bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ten- and 15-year prostate cancer-specific survival in patients with nonmetastatic high-risk prostate cancer randomized to lifelong hormone treatment alone or combined with radiotherapy (SPCG VII).
Authors: Fossa Sophie D. , Widmark Anders , Klepp Olbjorn Harald , Wiklund Fredrik , Angelsen Anders , Damber Jan-Erik 
Published: February 2017

4 Background: After a median observation time of 7.6 years, Scandinavian Prostate Cancer Group VII randomized trial showed a significant 12% reduction of prostate cancer-specific mortality in patients with locally advanced or histologically aggressive prostate cancer who received three months of total androgen blockade followed by radiotherapy and continuous antiandrogen therapy compared to patients with hormonal treatment only (Widmark et al :Lancet [2009]; 373,1174). Here we provide the 10 (15)-year survival results after a median observation time of 10.7 years. Methods: Between February 1996 and December 2002, 875 patients with locally advanced prostate cancer were randomized (Randomization ratio 1:1). Primary endpoint was prostate cancer-specific survival analyzed by intention to treat. This updated analysis is based on death registry data of the Norwegian patients (2/3 of the population), and on data recorded in CRF database available for the Swedish patients. A Swedish death registry analysis is underway, and will be included in the final analysis at the meeting. Results: Prostate cancer death occurred in 118 out of 439 of the antiandrogen treatment group and in 45 out of 436 men in the combination treatment group (p< 0.0001), with death due to any cause in 210 out of 439 and 161 out of 436 men (p=0.0006), respectively. The 10 (15) year cumulative prostate cancer-specific mortality was more than halved after combined treatment: 18.9% (30.7%) and 8.3% (12.4%) (HR=0.35;[p<4.1E-10 for 15 year results]), and overall mortality was 35.3% (56.7%) and 26.4% (43.4%) (HR=0.70; P=0.0006 for 15 year results), respectively. Conclusions: Addition of local radiotherapy to hormonal treatment in patients with non-metastatic locally advanced or high-risk prostate cancer more than halved the 10 and 15 year prostate cancer-specific mortality and substantially decreased overall mortality.
Impact of follow-up imaging on overall and cancer specific survival after radical and partial nephrectomy.
Authors: Strope Seth A. , Sutcliffe Siobhan , Vemana Goutham , Sandhu Gurdarshan Singh , Schootman Mario 
Published: February 2017

401 Background: While imaging after radical and partial nephrectomy has been shown to detect recurrent disease, impacts on mortality are unclear. We assessed effects of imaging on overall-survival (OS) and cancer specific survival (CSS) in Medicare patients. Methods: From linked SEER-Medicare data we defined a cohort of patients treated with radical or partial nephrectomy from 1992 to 2007. All post-operative imaging was collected and stratified as abdominal (CT or US) or chest (CT or CXR). Ascertainment of imaging tests was stopped at the time of possible recurrence based on an algorithm of cancer directed therapy, surgery, or visit to a medical or radiation oncologist. After limiting the cohort to patients treated in hospitals with at least 30 cases, we developed a hospital level average rate of scans per patient for the first five years of patient follow up. The rates were then stratified into three groups for abdominal imaging (Scans less frequent than every 24 months, every 18 to 24 months, more than every 18 months) and chest imaging (Scans less frequent than every 18 months, every 12 to 18 months, more than every 12 months). These categories were then applied in survival analyses at the patient level for OS and CSS and then stratified by final cancer stage. Results: Our cohort included 3,167 patients treated in 62 hospitals. Patients treated in hospitals with higher rates of chest imaging had marginally better OS (HR 0.77 and 0.83, CI 0.60 to 1.01 and 0.63 to 1.08 for scans 12-18 and <12 months respectively), but no effect was found for CSS. Treatment in hospitals with higher rates of abdominal imaging had no impact on OS or CSS. The OS benefit of treatment in hospitals with higher rates of chest imaging appeared limited to patients with stage 1 cancer (HR 0.53 and 0.57, 95% CI 0.38 to 0.76 and 0.40 to 0.80 for scans 12-18 and <12 months respectively). Conclusions: With the exception of chest imaging for stage 1 patients, we found no evidence that higher rates of imaging are associated with better OS or CSS after radical or partial nephrectomy. These results suggest more conservative follow-up imaging protocols can be used in this patient population.
AUA and NCCN surveillance guidelines for RCC: Do they effectively capture recurrences following nephrectomy?
Authors: Stewart Suzanne B. , Lohse Christine M. , Psutka Sarah P. , Cheville John C. , Boorjian Stephen A. , Thompson Robert Houston , Leibovich Bradley C. 
Published: February 2017

