bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial and gender disparities in renal cell carcinoma.
Authors: Mozayen Mohammad , Tesfaye Anteneh , Katato Khalil 
Published: February 2017

461 Background: In spite of advancements in early diagnoses and better cancer treatments in the United States, ethnic and gender disparities still exist. In some types of cancer, African Americans and males generally tend to have higher disease frequency and worse outcomes. Studies about survival outcome among various racial groups in RCC are very scarce. Our study compared stage distribution and overall survival in relation to ethnicity and gender in patients with renal cell carcinoma (RCC). Methods: We retrospectively reviewed 205 patients diagnosed with RCC between 1995 and 2008 in a community hospital setting. Patients with additional malignancies, lymphoma of the kidneys, or no follow up data were excluded from the study. Demographics, pathology, disease stage, operative note, and subsequent follow up data were reviewed. Patients were divided into groups according to race and gender. Results: A total of 205 patients were included, Caucasians were 176 (85.9%), African Americans were 13.7% and Asians were 1 (0.5%). Males (M) were 127 (62.3%) and females (F) were 77 (37.7%). The median age of the study population was 65 (22-91). Clear cell histology was seen in 79%. Stage I was seen in 53.9%, II in 23.5%, III in 13.7% and IV in 8.8% of the study population. Advanced stages (III, IV) were seen in 18% of African American and in 23% of Caucasians (p=0.45). Advanced disease (III, IV) was seen in 22% of Females compared to 24% in Males (p=0.6). The 3 year overall survival for the study population was 67.3% (95% CI: 60.4-73.7). The 3 year overall survival for African Americans was 50% compared 71.5% in Caucasians (p=0.02). The 3 year overall survival for Females was 68.4% compared to (68.8%) (p=0.54). Conclusions: Our study showed that in patients with RCC, African Americans had worse survival outcome compared to Caucasians in spite of similar stage distribution. Our study didn’t show any gender based disparity in overall survival. Large studies are necessary to determine the causes of poor survival outcome in African American population in RCC.
Korean population-based external validation of western prognostic models for survival in metastatic renal cell cancer.
Authors: Ahn Yongchel , Park Kwonoh , Park Seongjoon , Park Inkeun , Lee Jae-Lyun , Song Cheryn , Ahn Jin-Hee , Hong Jun Hyuk , Kim Choung-Soo , Ahn Hanjong 
Published: February 2017

464 Background: Prognostic models have been proposed to predict factors affecting survival in metastatic renal cell cancer (RCC). We retrospectively reviewed clinical features and survival data to validate MSKCC and Heng’s models in Korean metastatic RCC patients. Methods: 270 patients with first-line Vascular Endothelial Growth Factor (VEGF) targeted therapy, regardless of prior immunotherapy, were enrolled. We reviewed medical records to find clinical factors affecting overall survival (OS). Predictive accuracy for survival of two models was evaluated by Harrell’s concordance-index (c-index). Results: From 2005 to 2010, 197 males (72.6%) and 73 females received therapy at a median age of 58 years (range, 17 - 86). After median follow-up of 16.0 months (range 0.0 - 78.0), median OS (mOS) was 22.7 months (95% CI, 18.3 - 27.1). 55 patients (20.4%) had prior immune therapies and 162 (60.4%) were initially metastatic. None was treated with bevacizumab, thus 221 (81.9%) were treated with sunitinib and 49 with sorafenib. Multivariate analysis showed 5 of Heng’s factors were independent: Karnofsky scale < 80% (HR = 1.53, 95% CI 1.01 - 2.31, p=0.047), from diagnosis to treatment < 1 year (HR=1.94, 95% CI 1.35 - 2.79, p < 0.001), anemia (HR 1.66, 95% CI 1.13 - 2.43, p = 0.010), hypercalcemia (HR = 1.92, 95% CI 1.21 - 3.05, p=0.006) and neutrophilia (HR = 1.96, 95% CI 1.21 - 3.16, p = 0.006). Validation of MSKCC and Heng’s model showed c-index of 0.836 (95% CI, 0.698 - 0.941) and 0.800 (95% CI, 0.655 - 0.915), each. We further applied each model’s stratification by risk grouping. First with MSKCC (log-rank p < 0.001), mOS in no risk (n = 80), 1 risk (n = 128) and 2 or more risks (n=51) were 35.5 months (95% CI, 24.0 - 47.0), 23.7 months (95% CI, 18.2 - 29.2) and 7.4 months (95% CI, 4.5 - 10.3), respectively. Second with Heng’s (log-rank p < 0.001), mOS in favorable (no adverse factors, n = 37), intermediate (one or two adverse factors, n = 161) and poor (three to six adverse factors, n=61) were respectively 43.8 months (95% CI, 31.8 - 55.8), 25.4 months (95% CI, 21.5 - 29.3) and 7.5 months (95% CI, 4.9 - 10.1). Conclusions: Western prognostic models were accurate and feasible in Korean metastatic RCC patients treated with anti-VEGF therapy.
Metastatic renal cell carcinoma (mRCC) in elderly patients: Can a personalized approach be an effective therapeutic option?
Authors: cossu Rocca Maria , Verri Elena , Blotta Simona , Adamoli Laura , Radice Davide , Riva Davide Francesco , Nole Franco 
Published: February 2017

