bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of active surveillance prior to systemic target therapy in patients with metastatic renal cell carcinoma.
Authors: Matsubara Nobuaki , Mukai Hirofumi , Naito Yoichi , Itoh Kuniaki 
Published: February 2017

444 Background: The clinical course of metastatic renal cell carcinoma (mRCC) has a wide spectrum that ranges from indolent to rapidly progressive disease. Initial active surveillance (AS) followed by deferred systemic target therapy might be a treatment option in a subpopulation of patients with indolent mRCC. However, very few studies have been published about AS and its outcome as well as potential predictive factor that might be associated with indolent mRCC. Here, we report clinical outcomes of mRCC patients who initially were monitored by AS. Methods: We retrospectively reviewed and analyzed the clinical and pathological data of mRCC patients who initially were monitored by planned AS prior to systemic therapy due to asymptomatic or slowly progressive disease at National Cancer Center Hospital East between 2000 and 2011. The primary outcome measures were progression-free survival (PFS) and overall survival (OS). Results: A total of 29 patients were eligible for this analysis. The median age at diagnosis was 69 years, and all patients had a good general condition with a performance status of 0 or 1. A total of 65% of patients had recurrent disease and 35% were in stage 4. All of the patients had undergone nephrectomy, and 86% had clear cell carcinoma. None of the patients was categorized into a poor risk group according to both MSKCC and Heng criteria. The median follow-up period was 35.4 months. During the follow-up period, disease progression was observed in 72% of patients but only 14% died. The median PFS time was 26.1 months. After disease progression was observed, only 58% of these patients received treatment or intervention. The median OS have not been reached yet, but 12, 24 and 48 months OS rates were 96.4, 88.7 and 83.8%, respectively. Conclusions: PFS and OS of patients who underwent AS were extremely favorable. For these indolent subpopulations, AS might be a treatment option, so toxic and expensive systemic target therapy could be deferred for a significant period of time without prognostic disadvantage. However, further observational study with a larger sample size might be needed in order to identify the exact subpopulation eligible for AS.
Association of renal cell carcinoma and hematologic malignancy.
Authors: Varella Leticia , Chintapatla Rangaswamy , Wiernik Peter H. , Rusciano Valerie , Dutcher Janice P. 
Published: February 2017

449 Background: An increased incidence of both RCC and HM occurring in the same patients has been reported. Also, a relationship between adenocarcinoma and HM has been previously suggested. Moreover, detailed family history in our patients with RCC suggested an increased incidence of HM in their family members. The purpose of this study is to characterize the HM in relatives of patients with RCC. Methods: Data from 700 patients with RCC seen by us from 2004 to the present were retrospectively evaluated through chart review. The patient, family history and pathology characteristics were collected to determine the frequency of HM in first and second-degree relatives of patients with RCC. Pedigrees were then constructed and subtypes of HM were characterized. Results: A family history of HM was observed in 74 relatives involving 59 families. Of these, 50/74 cases of HM were in first-degree relatives and 19/74 were in second-degree relatives. The most common HMs were lymphoma and leukemia: 24 non-Hodgkin’s lymphoma, 8 Hodgkin’s lymphoma, 8 lymphoma not further specified (NOS), 11 chronic lymphocytic leukemia, 1 chronic myeloid leukemia, 1 acute myeloid leukemia, 5 acute leukemia NOS and 4 leukemia NOS. Other HM observed were multiple myeloma in 2 patients, Waldenström’s macroglobulinemia, myelodysplastic syndrome, and myelofibrosis. Additionally, 2 relatives had blood cancers that were NOS. Of the 59 patients with RCC, 40 had clear cell histology, 4 papillary, 3 chromophobe, 1 sarcomatoid, 1 transitional and in 10, RCC histology was not recorded. Conclusions: HM is observed in patients with RCC with increased frequency compared with the SEER database. We now observed an increased frequency of HM in relatives of patients with RCC. The majority of HMs observed were B-cell malignancies, as we previously reported for HMs that occur in patients with breast cancer or RCC. The etiology of this association remains unclear, but suggests a common etiopathogenesis for RCC and B-cell tumors. Genetic mutations, hereditary immunological defects, and environmental factors may be involved. A larger study with statistical evaluation for confirmation is required. We plan to collect serum and tissue samples from patients and relatives for future molecular studies.
High-dose bolus interleukin-2: Correlating response rate with number of doses received.
Authors: Patel Jolly , Fishman Mayer N. , Goetz Dawn 
Published: February 2017

