bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors and survial of advanced renal cell carcinoma with predominant sarcomatoid histology.
Authors: Park I. , Lee J. , Ahn J. , Lee D. , Song C. , Hong J. , Kim C. , Ahn H. 
Published: February 2017

400 Background: Sarcomatoid renal cell carcinoma (SRCC) is known to have aggressive clinical course and poor response to treatment. Very limited data of clinical feature, prognostic factor, and survival are available for advanced disease with predominant sarcomatoid histology. We evaluated clinical features, response to treatment, and prognostic factors for survival. Methods: Between 2001 and 2010, 30 patients with metastatic or recurrent RCC with predominant sarcomatoid histology (sarcomatoid component 30% or more for resected kidney or exclusive sarcomatoid carcinoma on needle biopsy) were treated at our institution. We reviewed these patients' records to identify clinical and pathologic features which could affect survival. The role of nephrectomy and systemic therapy on patient outcome was also investigated. Results: There were 20 male and 10 female patients with a median age of 58 years (range, 43–83). Twenty patients had initially metastatic disease and 16 patients (53%) had ECOG performance status (PS) of 0–1. The most frequent metastatic site was lung (57%) followed by bone (43%) and distant lymph nodes (23%). Fourteen (70%) out of 20 patients with initially metastatic disease underwent primary nephrectomy and six patients also underwent metastasectomy. The median % of sarcomatoid component was 80% (range, 30–100%). All patients (N=10) who received immunotherapy had progressive disease as their best response and only one out of 5 patients treated with sunitinib or everolimus had a partial response. With a median follow-up duration of 22 months, the median survival was 3.6 months (95% CI, 0∼7.5) with 6-month survival rate of 43%. Only ECOG PS had impact on survival (P<0.001: ECOG=0, 14.1 months; ECOG=1, 7.4 months; ECOG=2, 3.2 months, and ECOG=3, 1.64 months). Survivals for initially metastatic disease were not significantly different whether patients underwent nephrectomy or not (2.0 months vs. 3.4 months, HR=0.62, 95% CI, 0.16–2.44 after correcting for potential prognostic factors). Conclusions: Patients with SRCC have a fulminant clinical course and the majority of patients had disease progression irrespective of any treatment. Only performance status dose have impact on overall survival. No significant financial relationships to disclose.
Anti-VEGF drugs combined with gemcitabine-based chemotherapy in treatment of metastatic collecting duct carcinoma.
Authors: Guo J. , Cui C. L. , Chi Z. H. , Si L. 
Published: February 2017

403^ Background: Collecting duct carcinoma (CDC), accounting for less than 1% of kidney cancer, demonstrates an aggressive course and extremely poor prognosis. There are still no standard treatment regimens for this disease at present. Sunitinib and sorafenib, two protein tyrosine kinase inhibitors, have been used in treatment of renal cell carcinoma mainly by inhibiting vascular endothelial growth factor receptor (VEGFR). However, the combination of anti-VEGF drugs with gemcitabine-based chemotherapy has not been tested in CDC treatment. Methods: From Jun 2008 to Aug 2010, six patients (5 males and 1 female) with metastatic CDC, ECOG PS ≤ 2 and adequate organ function were enrolled in the trial. Four patients received sorafenib (400mg bid) and two received sunitinib (37.5mg Qd), all in combining with gemcitabine (1.0 g/m2 d1,8) and cisplatin (40 mg d1-3) Q28d. A mean of 2.3 cycles (range 1-4 cycles) was given. Performance status 0-2 was allowed. Tumor assessments and radiological evaluations were conducted every 4 weeks. Results: The median age was 41.5 years (range 28-60 years). All patients received prior nephrectomy. The sites of metastases included lung (4/6), skeleton (3/6), mediastinal lymph node (2/6), and liver (1/6). The therapy was well tolerated with grade 3-4 toxicities: neutropenia (4/6), thrombocytopenia (2/6), hand-foot syndrome (1/6) and rash (1/6). One patient had partial response, four had stable disease, and the disease control rate was 83.3% (5/6). The median progression-free survival was 3.5 months (range 1-6+ months), and the median overall survival was 6.5 months (1-15+ months) with the median follow-up of 6.5 months. No drug related deaths occurred. Conclusions: The combination of anti VEGF drugs and gemcitabine based chemotherapy are well tolerated. This treatment regimen demonstrates modest antitumor activity and may cause progression-free survial benefit in patients with CDC. [Table: see text]
Candidate biomarkers in renal cell carcinoma.
Authors: Seliger B. , Lichtenfels R. , Recktenwald C. , Dressler S. , Atkins D. , Stevanovic S. 
Published: February 2017