468 Background: Renal cell carcinoma (RCC) is the third most common genitourinary cancer. Up to 30% of patients (pts) with RCC presents with advanced disease. Sunitinib(S), an orally available tyrosine kinase inhibitor, is the well established first-line therapy for these population. Actually few data are available in the literature about its use in patients > 75 yrs investigating the feasibility, the efficacy and the toxicity in this population. Methods: From 2007 to 2011, 16 pts >75 yrs with mRCC received S. 75% of pts had a clear cell carcinoma, 87.5% had a surgery on primary tumor, 18.7% had a metastic disease at diagnosis and the median time to metastatic progression was 13.5 months. Median age was 78 years (range 71-88y).All patients had 0-1 performance status and 69% of them received S as first-line treatment. Four pts started S on the approved 50 mg /d 4-week-on-2-off schedule, but three of them reduced to 37.5 mg continuous once daily dosing(ODD)starting from the third cycle. Five out of 8 pts receiving 37.5 mg continuous ODD reduced the dose at 25 mg continuous ODD or modified the schedule. Four pts started with 25 mg continuous ODD and 2 of them continued the treatment at modified schedule. Median number of cycles administered was 7 (range 2-16). Results: Response rate was 87% (13pts) in 15 evaluable pts. Overall response included 40% (6 pts) of PR, 20% (3pts) of CR, 33% (5pts) of SD > 6 mos. Progressive disease was observed only in 1patient. TTP was 12.4 months (95% CI, 4.8-32.6). Overall survival was 34.2 months (95% CI, 27.3- ). The main toxicity requiring dose reduction or schedule modification was haematological (46%), G3Anemia in 1 pt G3-4 thrombocytopenia in 3pts and G3 leukoneutrophenia in 3pts. No any toxicity required treatment interruption. Conclusions: In summary these results show the feasibility and the efficacy of S in elderly population with high response rate regardless the doses and schedule used.
A new modified sunitinib schedule for metastatic renal cell cancer (mRCC): A pilot study.
Authors: Buti Sebastiano , Donini Maddalena , Lazzarelli Silvia , Brighenti Matteo , Passalacqua Rodolfo 
Published: February 2017

471 Background: Oral sunitinib administration at 50 mg daily given for 4 weeks followed by 2 weeks off treatment (4+2 schedule) is a standard first line for mRCC treatment. About 20% of patients had to discontinue treatment permanently and 50% of patients are forced to reduce the doses due to adverse events [Motzer RJ, J Clin Oncol. 2009]. A meta-analysis showed that increase exposure to sunitinib is associated with improved clinical outcome [Houk BE, Cancer Chemother Pharmacol. 2010]. Methods: This is a pilot study in which consecutive mRCC patients admitted to our hospital who had at least a grade 2 toxicity with sunitinib, were switched to a modified schedule maintaining the same dose-intensity of 4+2 schedule: starting on Monday, 1 tablet (50 mg) a day for 5 consecutive days a week for 5 weeks and 1 tablet per day on days 1, 3 and 5 in the sixth week (28 tablets in 6 weeks), until disease progression. Primary end points were toxicity changes assessment and schedule feasibility, secondary end point was overall progression free survival (PFS). Results: Eight nephrectomized patient were enrolled: 6 males; median age 61; 37% good, 50% intermediate and 13% poor MSKCC risk; 3 patient pretreated; 6 clear cell histologies, 1 papillary and 1 undifferentiated histotypes. Median time from start therapy to switch was 7.4 months (range 1.4-16.1). Treatment delays and dose reductions were reduced from 50% to 25% and from 37% to 12% of patients respectively. The table shows the toxicity changes: there were no new toxicities. PFS was 16.3 months (CI 95% 5.6-23.4). Conclusions: This new modified schedule requires and deserves further studies. [Table: see text]
Randomized study on the effect of zoledronic acid treatment for prostate cancer with bone metastasis during initial combined androgen blockade.
Authors: Ueno Satoru , Mizokami Atsushi , Namiki Mikio , Fukagai Takashi , Fujimoto Naohiro , Ooka Hitoshi , Kondo Yukihiro , Arai Gaku , Ide Hisamitsu , Kataoka Kazuyoshi , Kawaguchi Kohei , Shimamura Masayoshi , Orito Matsuo , Ishida Takeyuki , Ikeda Daisuke 
Published: February 2017