402 Background: The American Urological Association (AUA) and the National Comprehensive Cancer Network (NCCN) are highly utilized sources for surveillance strategies following surgical treatment for renal cell carcinoma (RCC). However, the duration of follow-up may be inadequate to capture the majority of recurrences. Herein, we assess the ability of these guidelines to effectively capture recurrences of RCC following primary surgical resection. Methods: We reviewed our institutional database of 3,725 patients treated with radical or partial nephrectomy for M0 sporadic RCC between 1970-2008. For comparison to the AUA guidelines, patients were stratified into low risk following partial nephrectomy (LRp) or radical nephrectomy (LRr) = pT1N0, and moderate/high risk (M/HR) = pT2-4 N0-1. Guideline effectiveness was assessed by calculating the percentage of recurrences detected within the prescribed follow-up periods given for site-specific recurrence: AUA—LRp: 3yrs for all sites; LRr: 1yr for abdominal and 3yrs for chest/bone/other sites; M/HR: 5yrs for all sites; NCCN—6 months for abdominal/chest sites and 5yrs for bone/other sites. Results: Of the 3,725 patients, 2721 (73.1%) underwent radical nephrectomy, 2,210 (59.3%) were classified as pT1 NX-0 and 2,910 (78.1%) as clear cell RCC. Median postoperative follow-up was 8.9yrs (IQR 5.5-14.2) during which 1,114 (29.9%) patients developed recurrence. Of these recurrences, 760 (68.2%) would have been detected using the AUA guidelines and 432 (38.8%) by NCCN recommendations. Within AUA risk groups, 37.2% recurrences were captured in LRp, 31.4% in LRr and 80.2% in M/HR. Capture of 90% of recurrences in the abdomen and chest would require surveillance for 9yrs and 8 yrs, respectively in LRp, 15yrs and 12yrs in LRr and 11yrs and 10yrs in M/HR. Conclusions: Duration of follow-up recommended by current surveillance algorithms by the AUA and NCCN do not adequately capture many recurrences in RCC following radical or partial nephrectomy. Guidelines using risk stratification and site-specific recurrence parameters to assign length of surveillance may allow providers to better individualize surveillance regimens.
Understanding treatment disconnect and mortality trends in renal cell carcinoma using tumor registry data.
Authors: Smaldone Marc C. , Egleston Brian , Hollingsworth John M. , Hollenbeck Brent K. , Miller David Christopher , Kim Simon , Handorf Elizabeth , Wong Yu-Ning , Uzzo Robert G. , Kutikov Alexander 
Published: February 2017

403 Background: Previous research has demonstrated a rise in overall and cancer specific mortality over time despite increased detection and treatment of kidney cancer, termed “treatment disconnect.” Our aim was to assess the impact of missing data and rising incidence on mortality trends using national tumor registry data. Methods: Using Surveillance, Epidemiology, and End Results (SEER) data, we identified all patients with a kidney cancer diagnosis from 1973-2009. We estimated overall mortality rates by tumor size after accounting for lags from diagnosis to death and using multiple imputation for missing data. Mortality rates for all patients irrespective of tumor size were also estimated after adjustment for prior cumulative incidence using ridge regression. Results: 73,647 patients met inclusion criteria, of which 22.7% had missing tumor size data. Compared to observed rates, significant decreases in the change in mortality rate per 100,000 US population from 1983 to 2009 were noted for 2-4cm (Δobs1.58 versus Δimp1.34; p=0.003), 4-7cm (Δobs1.61 versus Δimp0.79; p<0.001), and >7cm (Δobs1.55 versus Δimp0.19; p<0.001) tumors following missing data imputation, while no differences in change of rate were noted for tumors <2cm (Δobs0.29 versus Δimp0.25). In a separate analysis, holding the incidence of kidney cancer constant over time, the temporal increase in overall mortality for all patients was attenuated (p<0.001 for test of difference in slope) when comparing observed (3.9 to 6.8) and estimated (5.9 to 7.1) rates, suggesting that rapidly rising incidence may also influence reported mortality trends. Conclusions: Missing data and rising incidence rates may contribute substantially to the “treatment disconnect” phenomenon when examining mortality rates in kidney cancer using tumor registry data.
The effect of sunitinib on biomarkers and tumor heterogeneity in metastatic clear cell renal cancer.
Authors: Stewart Grant , Laird Alexander , O'Mahony Fiach , Eory Lel , Lubbock Alexander , Nanda Jyoti , O'Donnell Marie , Mackay Alan , Mullen Peter , McNeill Alan , Riddick Antony , Aitchison Michael , Berney Daniel , Bex Axel , Overton Ian , Harrison David James , Powles Tom 
Published: February 2017

