VEGF-directed therapies has been poorly characterized. Methods: Patients (pts) with mRCC BM were identified from an institutional database. Selection of pts was further refined to pts who had received either VEGF-directed therapy during their diagnosis with BM or radiotherapy directed to their BM. Only those pts with brain MRI straddling systemic therapy and radiotherapy were selected for analysis. Imaging studies were anonymized and transmitted to an independent radiologist for review. Descriptive statistics were applied to characterize the change in sum of long axis dimensions (SLD) in two separate groups: (1) pts treated with VEGF-directed therapy and (2) pts treated with radiotherapy. Results: Of 276 pts with mRCC in our institutional database, 34 pts with BM were identified. Of these pts, 6 pts had serial MRI assessments at timepoints straddling receipt of VEGF-directed therapy. Pts had received sunitinib (n=2), sorafenib (n=2) or bevacizumab (n=2). A further 13 pts received radiotherapy with MRI imaging straddling delivery of either stereotactic radiation therapy (SRT) and whole brain radiotherapy (WBRT). Of these 19 patients, all patients had clear cell histology, and 13 patients were male. In pts receiving VEGF-directed agents, the average change in SLD of BM was -13.8%. In pts receiving radiotherapy, the average change in SLD was -6.5% (-13.0% in pts receiving SRT and +2.0% in pts receiving WBRT). Qualitatively, greater tumor necrosis and lesser rim enhancement was observed in post-treatment scans amongst pts receiving VEGF-directed agents. Conclusions: This pilot study suggested differences in CNS response with VEGF-directed therapy and radiotherapy. Multicenter collaborations are underway to validate these results in larger series.
The impact of clinical stage on renal cell carcinoma outcomes: Implications for neoadjuvant trial design.
Authors: Ball Mark Wayne , Gorin Michael A , Pierorazio Phillip M , Hammers Hans J. , Harshman Lauren Christine , Drake Charles G. , Allaf Mohamad E 
Published: February 2017

482 Background: Outcomes for patients with RCC are reported by pathologic stage; however, determination of therapy and patient counseling are based on clinical staging. Moreover, the development of neoadjuvant therapies that may requires knowledge of clinical stage-specific outcomes for trial design. Because of a paucity of reported outcomes, we characterized pathologic upstaging, recurrence-free survival (RFS) and cancer-specific survival (CSS) by stage at our institution. Methods: Our renal mass registry was queried for patients with localized RCC who underwent extirpative surgery with from 2003-2013 stratified by clinical stage. The proportion of cases upgraded by stage were determined. Survival outcomes were analyzed using the Kaplan-Meier method. Results: A total of 2,144 cases were captured during the study period. Median follow-up was 44.5 months. Clinical to pathologic upstaging is listed in the table. The highest degree of upstaging occured in cT2 cases, with 47% of cT2a and 48% of cT2b upstaged to ≥cT3a. RFS at 60 months for cT1a was 98.4%, cT1b 95.5%, cT2a 78.4%, cT2b 74.4%, cT3a 68.0%, cT3b 63.5%, cT3c 27.8%. CSS at 60 months for cT1a was 99.3%, cT1b 96.3%, cT2a 82.7%, cT2b 81.7%, cT3a 88.7%, cT3b 66.8%, and cT3c 76.9%. Harrell's C index for CSS was similar for both clinical (0.68) and pathologic stage (0.75). Conclusions: While the rate of upstaging increases markedly with increasing clinical stage, survival models based on clinical stage perform as well as those based on pathologic staging. The high rate of upstaging in cT2 disease supports enrollment of these patients in adjuvant clinical trials. Knowledge of these clinical stage-specific outcomes may be helpful for trial design. [Table: see text]
Five-year survival analysis of interferon-a plus sorafenib versus sorafenib monotherapy as first-line treatment for metastatic clear cell renal cell carcinoma.
Authors: Ding-Wei Ye , Hai-Lang Zhang 
Published: February 2017