405 Background: Renal cell carcinoma (RCC) represents a heterogeneous disease with widely varying prognosis. Therefore, the screening for biomarkers, which allow the diagnosis as well as the assessment of the individual risk of disease progression and mortality are a prerequisite for the selection of patients for different modes of therapies and the implementation of individually tailored surveillance protocols. Methods: Various proteome-based technologies such as 2DE-based proteomics, PROTEOMEX or ligandomics in combination with mass spectrometry have been applied. Bioinformatic data mining led to the categorization and priorization of the respective target lists. Selected candidate targets were further independently verified by qRT-PCR, Western blot and/or immunohistochemistry. Results: A large series of differentially expressed/immunoreactive proteins have been identified in clear cell RCC when compared to normal kidney epithelium. With the different approaches distinct sets of potential candidate targets were defined and categorized into different protein families and functions and according to their cellular localization. Moreover, the limited sharing rates between the respective target lists demonstrate their complementarity. Some selected markers were further validated by qRT-PCR, Western blot analysis and/or immunohistochemical stainings of tissue micro arrays comprised of RCC lesions of different TNM classification and histology revealing distinct expression pattern in regard to the RCC subtype, tumor grading,staging or additional molecular features. Using the ligandomics approach proteins have been identified, which were able to mount an immune response in vitro. Conclusions: Some candidate markers might have the potential to be used as diagnostic and prognostic factors if not as novel targets for therapy and thus could be employed for the expression profiling of a larger series of RCC patients. No significant financial relationships to disclose.
Prognostic impact of post-prostatectomy PSA slope determined with a novel, nucleic acid detection immunoassay (NADiA ProsVue) for total PSA.
Authors: Moul J. W. , Semmes O. J. , Vessella R. , McDermed J. E. , Lilja H. 
Published: February 2017

47 Background: ProsVue is an investigational PSA immunoassay whose reporter antibody is labeled with a synthetic DNA sequence. RT-PCR detects the DNA signal indicating the PSA concentration. Pilot studies showed ProsVue slope (least-squares linear slope of 3 post-RP PSA values) to correctly classify prostate cancer (PC) patients (pts) with no evidence of disease (NED) and clinical progression (CP) using a 2 pg/mL/month (mo) decision threshold. In a retrospective, multicenter clinical trial, we evaluated potential prognostic value of ProsVue slope at this decision threshold. Methods: 392 PC pts having RPs 11/1991 to 8/2001 were studied. Eligibility required first post-RP PSA <100 pg/mL, full pathologic and radiographic data and 3 frozen serum samples drawn 6 weeks to 19.4 mo post-RP. Adjuvant radiotherapy (RT) and/or hormone therapy (HT) was not allowed. CP was documented by positive imaging, biopsy results or PC-related death. Efficacy of ProsVue slope as a prognostic test for NED/CP at a 2 pg/mL/month decision threshold was determined and also examined with regards to Gleason score (GS), pre-RP PSA and final pathology stage. Results: Median (range) of pre-RP PSA was 6.3 (0-60.6) ng/mL and post-RP GS was 7.0 (4-10). 73 pts received neoadjuvant HT. Pathologic stage was pT0-2 (228), pT3 (147), pT4 (17); 116 pts had positive margins and 8 had positive lymph nodes. The 3 PSA values were drawn after a median of 4.9, 8.6 and 12.8 mo and showed median values of 10.7, 23.0 and 50.7 pg/mL, respectively. Calculated sensitivity, specificity, PPV and NPV for a 2 pg/mL/mo ProsVue slope were 75.0%, 96.6%, 81.4% and 95.2%, respectively. Median follow-up (f/u) was 10.5 years. There were 40 deaths (14 from PC). Conclusions: ProsVue provides information previously unknown in post-RP pts. ProsVue slope ≤2pg/mL/mo in the first year is highly associated with NED over long-term f/u. Potential clinical utility may include predicting pts not requiring long-term oncologic f/u and predicting a need for post-RP adjuvant RT. ProsVue slope may become a new paradigm for identifying those patients at reduced risk for recurrence of prostate cancer post-RP. Further studies are planned to address these questions. [Table: see text]
Use of speed and extent of PSA response during the first three cycles of docetaxel chemotherapy in metastatic castrate-resistant prostate cancer to predict overall survival.
Authors: Goody R. B. , Mitchell D. M. , McAleese J. , O'Sullivan J. M. 
Published: February 2017