48 Background: Zoledronic acid (ZA) eventually reduces risk of skeletal morbidity carries beneficial effect on bone pain. Moreover, ZA eventually extends a period to bone pain and the SRE onset after CRPC (castration-resistant prostate cancer) and improves the QOL of the patients. ZA, therefore, has become a standard supportive therapy for CRPC with bone metastasis. However, it remains unclear when the physicians should start ZA treatment for prostate cancer (PCa) patients with bone metastasis. In the present study, we investigated whether we could extend a period before androgen sensitive PCa with bone metastasis becoming CRPC by ZA treatment. Methods: The patients were randomly classified in two groups (combined androgen blockade (CAB) alone group and CAB + ZA treatment group) based on Gleason score (less than 7 or more) EOD score (less than 2 or more). Four mg ZA treatment was conducted every 4 weeks. We evaluated serum PSA value, bone-related markers, and SRE. The first end point was a period before androgen sensitive PCa with bone metastasis becoming CRPC. Results: Untreated 59 PCa patients with bone metastasis were enrolled by 2011 from 2006. Thirty patients were classified in the CAB alone group and 29 patients in the CAB + ZA group. There were no significant difference in age (72,5 and 71.7 yo, respectively), PSA (381.3 ng/ml and 399.0 ng/ml, respectively), Gleason score, and EOD score between CAB alone group and CAB + ZA group. Although there was no significant difference in PSA-progression free survival (PFS) (p=0.14), tendency that CAB + ZA shows better PFS than CAB alone group was observed (time to 50% PFS was extended 9.4 months than CAB alone group). Moreover, the sub analysis using the patients with more than Gleason score 7 or with more than EOD score 1, CAB +ZA group showed better PFS (p=0.074 in Gleason score and p=0.028 in EOD score. Conclusions: This result indicates that CAB with ZA from initial treatment can extend a period before PCa, especially high advanced PCa recurring.
Neutropenia as a potential pharmacodynamic marker for docetaxel-based chemotherapy in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: Pond Gregory Russell , Berry William R. , Galsky Matt D. , Wood Brian A. , Leopold Lance Howard , Sonpavde Guru 
Published: February 2017

51 Background: Data suggest docetaxel clearance is increased in castrate men. An association of docetaxel-induced grade ≥3 neutropenia with overall survival (OS) may provide a rationale for tailored dosing in mCRPC. Methods: The association of cycle 1 neutropenia with OS was examined in a randomized phase II trial of 221 men with mCRPC receiving docetaxel-prednisone combined with placebo or AT-101 (bcl-2 inhibitor), which performed weekly blood cell counts during the first cycle. Patients from both arms were combined as no outcome or neutropenia differences were observed. OS was calculated from randomization by the Kaplan-Meier method and Cox proportional hazards regression models were used to estimate the association with OS. Results: The difference in OS between men with day 8 ≥grade 3 neutropenia and those with ≤grade 2 neutropenia was significant after adjusting for stratification factors (HR: 0.64, p= 0.048). Excluding men with delayed cycle 2 yielded a more significant association of grade 3-4 neutropenia on day 8 with survival (Table). Men with ≥grade 3 neutropenia and ≥30% PSA decline by day 90 had improved OS compared with men exhibiting neither (HR: 0.51, p=0.014). Conclusions: In mCRPC receiving docetaxel, ≥grade 3 neutropenia on day 8 was prognostic for improved OS, suggesting its potential utility as a pharmacodynamic marker in this hypothesis-generating analysis. Since the association was stronger after excluding patients that experienced dose delays, grade 3 neutropenia may confer a more favorable therapeutic index than grade 4 neutropenia. The exploration of dose modulation of docetaxel to attain ≥grade 3 neutropenia on day 8 may be warranted. [Table: see text]
Use of zoledronic acid therapy–associated severe hypophosphatemia to identify poor-prognosis patients with metastatic castration-resistant prostate cancer.
Authors: Warr Julia , Yam David , Goodall Shannon , VanDraanen Leah , Giotis Angie , Pasetka Mark , De Angelis Carlo , Emmenegger Urban 
Published: February 2017