486 Background: We compared the short- and long-term efficacy and safety of interferon-a plus sorafenib with sorafenib monotherapy as first-line treatment in metastatic clear cell renal cell carcinoma (mRCC) patients. Methods: mRCC patients who had not received systemic treatment were administered either interferon-a (300 MIU IM every other day) plus sorafenib (400 mg bid n=24, Group A) or sorafenib monotherapy (400 mg bid; n=24, Group B). Objective responses (OR; RECIST criterion ver 1.0) and differences in OR, progression-free survival (PFS), overall survival (OS) and toxicity were compared. Results: Sixty eight percent males were present in both the groups with comparable baseline demographic characteristics. After a median follow-up of 68 months, the OR was comparable (p=0.726) in Group A vs B; complete remission (1 vs 0 cases), partial remission (6 vs 7 cases), stable disease (14 vs 15 cases), and progressive disease (3 vs 3 cases). No significant difference was observed in the median PFS (p=0.965) and median OS (p=0.223) between both groups [9.4 months (95% CI: 5.8-17.4), Group A vs 14.0 months (95% CI: 9.9-18.0), Group B] and [32.9 months (95% CI: 8.2-87.1), Group A vs 20.4 months (95% CI: 16.2-24.6), Group B], respectively. The 5-year survival rate was higher in Group A vs B (46% vs 25%). Toxicity symptoms like fever (13 vs 3 cases), fatigue (15 vs 9 cases) and neutropenia (6 vs 1 cases) were more pronounced in Group A vs B. The incidence of hand and foot skin reactions, alopecia, rash, hypertension, liver dysfunction, hypophosphatemia, anemia, and other toxicities was similar in both groups. There were 14 (58.3%) and 8 (33.3%) cases of dosage reduction or suspension in Groups A and B, respectively. Conclusions: Short-term effect of interferon-a plus sorafenib as first-line treatment for mRCC was comparable to sorafenib monotherapy in terms of OR and PFS. Although higher toxicity was reported for interferon-a plus sorafenib, the combination holds promise for improving long-term OS.
Efficacy of everolimus in poor risk patients: Result of the POORTOR study.
Authors: Escudier Bernard J. , Abadie-Lacourtoisie Sophie , Blanc Ellen , Guillot Aline , Priou Frank , Mahammedi Hakim , Thiery-Vuillemin Antoine , Geoffrois Lionel , Tubiana-Mathieu Nicole , Adenis Antoine , Ferlay Celine , Albiges Laurence 
Published: February 2017

488 Background: Temsirolimus is currently the standard of care for poor risk RCC, based on the pivotal trial. Whether everolimus could be an alternative for such patients (pts) remain unknown. Methods: POORTOR is a prospective phase II study evaluating everolimus (10 mg daily) as first line therapy in RCC pts with at least 3 poor prognostic factors (IK <80%, LDH >1.5 NV, hemoglobin <NV, corrected calcium >NV, time from diagnosis to treatment <1 year and more than one metastatic site. The primary endpoint was the 1-year overall survival (OS) rate. The sample size was calculated using a Simon’s two-stage Minimax design, with the following hypotheses: p0=40%, p1=54% (based on a 47% 1-year OS in the temsirolimus arm, NEJM 2007), an 8% one-sided alpha and a 90% power. Ninety-two (92) patients (pts) were needed with an interim analysis planned after 61 pts. Results: 62 pts have been enrolled in the first stage: median age 67, men 74%, clear cell 82.3%, nephrectomy 50%. 71% pts had IK <80%, 77% pts had more than one metastatic sites, and 90% pts had a time from diagnosis to treatment <1 year. All pts had at least 3 poor risk factors: 3 = 16.4 = 26. 5-6 = 20. Six pts had a partial response by investigator assessment. With a median follow up of 16.2 m, median PFS was 3.9 m (IC95%=[2.4;5.5]) and median OS was 6.0 m (IC95%=[4.2;8.6]). One-year OS rate was 29% (IC95%[19 \;42]) which resulted in premature stop of the study at the first step. SAE were reported in 22/62 pts (35.5%).Grade 3-4 AE related to everolimus were reported in 27/62 pts (43.5%). Dose reduction of everolimus was performed in 24 pts. Conclusions: This study confirms that poor risk patients still have a very short survival in RCC. Based on these results, everolimus is not a good option for this group of pts. However, our study population had a poorer prognosis compared to the temsirolimus arm of the Hudes et al. study, partly explaining the difference in OS between the 2 studies. Clinical trial information: NCT01888042.
Potential synergistic effects of bisphosphonates with sorafenib on renal cell carcinoma with bone metastases.
Authors: Ding-Wei Ye , Hai-Lang Zhang 
Published: February 2017