48 Background: Docetaxel chemotherapy has an established role in the management of metastatic castrate-resistant prostate carcinoma (CRPC). With an overall survival benefit demonstrated with second line agents, identifying non-responders to docetaxel at an early stage would allow timely consideration of therapy change.We wished to assess PSA response rates to sequential cycles of docetaxel chemotherapy to determine after which cycle men should be considered nonresponders.We also wished to assess if previous therapy with diethylstilbestrol (DES) influenced subsequent response to docetaxel. Methods: Retrospective case review of all men with CRPC receiving docetaxel chemotherapy between January 2007 and April 2010 at our institution was performed. PSA immediately prior to cycle 1 (baseline) and subsequent cycles were noted and evaluated for response compared to baseline PSA. Results: 86 men with a median age of 65 years (47-81) received an average of 5 cycles (1-10) of docetaxel chemotherapy. 67 (77%) had a documented fall in PSA below baseline during chemotherapy with 56 (65%) and 43 (50%) having a PSA response of >30% and >50% respectively. A PSA level lower than baseline was seen in 54%, 63% and 72% of men after cycles 1, 2 and 3 respectively. Limited PSA falls below baseline were seen in 3 (3.4%) and 2 (2.3%) men after cycles 4 and 5 respectively. All PSA responses of >50% had occurred by the start of cycle 4. Of the 14 men who had received DES prior to starting docetaxel, only 3 (21%) had >50% reduction in PSA. The median overall survival for men achieving a PSA response >50% below baseline was 20 mths and was significantly better than the median overall survival of 10mths for those with no PSA response >50% (p<0.0001). Site of metastatic disease also correlated with survival. Conclusions: In our population, men who fail to document a PSA response to the first 3 cycles of docetaxel chemotherapy are highly unlikely to do so after this time. Response defined as a fall below baseline and the extent of PSA decline below baseline are all correlated with survival. More modest PSA responses are seen in men pre-treated with DES than those who have not received DES. No significant financial relationships to disclose.
Prostate cancer outcomes and polymorphism in LHRH and LH receptors and SHBG.
Authors: Liu S. , Pinski J. K. , Ingles S. A. 
Published: February 2017

5 Background: The hypothalamic-pituitary-gonadal axis is integral to androgen synthesis and the management of prostate cancer (PC). Genetic variation in the receptors of this pathway may impact the efficiency of signal transduction and overall clinical course. We examined polymorphisms in four receptors central to this pathway: luteinizing hormone-releasing hormone receptor (LHRHR), luteinizing hormone receptor (LHR), androgen receptor (AR) and steroid hormone binding globulin (SHBG). We examined the association between these genotypes and survival. Methods: Patients diagnosed with PC between 1999 and 2004 in Los Angeles County were identified using the Los Angeles County Cancer Registry as part of the California Collaborative Prostate Cancer study, a multiethnic, population based case-control study. Included in this analysis were 1232 men with PC: 631 with advanced stage PC at diagnosis and 430 with high-grade PC. The ethnic breakdown was 376 African-American, 355 Hispanic and 501 Caucasian. DNA was extracted from blood and genotypes for LHR, LHRHR, AR and SHBG were assayed using TaqMan or GeneScan methods. Vital status and cause of death was obtained by linking to the Cancer Registry records. Hazard ratios were estimated by fitting Cox proportional hazards models. Results: As of September 2010, 396 (32%) had died and 122 (10%) had died of PC. In the multivariate model, there was a significant association between disease specific survival and genetic variation in LHRHR, LHR and SHBG. Hazard ratios (HR) for carriers (vs. non-carriers) of the LHR312 minor allele were 1.63 (95% CI: 1.08-2.45) among all cases and 2.04 (1.23-3.39) for high- grade cases. The LHRHR16 minor allele was rare among African Americans; the HR among Caucasians was 1.90 (1.15-3.13) and did not vary by disease grade. The SHGB356 minor allele was associated with survival only among high-grade cases with a HR of 2.38 (1.18-4.81). In addition, when comparing cases to controls, the LHR312 minor allele was inversely associated with PC incidence. Conclusions: Genetic variation in the LHRHR, LHR and SHGB genes are associated with PC survival and warrant further analysis to define their role as prognostic and predictive markers. No significant financial relationships to disclose.
Gastrointestinal toxicities following radiation therapy for localized prostate cancer.
Authors: Lu-Yao G. L. , Kim S. , Moore D. , Shih W. , Lin Y. , Shen S. , Li H. , Dolan M. , Shao Y. 
Published: February 2017