408 Background: The purpose of this work was to investigate the effect of sunitinib on tumour biomarkers and assess intratumoural heterogeneity in metastatic clear cell renal cancer (mRCC). Primary tumours and metastatic sites were examined. Methods: Multiple fresh frozen tissue samples (median=4) were taken from sunitinib naive (n=23) and sunitinib treated (18 weeks at sunitinib 50mg) patients (n=27) with mRCC. Tissue was taken from the primary renal tumours. Multiple analysis of DNA (aCGH), mRNA (Illumina Beadarray) and protein lysates (reverse phase protein array) were performed on each tumour sample. Analysis of metastatic tissue occurred where possible (n=4). A cohort of matched untreated and sunitinib/pazopanib treated paraffin embedded mRCC samples from 3 clinical trials was used for validation with automated quantitative analysis. Results: Treated and untreated patient had similar patient characteristics. Significant intratumoural heterogeneity in DNA, RNA and protein occurred. Sunitinib was associated with increased intratumoural heterogeneity in protein expression (p<0.05), but not DNA or RNA. Despite this heterogeneity, significant changes to protein expression with sunitinib occurred. Four proteins changed significantly in terms of both expression and variance with sunitinib (BCL2, MLH1, CAIX and mTOR; p<0.05 for each). Elevation of CAIX expression in sunitinib treated patients was confirmed in the validation cohort (p=0.01). Low levels of CAIX correlated with poor outcome in treated samples (HR=0.26, 95% CI: 0.11-0.61, p=0.001). A positive correlation between protein expression in the primary tumour and metastatic sites occurred. Individual metastasis within patients exhibited a variable radiological response to therapy, which was equally marked in the genetically more homogeneous primary tumours. Conclusions: Intratumoural heterogeneity occurs on many levels in mRCC. Sunitinib is associated with increase in protein heterogeneity. Despite this, upregulation of CAIX is a potential prognostic biomarker.
Correlation between patient-reported fatigue and hemoglobin (Hgb) levels in metastatic renal cell carcinoma (mRCC) patients (pts) receiving sunitinib (SU).
Authors: Davis Mellar P. , Matczak Ewa M. , Chen Connie , Korytowsky Beata , Bhattacharyya Helen , Lin Xun , Rini Brian I. 
Published: February 2017

418 Background: Low Hgb is linked with fatigue in cancer pts; however, the onset and severity of fatigue is multifactorial. The approved SU dosing schedule in mRCC is 4 weeks on treatment, 2 weeks off, and quality of life (QoL) when examined on day 28 is significantly worse than on day 1 of each cycle. The relationship between pt-reported fatigue and Hgb levels with SU in mRCC was investigated. Methods: Two randomized clinical trials of SU were combined to examine the pt-reported fatigue item from FKSI-15 which asks pts to indicate their level of fatigue on a 5-point Likert scale from 0=“not at all” to 4=“very much”. Data were collected at baseline (BL; cycle 1, day 1) and on days 28 and 42 of each 42-day cycle. For each visit, only pts who had data for both fatigue and Hgb at BL were included in the analysis. Results: 481 pts were included. Fatigue and Hgb levels at BL and over cycles 1–6 are shown in the table. Pts reported worse fatigue (higher score) at day 28 of each cycle than on day 42. Fatigue scores typically ranged from 1= “a little bit” to 2=“somewhat”. Changes in Hgb levels, however, were modest and opposite to fatigue changes i.e. were higher on day 28 of each cycle and lower on day 42. Findings were similar beyond cycle 6. Conclusions: Pts indicated less fatigue on day 42, after the 2-week break, than on day 28 of each cycle, consistent with previous overall QoL findings. Low Hgb is not associated with worse fatigue in mRCC pts receiving SU.This may be due to the multifactorial nature of fatigue. The ‘on’ and ‘off’ periods in intermittent dosing are important considerations of patients’ full experience of QoL. [Table: see text]
Utility of 2-(18F) fluoro-2 deoxy-D-glucose PET/CT in advanced papillary renal cell carcinoma.
Authors: Shuch Brian , Stamatakis Lambros , Chen Clara , Gautam Rabindra , Merino Maria , Choyke Peter L. , Linehan W. Marston , Srinivasan Ramaprasad 
Published: February 2017