58 Background: Zoledronic acid (ZOL) therapy is associated with severe (i.e., grade 3/4 according to CTCAEv4.0) hypocalcemia and hypophosphatemia in a subset of patients with metastatic castration-resistant prostate cancer (mCRPC) to bone. However, as opposed to the distinct clinical picture of hypocalcemia, the symptoms of hypophosphatemia are less pathognomonic. Furthermore, the rate of hypophosphatemia is not regularly reported. Methods: To characterize the rate and circumstances of severe hypophosphatemia in mCRPC patients undergoing ZOL therapy, we identified mCRPC patients receiving at least 3 doses of ZOL therapy at our Centre between 2004 and 03/2011. Patient demographics, disease and laboratory parameters were extracted by using the Oncology Symptom Control and Information Resource database, and by means of manual chart review. Results: 11 of 112 patients (10%) developed grade 3/4 hypophosphatemia (nadir) after 241±223 days (mean±SD) following the first dose of ZOL. Only one patient presented with concomitant severe hypocalcemia. Interestingly, the hypophosphatemia nadir coincided with rising PSA readings in 9 out of 10 informative patients. Furthermore, ZOL-associated severe hypophosphatemia identified mCRPC patients with worse outcome (time from CRPC diagnosis to death 628±317 days, versus 901±526 days in CRPC patients without severe ZOL-associated hypophosphatemia, p < 0.028). Conclusions: 10% of mCRPC patients undergoing ZOL therapy presented with grade 3/4 hypophosphatemia. While hypocalcemia usually occurs within the first 6 months of ZOL therapy, ZOL-associated severe hypophosphatemia is a relatively late event. It appears to occur at the time of disease progression and is associated with a poor outcome.
A phase I trial of AEZS-108 (AN-152) in castration- and taxane-resistant prostate cancer.
Authors: Liu Stephen V. , Schally Andrew V , Dorff Tanya B. , Tsao-Wei Denice D. , Groshen Susan G. , Xiong Shigang , Hawes Debra , Quinn David I. , Tai Yu-Chong , Block Norman L. , Engel Juergen , Pinski Jacek K. 
Published: February 2017

60 Background: The prognosis for patients with castration-resistant prostate cancer (CRPC) remains suboptimal and targeted therapies should be explored. One potential target is the receptor for luteinizing hormone-releasing hormone (LHRH-R), which is highly expressed on prostate cancer cells. AEZS-108 (AN-152) is an LHRH-cytotoxic hybrid whose rational design covalently couples an LHRH agonist and the cytotoxic doxorubicin. AEZS-108 exploits the presence of these receptors to target delivery of the cytotoxic. We report the phase I trial of AEZS-108 in men with taxane-resistant CRPC. We also report correlative studies of a novel circulating tumor cell (CTC) capture device that will provide both enumeration of CTCs and LHRH-R expression on captured CTCs as well as results from AEZS-108 internalization studies that exploit the auto-fluorescence of doxorubicin in captured CTCs. Methods: This is a single-arm, dose-escalation phase I study in men with CRPC to confirm the dose established in a completed phase I trial in females. Eligibility criteria included adequate organ function and progression of disease despite prior therapy with an LHRH agonist and at least one taxane-based regimen. Patients were required to discontinue LHRH agonists to avoid receptor competition. Patients received AEZS-108 every 21 days until progression or unacceptable toxicity for up to 6 cycles. The primary endpoint was safety. Results: Enrollment began in November 2010 and completed in September 2011. Twelve patients were accrued onto 3 dose levels. No DLTs have been noted. At the time of submission, a decrease in PSA was noted in 5 of the 10 evaluable patients. The grade 3 or 4 toxicities were primarily hematologic. Final reports detailing toxicity, RECIST response and PSA response will be reported. All correlative studies will also be reported. Conclusions: AEZS-108 is well tolerated and has demonstrated early signs of antitumor activity in men with CRPC. We will report the recommended dose for the planned phase II study.
Modeling fecal incontinence symptoms 6 years after high-dose radiation for prostate cancer: Clinical and dosimetric predictors.
Authors: Fellin Giovanni , Rancati Tiziana , Fiorino Claudio , Vavassori Vittorio , Cagna Emanuela , Mauro FloraAnna , Malinverni Giuseppe , Valdagni Riccardo 
Published: February 2017