496 Background: We evaluated the role of bisphosphonates in conjunction with sorafenib in improving progression-free survival (PFS) and overall survival (OS) in bone metastatic renal cell carcinoma (mRCC) patients. Methods: A total of 81 sorafenib-treated patients were retrospectively divided into 3 groups at our single study center: Group 1 (n=26, sorafenib single agent); Group 2 (n=26, sorafenib plus oral Bonefos); Group 3 (n=29, sorafenib plus intravenous zoledronic acid). Alkaline phosphatase (ALP) before and 12 weeks after treatment were evaluated as prognostic factor for PFS and OS. Results: The majority of the patients were males (67.9%) with mean age of 57.2 ± 11.2 years. Baseline demographic characteristics were similar across the 3 study groups, and the known prognostic factors were balanced across the cohort. There was no significant difference observed in the objective response between the 3 study groups (Group 1 vs. 2 vs. 3; p=0.659); partial remission (8% vs. 8% vs. 10%), stable disease (65% vs. 80% vs. 66%), progressive disease (27% vs. 12% vs. 24%). Median PFS was significantly higher in Group 2 vs 1 vs 2 (18.7 vs. 6.7 vs. 10.5 months; p=0.024). Median OS was 16.8, 22.1, and 20.7 months; p=0.052 in Group 1, 2 and 3, respectively. Multivariate analysis demonstrated that bisphosphonate use (hazard ratio [HR]=0.36, p=0.006), Memorial Sloan Kettering Cancer Center (MSKCC) score (HR=4.10, p<0.001), non-clear cell subtype (HR=1.26, p=0.039), and elevated ALP after 12 weeks’ treatment (HR=3.53, p<0.001) were associated with PFS. MSKCC score (HR=5.24, p<0.001), elevated ALP after 12 weeks’ treatment (HR=4.71, p<0.001), and metastatic organs (HR=1.93, p=0.008) were associated with OS. Bisphosphonates use was not an independent predictor of OS (HR=0.55, p=0.160). Conclusions: Bisphosphonates administered with sorafenib could synergistically improve PFS and OS in RCC with bone metastases, with the benefit of being more efficacious and safer than intravenous zoledronic acid. Elevated ALP following the treatment could be an independent predictor for both PFS and OS in bone mRCC.
Treatment-related deterioration of renal function as a biomarker to predict antitumor efficacy of sunitinib in patients with metastatic renal cell carcinoma.
Authors: Fukuda Hironori , Kondo Tsunenori , Omae Kenji , Takagi Toshio , Tanabe Kazunari 
Published: February 2017

502 Background: Some on-target adverse events such as hypertension or thrombocytopenia have been reported as biomarkers predicting the efficacy of sunitinib as first-line therapy for patients with metastatic renal cell carcinoma (mRCC). Decrease of renal function is a major adverse event of sunitinib. However, it remains unclear whether the degree of deterioration of renal function can predict the anti-tumor efficacy of sunitinib. We investigated the relationship between treatment-related deterioration of renal function and anti-tumor efficacy in mRCC patients treated with sunitinib. Methods: We retrospectively reviewed the medical records of mRCC patients who were treated with sunitinib for more than 3 months. Patients receiving hemodialysis before receiving sunitinib as well as those who did not undergo nephrectomy were excluded from our analysis. Renal function was evaluated by the estimated glomerular filtration rate (eGFR) calculated using the MDRD equation modified for Japanese patients. The degree of deterioration in eGFR was compared with progression-free survival (PFS). Results: Sixty-two patients were enrolled, the median age was 65 years, and 44 patients (71%) were male. The median baseline eGFR was 49.1 ml/min/1.73m2, and median decrease of eGFR was 9.9 ml/min/1.73m2. Forty-seven patients (76%) had a decreased eGFR of more than 10% compared to baseline values. The patients showing this decrease had significantly longer PFS than those who did not (PFS: 15.5 months vs. 6.1 months, respectively; p=0.001). On multivariate analysis, a decrease in eGFR of more than 10% was a significant independent factor for predicting longer PFS (hazard ratio, 0.37; 95% confidence interval, 0.17-0.83; p=0.017) as well as MSKCC risk groups and cycles of sunitinib. Conclusions: Treatment-related deterioration of renal function is a biomarker to predict better treatment efficacy for use of sunitinib during first-line therapy for patients with mRCC.
Long-term survivorship in patients with metastatic renal cell cancer (mRCC) managed with metastasectomy: A retrospective study from the MD Anderson Cancer Center (MDACC).
Authors: Shah Amishi Yogesh , Campbell Matthew T. , Nautiyal Kirtan Das , Hashemi Neda , Matin Surena F. , Vaporciyan Ara A. , Rhines Laurence D , Moon Bryan , Lewis Valerae O. , Lin Patrick P. , Prabhu Sujit S. , Rao Ganesh , Corn Paul Gettys , Pagliaro Lance C. , Mehran Reza J. , Wood Christopher G. , Jonasch Eric , Tannir Nizar M. 
Published: February 2017