452 Background: Administration of high-dose interleukin-2 (IL-2) in metastatic renal cell carcinoma (MRCC) has higher response and survival rates when compared to low dose or subcutaneous administration. In patients who achieve a response, it may be at the expense of more toxicity risk, from more doses. The association of the major response rate with the number of high dose boluses or cumulative dose received is of interest. The primary objective of this study is to evaluate a direct correlation with response and cumulative dose or the total number of doses received. Methods: A retrospective chart review was conducted of all patients at H. Lee Moffitt Cancer Center diagnosed with metastatic renal cell carcinoma who received high dose bolus IL-2 from September 30th, 1999 to September 30th, 2010. The cumulative dose and the number of doses of IL-2 received was recorded and associated with categorical complete response [CR], partial response [PR], stable disease [SD] or progressive disease [PD] response, by treating physician assessment. Sites of metastasis were also documented. The incidence of adverse effects such as renal failure, transaminitis, cardiac arrhythmias, thrombocytopenia as well as rates of infection and ICU transfers were tabulated. Results: 31 out of 55 patients analyzed were assessed at least with stable disease in response to IL-2. Six achieved a CR, 11 achieved a PR, 14 had stable disease and 24 patients had PD as best responses. Among those with CR or PR to IL-2, they received approximately 30 doses of IL-2 (p=0.027 vs. those not in that category). Converesely, those who received a higher cumulative dose were also more likely to respond (p=0.0077). With respect to adverse events, 58% of patients experienced acute renal insufficiency, 63% transaminitis, 40% arrhythmias, and 45% thrombocytopenia. 55% required dopamine use at any point and 11% required use of additional pressors; 15% required an ICU transfer at some point, and approximately 4% developed a documented infection. Conclusions: Cumulative dose or number of high dose bolus doses received is associated with a statistically significant difference in response rate, within the limitations of this retrospective analysis.
Efficacy of sorafenib in advanced renal cell carcinoma (RCC) independent of prior treatment, histology, or prognostic group.
Authors: Tafreshi Alireza , Thientosapol Eddy , Liew Mun Sem , Guo Yuan , Quaggiotto Melissa , Boyer Michael J. , Davis Ian D. 
Published: February 2017

465^ Background: Multiple targeted therapies have become available for RCC over the past decade. Sorafenib is an orally active multikinase inhibitor which has been shown to improve progression free survival in low-risk and intermediate-risk status advanced clear-cell RCC after previous systemic therapy. Methods: Between May 2006 and December 2010, patients with advanced RCC with either clear cell or non-clear cell histopathology who had progressed on prior systemic chemotherapy or were treatment naïve, ECOG performance status 0-2, commenced treatment with sorafenib (400-mg twice daily continuously) through an expanded access clinical trial in two tertiary centres in Sydney and Melbourne. We report the pooled outcomes of these two studies. Results: Total 47 patients with metastatic RCC were treated with sorafenib. The median overall survival of advanced RCC was 11.9 months. After median follow up of 51.3 months, the median PFS was 6.5 months. 38 patients died by the time of analysis. Overall 1 patient showed complete response (CR), 6 patients (13%) had partial response (PR), and 29 patients (62%) had stable disease (SD) as the best response. 8 (17%) had non-clear cell histopathology and 5 (10%) had sarcomatoid features. In non-clear cell cohort, 5 patients (62.5%) showed SD. 23 (49%) patients were treatment naïve; 1/23 showed CR, 5/23 had PR and 13/23 had SD (clinical benefit: 83%). Overall 14 (30%) and 22 (47%) patients had high risk status according to MSKCC and Heng prognostic scores, respectively. Median PFS for poor prognostic patients was 5.1 and 4.2 months based on MSKCC and Heng scores, respectively. In MSKCC poor prognostic group, 1 patient had CR, 2/14 showed PR and 8/14 had SD (clinical benefit: 79%). In Heng poor prognostic group, one patient had CR, 2/22 showed PR and 13/22 had SD (clinical benefit: 73%). Sorafenib-related serious adverse events were seen in 10 patients. The most common adverse events were hand-foot syndrome (53%), rash (47%), fatigue (42%), nausea (40%), and diarrhoea (32%). Conclusions: This study confirms the efficacy and tolerability of sorafenib in a different spectrum of advanced RCC patients including non-clear cell histology, poor prognostic status and as first-line treatment. Clinical trial information: ACTRN12606000140550.
Identification of biomarkers for overall survival of patients with metastatic renal cell carcinoma treated with MGN1601.
Authors: Grünwald Viktor , Weikert Steffen , Schmidt-Wolf Ingo G.H. , Hauser Stefan , Weith Ekaterina , Schroff Matthias , Schmidt Manuel , Tschaika Marina , Wittig Burghardt 
Published: February 2017