71 Background: To evaluate the incidence of late fecal incontinence (linc) after high-dose radiotherapy (RT) in prostate cancer patients (pts) accrued in AIROPROS 0102 trial (RT doses: 70-80Gy, 1.8-2Gy/fr) and to model the relationship between linc and clinical/dosimetric factors. Methods: Self-reported questionnaires of 515 pts with a minimum follow up of 6 yrs were analyzed with respect to linc. G1 linc was scored if unintentional stool discharge was “sometimes” experienced, G2 linc if unintentional stool discharge was “often” experienced or if pts sporadically used sanitary pads; G3 if pts reported daily unintentional stool discharge or use of sanitary pad >2 times/week. Correlation between pre-treatment morbidities, hormonal therapy, drug prescription, presence of diabetes or hypertension, abdominal surgery prior to RT (SURG), presence of G2-G3 acute fecal incontinence (ACUINC), pelvic nodes and seminal vesicles irradiation, mean rectal dose, dose-volume histograms constraints (from V20Gy to V75Gy) and linc was investigated by uni- and multivariate (MVA) logistic analyses. 347/515 pts had at least 3 toxicity questionnaires in the first 36 mos after the end of RT. Correlation between the mean score of fecal incontinence in the first 36 mos and linc at 6 yrs was also investigated. Results: 50/515 G1, 3/515 G2 and 3/515 G3 linc were reported. In MVA, V40Gy (continuous variable, p=0.09, OR=1.015), use of antihypertensives (protective factors, p=0.005, OR=0.38), SURG (p=0.004, OR=4.7), presence of haemorrhoids (p=0.008, OR=2.6) and ACUINC (p=0.007, OR=4.4) resulted to be correlated to linc. Based on MVA results, a nomogram was developed. Linc at 6 yrs was also correlated to the mean incontinence scores in the first 36 mos (p<0.0001): pts without linc at 6 yrs had a mean score of 0.1 during the first 36 mos, while pts with G1 and with G2-G3 linc at 6 yrs had a mean score of 0.5 and 0.78 during the first 36 mos, respectively. Conclusions: Mean score for incontinence during the first 36 mos after RT can be used as a surrogate endpoint for late (>6yrs) fecal incontinence. Linc is correlated to clinical and dosimetric risk factors and individualised toxicity prediction can be performed through a nomogram.
Hormonal impact of salvage chemotherapy with carboplatin plus weekly docetaxel in patients with castration- and docetaxel-resistant prostate cancer (DRPC).
Authors: Reuter Christoph W. , Morgan Michael A. , Fenner Martin , Grünwald Viktor , Ganser Arnold 
Published: February 2017

74 Background: Recent data suggest that carboplatin may be effective in combination with docetaxel in DRPC. Platinum(II)-complexes have been shown to interfere with testosterone biosynthesis by inhibiting the cholesterol side chain cleavage enzyme (CYP11A1), 3b-hydroxysteroid dehydrogenase (HSD3B1,2) and 17a hydroxylase/C17,20-lyase (CYP17A1). Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2 2007) criteria. Since February 2005, 68 consecutive DRPC pts were treated with at least two cycles of carboplatin AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG2 recommendations. Free testosterone levels were measured before (n=42) and during DC treatment (n=36). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 32/68 (47.1%) patients. At the time of the current analysis the median follow-up time was 13.6 months and 43/68 patients had died. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.4, 9.5) and median overall survival (OS) was 18.6 months (CI 95% 12.3, 24.9). In PSAR, PFS was 15.7 versus 4.8 months in PSANR (p<0.001; hazard ratio HR 0.19, CI 0.09, 0.39) and OS was 25.6 versus 8.1 months (p<0.001; HR 0.21 CI 0.10, 0.42). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (39.7/33.8%). Median free testosterone levels were 0.935 pg/ml before and 0.185 pg/ml during DC treatment (nadir; p<0.001). While free testosterone levels before DC treatment were associated with lower PSAR (HR 6.32 CI 1.60, 25,0; p=0.009), free testosterone nadir levels <0.18 pg/ml during DC treatment were associated with higher PFS (HR 0.126 CI 0.04, 0.46, p=0.002) and OS (HR 0.07 CI 0.008, 0.53; p=0.01). Conclusions: These data suggest that DC may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.