504 Background: Overall survival (OS) in mRCC has improved with targeted therapy; however, metastasectomy is still an important tool in select patients. This study evaluated outcomes of patients managed with metastasectomy ± systemic therapies. Methods: After IRB approval, we retrospectively reviewed records of mRCC patients who were treated at MDACC between 1/1/2001 and 12/31/2008 and report on those who survived >4 years with metastatic disease. OS was calculated from diagnosis of metastatic disease to death or last follow-up. Descriptive statistics were used. Results: 168 long-term survivors were identified; 101 patients were treated with metastasectomy at some point (total 205 resections). 42 patients had single metastasectomy; 59 had multiple resections (most common in lung and bone). 12 patients underwent serial metastasectomy alone (no systemic therapy), and 8 remain alive (range 4.6-12.9 years from met diagnosis). Conclusions: Patients with mRCC selected for metastasectomy had a significantly longer OS than those who received systemic therapies only. Whether this reflects tumor biology, therapeutic effect, or selection bias is unknown in this retrospective study. However, the prolonged survival in this group supports continued use of metastasectomy in carefully selected patients. [Table: see text] [Table: see text] [Table: see text]
Comprehensive evaluation of the clinical utility of transperineal template guided mapping biopsy of prostate in the era of magnetic resonance imaging.
Authors: Sivaraman Arjun , Sanchez-Salas Rafael , Barret Eric , Galiano Marc , Rozet Francois , Prapotnich Dominic , Cathala Nathalia , Mombet Annick , Uriburu Facundo , Carneiro Arie , Cathelineau Xavier 
Published: February 2017

55 Background: To evaluate the clinical utility of Transperineal Template guided Mapping Biopsy (TTMB) after the routine use of Magnetic Resonance Imaging (MRI) for prostate cancer in our institution. Methods: We retrospectively analyzed 208 TTMB performed at our institution from April 2013 - August 2014. Anterior cancer defined as ≥ 80% of the positive cores anterior to urethra. Clinically significant cancer detection verified at various thresholds of Maximum Cancer Core Length (MCL) – 2mm / 3mm / 4mm / 6mm ± Gleason score (GS) ≥ 3+4. We analyzed TTMB for the indications, cancer detection and correlation with TRUS, MRI and Radical Prostatectomy (RP) specimens. Results: The indications and cancer detection rates of TTMB are in the table. All the patients had MRI before TTMB and 87.7% had it prior to the initial TRUS and all target biopsies were by cognitive registration. Multivariate analysis showed higher number of TTMB cores and prior negative TRUS to predict detection of clinically significant anterior tumor. The laterality of cancer in TTMB correlated with TRUS, MRI and Radical Prostatectomy (RP) in 67.2%, 75.3% and 87.6% respectively. The Gleason upgrade from TRUS to TTMB was 19.2% and TTMB to RP was 14.8%.Clavien-Dindo grade 1 and 2 complication was noted in 40.2% and 7% patients respectively. Conclusions: Even with the routine of MRI prior to TRUS biopsy, TTMB had clinical utility and was very effective in detecting clinically significant cancers in specific clinical situations. [Table: see text]
Predictors of pathological upgrading and upstaging in patients eligible for active surveillance submitted to radical prostatectomy (RARP).
Authors: Autran-Gomez Ana Maria , Secin Fernando P. , Sivaraman Arjun , Sanchez-Salas Rafael , Monzo Juan I , Prapotnich Dominic , Barret Eric , Rozet Francois , Galiano Marc , Mombet Annick , Cathala Nathalia , Cathelineau Xavier 
Published: February 2017