419 Background: 2-(18F) fluoro-2 deoxy-D-glucose (FDG) PET/CT is used infrequently in renal cell carcinoma (RCC) based on modest sensitivity in patients with clear cell kidney cancer. We evaluated the ability of FDG PET/CT to identify metastatic kidney cancer in patients with the second most common variant, papillary RCC. Materials and Methods: Patients with papillary RCC who underwent FDG PET/CT in conjunction with anatomic imaging were identified in a review of our clinical database. The ability of FDG PET/CT to detect malignant lesions (categorized by radiographic criteria) was evaluated. Results: Imaging studies from 42 patients with metastatic papillary RCC were reviewed. A total of 215 lesions were characterized as metastatic based on radiologic features. The median lesion size and lesions per patient were 2.0 cm and 5, respectively. Of these, 200 lesions were correctly classified as malignant by PET/CT (sensitivity, 93.0%, 95% confidence interval (CI) 88.8-95.7%). Of histologically confirmed lesions, 35 of 39 were PET positive (sensitivity, 89.7%, CI-76.4-95.9%). FDG PET/CT sensitivity did not appear to differ by lesion size, site, or papillary subtype. In a patient based analysis, all 42 patients had evidence of at least one FDG PET/CT avid lesion (sensitivity 100%, (95% CI 91.6-100%). Conclusions: FDG PET/CT is a highly sensitive modality for identifying extra-renal disease associated with papillary RCC. These data suggest that FDG PET/CT might be a clinically useful modality in the staging and surveillance of this patient population.
Active surveillance as a treatment option for metastatic or recurrent renal cell carcinoma.
Authors: Park Inkeun , Lee Jae-Lyun , Ahn Jin-Hee , Jeong In Gab , Song Cheryn , Hong Bum-Sik , Hong Jun Hyuk , Kim Choung-Soo , Ahn Hanjong 
Published: February 2017

426 Background: Metastatic renal cell carcinoma (MRCC) often presents with very indolent course without any symptom, and treatment (Tx) for MRCC is mostly palliative rather than curative in a molecular target agents era. There exist several Tx options for MRCC, but all available agents have considerable toxicities, cause economic burden to patients (pts), and impair quality of life. We retrospectively evaluate outcomes of active surveillance for asymptomatic MRCC pts. Methods: We enrolled MRCC pts who was followed-up with deferred treatment in our institution between 2000 and 2012. Clinical characteristics, response to active surveillance, predictive factor for time-to-progression (TTP), and response to succeeding first line VEGFR TKIs were analyzed. Results: Of 58 pts, 42 had recurrent disease and 14 had initially metastatic disease. Most pts had good Karnofsty PS (KPS), 100% for 39 pts and 90% for 14 pts. Lung (47 pts) and lymph nodes (18 pts) were most common site of metastasis. During active surveillance, 83% of patients had stable disease (SD) as their best response. Only 17% of patients had progressive disease (PD) as their initial response. Ultimately, 47 pts had PD finally until data cut-off date. With a median F/U period of 31.4 months, 47 patients experienced disease progression with a median TTP of 12.4 months (95% CI, 8.4~16.5). A median OS was 91.1 months (95% CI, 30.7-151.6). Multivariate analysis revealed that KPS < 100, presence of liver metastasis, time from diagnosis to active surveillance less than 1year, and neutrophilia were independent predictive factors for worse TTP. After PD, 30 pts proceeded to systemic treatment (14 sunitinib, 11 pazopanib, 4 immunotherapy, and 1 temsirolimus). Objective response rate were 71% for sunitinib, and 46% for pazopanib. Conclusions: This study suggests that active surveillance without any intervention could be a viable treatment option for the first-line approach in asymptomatic MRCC pts, especially for those who have good performance status without neurtrphilia or liver metastases. The possibility of disease stabilization should be considered before initiation of any active treatment and when assessing the activity of any treatment in terms of time to progression.
Phase II clinical trial of bevacizumab plus ixabepilone in renal cell carcinoma.
Authors: Burotto Pichun Mauricio Emmanuel , Acquavella Nicolas , Edgerly Maureen , Bates Susan Elaine , Balasubramaniam Sanjeeve , Fojo Antonio Tito 
Published: February 2017