64 Background: Radiation therapy (RAD) is commonly employed to treat localized prostate cancer; however, representative data regarding treatment related toxicities compared to conservative management (CM) is sparse. Methods: We performed a population-based cohort study, using Medicare claims data linked to the Surveillance, Epidemiology, and End Results data, to evaluate gastrointestinal (GI) toxicities in men aged 65-85 years treated with either primary RAD or CM for T1-T2 prostate cancer diagnosed in 1992-2005. In this study, only GI toxicities requiring interventional procedures occurring after 6 months of cancer diagnosis were included. Competing risk models were used with the following covariates: year of diagnosis, comorbidity, age, tumor stage, cancer grade, hormone use within 1 year of diagnosis, region, race, poverty and marital status. Results: Among 41,859 patients in this study, 28,021 patients received radiation therapy, 19,287 with external beam radiation therapy (EBRT) alone, and 5,138 with brachytherapy alone. The most common GI toxicity was GI bleeding or ulceration. GI toxicity rates were 6.1% after 3D-conformal therapy (3D-CRT), 2.8% after intensity modulated radiation therapy (IMRT), 2.6% after brachytherapy, 8.2% after proton therapy and 1.1% for CM patients. In the multivariate models, RAD group was associated with a higher hazard of GI toxicities (hazard ratio [HR] 4.68; 95% CI, 3, 93-5.58) than CM. Comparing to 3D-CRT, brachytherapy (HR 0.62; 95% CI, 0.51-0.75) and IMRT (HR 0.67; 95% CI, 0.55-0.82) are associated with a lower hazard of GI toxicities, while proton therapy is associated with a higher hazard of GI toxicities (HR 2.15; 95% CI, 1.45-3.17). Conclusions: Radiation therapy is associated with a higher risk of GI toxicities than CM. Among different modalities of radiation therapy, protons therapy is associated with the highest risk of GI toxicities, followed by 3D-CRT, IMRT, and brachytherapy. The increased GI toxicities for patients with proton therapy may reflect a learning curve in the early years. No significant financial relationships to disclose.
Radiation oncologist density and prostate cancer mortality.
Authors: Aneja S. , Yu J. B. 
Published: February 2017

72 Background: There exists a geographic variation among the distribution of radiation oncologists (RO). The goal of this study was to determine the effect of RO density (ROD) on prostate cancer (PC) mortality (PCM). Methods: Using county- level data from the 2008 Area Resource File, National Program for Cancer Registries, and US Centers for Disease Control, a multivariate regression model was constructed for PCM, controlling for county-level categorized ROD, demographics, socioeconomic status, and existing hospital facilities. Urologist and allergy/immunology density (UD and AID) were explored to assess whether the association with PCM was due to differences in regions with high medical specialist density or whether it was due to access to PC specific specialists. Results: There was a statistically significant reduction in PCM (reduction ranging from 9% to 29% p<.001) associated with counties that possessed at least 1 RO. Moreover, increasing the county density to greater than 2 ROs per 100,000 people had a statistical significant reduction in PCM compared to having one RO (p<.001). UD and AID were also associated with a reduction in PCM. Conclusions: The presence of a RO is associated with lowered PCM within that county, and increasing ROD does yield further improvements in PCM. Whether access to specialized medical care is an indicator of available health resources or directly influences PCM improvement is an important area of further study. [Table: see text] No significant financial relationships to disclose.
Predictors of outcome using salvage androgen deprivation therapy after radical prostatectomy.
Authors: Tollefson M. K. , Bergstralh E. J. , Rangel L. J. , Karnes R. J. 
Published: February 2017