468 Background: The cell-based therapeutic cancer vaccine MGN1601 consists of two active pharmaceutical ingredients in fixed combination. Fourfold gene-modified, allogeneic tumor cells expressing IL-7, GM-CSF, CD80, and CD154 through MIDGE gene expression vectors are combined with the DNA-based immunomodulator dSLIMas a TLR-9 agonist. In the phase I-II clinical trial (ASET trial) heavily pre-treated patients with metastatic renal cell carcinoma (mRCC) were enrolled. Methods: TheASET study has been conducted as a multicenter, open, single-arm phase I-II study. The treatment phase (TP) consisted of 8 intradermal vaccinations, administered within 12 weeks. We analysed known mRCC prognostic factors for their predictive value, i.e. safety laboratory and immunological parameters, quality of life, local reactions and other patients’ characteristics. Results: 19 patients from the ASET study, who received at least one vaccination (ITT population), were included in the biomarker evaluation. The median overall survival (mOS) in the ITT population is currently 25 weeks. mOS of patients who discontinued TP prematurely was only 10 weeks. However, mOS of those patients who completed at least TP is not yet mature for statistical calculation (NR), but is currently estimated as 69 weeks, resulting in a highly significant difference (10 weeks vs. NR, p < 0.001). Patients with an absolute lymphocyte counts (ALC) at baseline of ≥1,000/μL had increased overall survival (mOS NR vs. 16 weeks, p = 0.013), if compared to those with an ALC <1,000/μL. Neutrophil lymphocyte ratios (NLR) at baseline of >3, bone and liver metastasis, high MSKCC score were identified as risk factors associated with lower overall survival. ALC ≥1,000/μL after three MGN1601 vaccinations (week 5) was even more significantly associated with increased overall survival (mOS NR vs. 17 weeks, p = 0.007). The NLR and quality of life improvement at week 5 as well as local reactions at injection sites seem to correlate with OS. Conclusions: MGN1601 shows promising efficacy in late stage mRCC patients. The identified parameters should be further investigated as potential biomarkers for efficacy. Clinical trial information: NCT01265368.
Defining heminephrectomy for cancer.
Authors: Klink Joseph C. , Khalifeh Ali , Samarasekera Dinesh , Panumatrassamee Kamol , Kaouk Jihad 
Published: February 2017

473 Background: The word heminephrectomy originally referred to the removal of half of a kidney with a duplicated collecting system. In the era of partial nephrectomies, heminephrectomy is sometimes used to describe the removal for tumor of >30% of the parenchyma of a non-duplicated kidney. We herein propose a new definition of heminephrectomy: excision of the upper or lower pole of the kidney, removing at least 30% of the parenchymal mass, cutting to hilar fat, and transecting the collecting system. Methods: Our institutional database of robotic and laparoscopic partial nephrectomies was queried for patients who underwent a partial nephrectomy for tumor between 2002 and 2011. Patients who had a heminephrectomy for obstruction in a duplicated collecting system were excluded. The patients who had a heminephrectomy by our strict definition were compared to the remainder of patients who had a partial nephrectomy. Logistic regression was used to compare outcomes between the two groups. Results: 61 patients met our strict definition of heminephrectomy out of 643 patients who underwent a partial nephrectomy for tumor. Heminephrectomy and non-heminephrectomy patients were similar in age, gender, BMI, ASA score, proportion of left- versus right-sided tumors, solitary kidney status, preoperative creatinine and GFR. (all p>0.1). The tumors in the heminephrectomy group were larger (5.1 vs. 2.8 cm, p<0.001) and had a higher R.E.N.A.L nephrometry score (8.5 vs. 6.5, p<0.001). Operative outcomes reflected the high complexity of performing a heminephrectomy. Estimated blood loss was greater (373 vs. 267 ml, p=0.04), operative time was longer (214 vs. 185 minutes, p<0.001), warm ischemia time was longer (25 vs. 20 minutes, p=0.002), and the rate of intra-operative complications was greater (11% vs. 4%, p=0.02) in the heminephrectomy group. On multivariable analysis adjusted for age, preoperative GFR, R.E.N.A.L. score, and warm ischemia time, heminephrectomy was a significant predictor of lower post-operative GFR (p<0.001). Conclusions: Our strict definition of heminephrectomy performed for tumor in a non-duplicated system will allow precise clinical and research communication about heminephrectomy patients and may aid in the prediction of outcomes after partial nephrectomy.
Elevated pS6K levels in the sarcomatoid component of tumors derived from patients with metastatic renal cell carcinoma (mRCC).
Authors: Pal Sumanta Kumar , Tong Tommy , He Miaoling , Wu Huiqing , Liu Xueli , Carmichael Courtney , Lau Clayton , Nelson Rebecca A. , Figlin Robert A. , Jones Jeremy 
Published: February 2017