427 Background: Metastatic renal cell carcinoma (mRCC) remains incurable. Seven targeted agents are approved for mRCC, five targeting VEGFR and two m-TOR inhibitors. Most approvals have been based on improvements in progression free survival (PFS). Preclinical data indicates synergism of ixabepilone and bevacizumab. Methods: Patients with histologically confirmed mRCC with at least one previous therapy received ixabepilone [6mg/m2/d X 5d] plus bevacizumab [15 mg/kg] every 21 days. The primary endpoint was PFS by RECIST. Secondary endpoints were response rate, overall survival, and safety. In addition to “conventional” efficacy assessments, we calculated the growth rate constant as a measure of efficacy. Results: Thirteen patients have been enrolled. The median number of prior therapies was two (range 1-5). Nine (69%) have stable disease as best response with two (15%) partial responses. Median time to progression (TTP) was 6.39 months. The growth rate constant (g) was 0.0021/day and the regression rate constant (d) was 0.0032/day. Six patients discontinued treatment due to progression; one patient died. Principal toxicities including hypertension, fatigue, anemia and thrombocytopenia led two patients to discontinue therapy. One continues on study after 25 cycles. Accrual continues. Conclusions: Ixabepilone plus bevacizumab has activity in mRCC. A median TTP of 6.39 months compares favorably with 3.9-4.8 months for approved second line therapies. The calculated growth rate of 0.0021/day in this refractory population is indistinguishable from a value of 0.0022/day with single agent bevacizumab in treatment-naive mRCC. However, we cannot discern if this reflects bevacizumab activity even in refractory disease or a beneficial ixabepilone effect. Clinical trial information: NCT00923130.
Does nonsurgical management for localized kidney cancer equate to active surveillance in the SEER-Medicare population?
Authors: Smaldone Marc C. , Egleston Brian , Kim Simon , Handorf Elizabeth , Geynisman Daniel M. , Wong Yu-Ning , Uzzo Robert G. , Kutikov Alexander 
Published: February 2017

444 Background: Differentiating between patients with small renal tumors not selected for treatment from those who choose elective active surveillance (AS) using administrative data is a significant challenge. Using active treatment as a benchmark, our objective was to compare survival outcomes between all patients with localized kidney cancer who received non-surgical management (NSM) with those meeting more stringent NSM criteria who are more likely to clinically resemble AS. Methods: Using linked SEER-Medicare data, we identified all patients ≥66 years old with localized T1 (<7cm) Renal Cell Carcinoma from 1995-2009. Treatment groups were defined as active treatment (partial or radical nephrectomy), all NSM (no treatment within 6 months of diagnosis), and stringent NSM (further exclusion of patients with lack of imaging or presence of hospice claims). Patients undergoing ablative treatment were excluded from analyses. Overall and cancer specific mortality were assessed using Cox and Fine and Gray proportional hazard models with propensity score based weighting. Results: Of 15,450 identified patients, 2,089 (13.5%) underwent NSM. Of these, 1,182 (56.6% of NSM, 7.7% of overall sample) met stringent NSM criteria. Following adjustment, the all NSM group demonstrated significant increases in cancer specific (sHR 1.91 [CI 1.26-2.88]) and overall (HR 1.49 [CI 1.16-1.92]) mortality compared to patients undergoing active treatment. In contrast, for patients meeting stringent NSM criteria, these differences in cancer specific (sHR 1.48 [CI 0.82-2.68]) and overall (HR 1.33 [CI 0.998-1.77]) mortality were attenuated and no longer met statistical significance. Conclusions: Compared to active treatment, patients meeting stringent NSM criteria demonstrated improved survival outcomes when compared to all-comers with localized kidney cancer who were managed non-surgically. Our findings support that a validated, claims-based algorithm that more accurately identifies patients undergoing elective AS is needed to objectively assess the safety and effectiveness of this clinical strategy.