74 Background: Nearly all men that experience recurrence of prostate cancer after radical prostatectomy are placed on salvage androgen deprivation therapy (sADT) in an attempt to control the disease. Yet, little is known regarding the efficacy of the treatment, the therapeutic duration or the predictors of treatment failure. Therefore, we examined our experience with sADT after radical prostatectomy in a cohort of patients with no evidence of systemic disease. Methods: We identified 1,373 patients that were treated with sADT after radical prostatectomy prior to the development of systemic disease. Clinical and pathologic variables predicting systemic progression and cancer death were evaluated using the Kaplan-Meier method and compared using the log rank test. Multivariate Cox proportional hazard regression models were used to analyze the impact of these variables on disease progression and survival. Results: Patients were treated with sADT at a median of 4.2 years after surgery. The median PSA at initiation of sADT was 1.6 ng/mL. The majority (1,234, 90%) of patients had a calculable PSA doubling time prior to the initiation of sADT. 275 patients (20.0%) experienced systemic progression at a median of 3.1 years after the start of sADT. 175 patients (12.7%) died of prostate cancer at a median of 4.7 years after the start of sADT. Factors that predicted disease progression after sADT on multivariate analysis included either neoadjuvant or adjuvant ADT (HR - 2.0, p<0.0001), increasing pathologic Gleason Score (HR - 1.18, p=0.009), increasing pathologic stage (HR - 1.3, p<0.0001), PSA at start of sADT (HR - 1.3, p<0.0001) and PSA doubling time (1.65, p<0.0001). Conclusions: Most men treated with sADT after radical prostatectomy prior to the development of systemic progression experience a lengthy disease-free interval. Multivariate predictors of treatment failure include prior adjuvant or neoadjuvant ADT, pathologic Gleason Score, pathologic stage, PSA level at initiation of sADT and PSA doubling time before sADT. No significant financial relationships to disclose.
Quality of life after pelvic radiotherapy with hypofractionated IMRT boost and long-term hormone therapy for locally advanced prostate cancer.
Authors: Quon H. C. , Cheung P. , Loblaw D. A. , Morton G. , Szumacher E. , Danjoux C. , Choo R. , Thomas G. , Kiss A. , Deabreu A. 
Published: February 2017

75 Background: Combined radiotherapy (RT) and long-term hormonal therapy (HT) is a standard treatment option for high-risk prostate cancer. Dose escalated RT alone has been shown to improve disease free survival. Increased sensitivity of prostate cancer to high doses per fraction has led to hypofractionation as a method to radiobiologically escalate dose.We report on the quality of life of patients treated with combined hypofractionated RT and HT. Methods: A prospective phase I/II study enrolling patients with any of: clinical T3, PSA ≥20, or Gleason 8-10. Forty-five Gy (1.8 Gy/fraction) was delivered to the pelvic nodes with a concomitant 22.5 Gy intensity-modulated RT boost to the prostate, for a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions over 5 weeks. Hormonal therapy was administered for 2-3 years. Patient reported outcomes were measured at baseline and every 6 months using the validated Expanded Prostate Cancer Index Composite (EPIC) questionnaire, which measures urinary, bowel, sexual, and hormonal domains. Results: Sixty patients with a minimum 24 months of patient-reported outcomes were analyzed. Mean scores comparing baseline to 24 month values are reported. There were no statistically significant changes in the urinary summary scores (86.3 vs. 86.0, p=0.45) or any of the urinary subscales (function, bother, incontinence, irritative/obstructive). Domain summary score decreases were observed in: bowel by 4.4% (94.7 vs. 90.3, p<0.01), sexual by 27% (44.5 vs. 17.5, p<0.01), and hormonal by 11.9% (93.1 vs. 81.2, p<0.01). Examining time trends in outcomes, most changes occurred within the first 6 months with smaller changes thereafter. Conclusions: Hypofractionated RT combined with long-term HT is associated with good patient-reported urinary and bowel outcomes at 24 months. Sexual and hormonal summary scores are affected, largely due to continued androgen deprivation therapy. Further follow-up is needed to document patient reported outcomes after testosterone recovery. No significant financial relationships to disclose.