475 Background: Consistent with other retrospective analyses, data from our institutional experience indicates that patients (pts) with sarcomatoid mRCC have a poorer outcome as compared to pts that lack sarcomatoid features (Pal SK, et al. Urol Oncol 2012). The preponderance of correlative studies to date focused on epithelial-to-mesenchymal transition (EMT) as a driver of sarcomatoid disease; however, the role of vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) signaling is poorly understood. Methods: Of 270 pts with mRCC in our institutional database, 21 pts were noted to have sarcomatoid features. Thirteen of these pts had available tissue from nephrectomy or diagnostic biopsy. An additional 13 pts with mRCC and available tissue were identified from the database who had a similar MSKCC risk stratification but lacked sarcomatoid features. Immunohistochemical staining were performed for moieties related to VEGF-mediated signaling (pS6K) and EMT (Twist, E-cadherin and N-cadherin). Results: Among matched pts with and without sarcomatoid features (n=13 for each group), 9 pts (69.2%) in each group had poor risk disease by MSKCC criteria, while the remainder had intermediate risk disease. Given our risk-matching approach, median survival was similar in both groups (6 mos in pts with no sarcomatoid features vs. 9 mos in pts with sarcomatoid features, p = NS). In evaluable specimens from pts with no sarcomatoid features, the proportion of cell staining positively for pS6K was 24.4%. A higher proportion of pS6K staining was found in pts with sarcomatoid mRCC, both in sarcomatoid components (60.0%) and non-sarcomatoid components (52.5%). Staining for N-cadherin, E-cadherin, and Twist were highly variable, and no observable differences between groups were identified. Conclusions: Although chemotherapeutic strategies are a common 1st-line approach to sarcomatoid mRCC, the finding of higher pS6K staining in this population suggest the potential for currently approved targeted therapies in this disease. Prospective assessment of VEGF- and mTOR-directed therapies for sarcomatoid mRCC, as in ECOG 1808 (NCT01164228), should be encouraged.
Updated interim analysis (IA) of COU-AA-302, a randomized phase III study of abiraterone acetate (AA) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) without prior chemotherapy.
Authors: Rathkopf Dana E. , Smith Matthew Raymond , De Bono Johann Sebastian , Logothetis Christopher , Shore Neal D. , De Souza Paul L. , Fizazi Karim , Mulders Peter , Mainwaring Paul N. , Hainsworth John D. , Beer Tomasz M. , North Scott A. , Fradet Yves , Griffin Thomas W. , Park Youn Choi , Kheoh Thian San , Small Eric Jay , Scher Howard I. , Molina Arturo , Ryan Charles J. 
Published: February 2017

5 Background: AA, a specific inhibitor of CYP17, blocks androgen biosynthesis and improves overall survival (OS) in mCRPC post-docetaxel (Lancet Oncol 2012;13:983-92). This pre-specified updated IA (55% total OS events) extends previous IA for COU-AA-302 evaluating clinical benefit of AA vs prednisone (P) in mildly symptomatic or asymptomatic pts with progressive mCRPC without prior chemotherapy. Methods: 1088 pts were stratified by Eastern Cooperative Oncology Group performance status (ECOG-PS, 0 vs 1) and randomized 1:1 to AA 1000 mg + P 5 mg po BID vs Placebo + P. Co-primary endpoints: radiographic progression-free survival (rPFS) and OS. Median time with 95% CI was estimated using the Kaplan-Meier method. The O’Brien-Fleming Lan-DeMets α-spending function was used for OS. Results: At 55% IA, OS, rPFS and secondary endpoints all favored the AA arm (Table). Median follow-up = 27.1 mos. A post hoc sensitivity multivariate analysis for OS using known prognostic factors supported primary results (HR 0.74, P = 0.0017). Grade 3/4 AEs (AA, P) (%): hypertension 4.2 vs 3.1; hypokalemia 2.6 vs 1.9; ALT↑ 5.5 vs 0.7; AST↑ 3.1 vs 0.9. Conclusions: In updated IA of COU-AA-302, improvement in rPFS (risk reduction 47%) remained statistically significant. Risk of death decreased by 21% but did not reach pre-specified efficacy boundary. Median OS for AA (35.3 mos) is the longest reported for this mCRPC population. Secondary endpoints were clinically and statistically significant; safety profile despite longer exposure remains favorable. Targeting extragonadal androgen synthesis reduces morbidity associated with disease progression in mCRPC pts without prior chemotherapy. Clinical trial information: NCT00887198. [Table: see text]
Evaluation of the UCSF cancer of the prostate risk assessment for prediction of biochemical recurrence (CAPRA) to predict which patients need dose escalation in intermediate-risk disease.
Authors: Taussky Daniel , Krishnan Vimal , Bahary Jean-Paul , Nguyen-Huynh Thu-Van 
Published: February 2017