59 Background: To evaluate the pathological outcomes in patients who were suitable for Active Surveilance (AS) and underwent Radical Prostatectomy (RP) and to explore the potential predictive factors to identify Gleason upgrading and upstaging. Methods: A prospectively maintained database was used to evaluate 1,552 consecutive patients who underwent RP [Laparoscopic / Robotic] at our institution between 1998 and 2012. We identified 405 RP patients fulfilling the Memorial Sloan-Kettering Cancer Center criteria for AS (PSA ≤10 ng/ml, clinical stage ≤2a, Gleason≤6, ≤2 + cores and less 50% cancer in any one core). In the final RP specimen, upgrading was defined as identification of Gleason >6 and upstaging as presence of ≥ pT3. The clinical and the pathological features of upstaged/upgraded patients were compared with the remaining patients and the cox’s regression model was applied to identify potential predictors. Kaplan Meir curve was used to identify Biochemical Recurrence Free Survival (BCR-FS) at 5 years. Results: We noticed upstaging in 195 (48%) patients and Gleason upgrading in 55 (13%) at RP specimen. Multivariate analysis showed percent of positive core had significant association with upstaging/upgrading. Positive Surgical Margin (PSM) was noted in 66(16%) patients, and the PSM rate was significantly higher in upstaged patients. The mean follow-up of the study population was 28 months and the predicted BCR-FS at 5 years was 92% and 88% in the patients who were not and were upstaged/upgraded. Conclusions: Percentage of positive cores in patients subjected to Active Surveillance appears to predict pathological upstaging/upgrading at radical prostatectomy. [Table: see text]
PATRIOT Trial: Randomized phase II study of prostate stereotactic body radiotherapy comparing 11 versus 29 days overall treatment time.
Authors: Quon Harvey Charles , Ong Aldrich , Cheung Patrick , Chu William , Chung Hans T. , Vesprini Danny , Chowdhury Amit , Panjwani Dilip , Pang Geordi , Korol Renee , Davidson Melanie , Ravi Ananth , McCurdy Boyd , Zhang Liying , Bucher Oliver , Mamedov Alexandre , Deabreu Andrea , Lylyk Elizabeth , Loblaw D. Andrew 
Published: February 2017

6 Background: Stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer is rapidly increasing. Reported regimens differ in time, dose, and fractionation. We report the results of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL) and toxicity. Methods: Men with cT1-2b, Gleason <=7, and PSA <= 20 ng/mL prostate cancer were randomly assigned to 40 Gy in 5 fractions delivered every other day (11 days) vs. once per week (29 days) using gantry-based SBRT. QOL was assessed using the Expanded Prostate Cancer Index Composite (EPIC) at baseline, weeks 2, 4, 6, 12, months 6 and 12, then annually. Toxicity was graded according to RTOG Criteria. The primary end point was the proportion of patients with a minimum clinically important change (MCIC) in bowel QOL at any time during the acute (<=12 week) period and was analyzed by Fisher’s exact test with a two-sided p < 0.05 considered significant. MCIC was defined as a decrease in EPIC score of >0.5 standard deviation of the baseline value. ClinicalTrials.gov NCT01423474. Results: 152 men from 3 centres were randomized with a median follow-up of 13.1 months. Baseline characteristics were similar in both arms except for the International Prostate Symptom Score with medians of 4 vs. 7 in the 11 and 29 day groups, respectively (p=0.02). There were significant differences between the 11 and 29 day groups in the proportion of patients with acute MCIC in bowel (90.0% vs. 69.6%, p<0.01) and urinary (95.7% vs. 74.6%, p<0.01) scores, respectively. No differences were found in acute sexual (p=0.38) or hormonal (p=0.48) QOL. Worst acute grade 1, 2, 3 toxicities were 64, 18, 0% vs. 41, 11, 0% (p<0.01) for GI and 38, 32, 1% vs. 30, 34, 3% (p=0.69) for GU in the 11 and 29 day groups, respectively. There were no late grade 3+ GI toxicities. Late grade 3 GU toxicity occurred in 1 vs. 0 patients in the 11 and 29 day arms (p=0.32). Conclusions: Prostate SBRT delivered over 29 days was associated with superior bowel and urinary QOL compared to 11 days in the first 3 months of treatment. There were few severe (grade 3+) toxicities in either group. Follow-up is continuing to compare long-term outcomes. Clinical trial information: NCT01423474.