54 Background: The University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a validated preoperative index which predicts recurrence free survival and the risk of adverse pathological features after prostatectomy. We analyzed the value of the CAPRA score to predict which patients might benefit from dose escalation in a randomized dose-escalation trial for intermediate risk patients. Methods: We analyzed 119 patients with intermediate risk prostate cancer (Gleason ≤ 6 and PSA 10-20 or Gleason 7 and PSA <10). Patients were randomized between external beam radiotherapy (EBRT) doses of either 70.2 Gy or 79.2 Gy (1.8 Gy per day). All patients had a follow up of at least 2 years. Biochemical failure (BF) was defined with the Phoenix definition. Difference between CAPRA groups was calculated using Kaplan-Meier method. Results: Twenty percent (24/119) had BF. Median time to BF was 60.5 months (1-102) and median follow up for patients without failure was 66 months (25-102). A CAPRA score of 0-2 (risk of recurrence 5y post prostatectomy <10%) was present in 16%, a score of 3-5 (5y risk 18-26%) in 72% and CAPRA 6 (5y risk 37%) in 12%. Stratified according to the 3 CAPRA groups 0%, 20% and 50% ofpatients had a recurrence. The difference between the 3 groups was significant (p=0.019). When stratified according to treatment arm, differences remained significant (p=0.025). None of the patients with a CAPRA 0-2 had biochemical recurrence, even with 70.2 Gy only. When analyzing only patients with a CAPRA score of 3-5, patients in the treatment arm with 79.2 Gy, had less BF with 15% compared to 26% in the arm with 70.2 Gy (p=0.187). The 2 survival curves start to split at 5y of follow-up. Conclusions: The CAPRA score seems to be a promising, clinically easily applicable tool to predict for patients who might benefit from dose escalation. Patients with a CAPRA score of 0-2 do not seem to benefit from dose escalation, but there is a trend for a benefit in patients with a CAPRA 3-5. Clinical trial information: NCT00033631.
Association of radical prostate cancer therapy with a survival benefit in the older man.
Authors: Cathcart Paul , Johal Amundeep , van der Meulen Jan , Emberton Mark 
Published: February 2017

66 Background: Data from several recent randomised controlled trials have suggested that older men have little to gain from radical prostate cancer therapy. In contrast, observational studies have suggested that older men might be at increased risk of prostate cancer related death than their younger counterparts. Using a national cancer registry, we sought to explore this issue further. Methods: English national mortality records for an 11 year period between 1997 and 2008 were linked to national hospital admission records together with national cancer registration records to generate a working dataset. Complete data were available on 75,735 men. Competing risks regression analysis was employed to identify the effect of age on Prostate Cancer Specific mortality. Results: Older men were more likely to have high-grade prostate cancer (<70 yrs: 20% v’s >79 yrs: 36%) and be staged with locally advanced (<70 yrs: 20% v’s >79 yrs: 35%) or metastatic disease (<70 yrs: 18% v’s >79 yrs: 25%). Older men were less likely to receive radical therapy (<70 yrs: 46% v’s >79 yrs: 4%) although they were more likely to die of their disease. 8-year overall mortality for low, intermediate and high risk disease in men <70 was 8%, 11% and 31% compared to 34%, 36% and 54% for men >79. Comparable figures for 8-year prostate cancer specific mortality were 1%, 5% and 22% for men <70 and 8%, 10% and 32% for men >79.The Number Needed to Treat (NNT) to save one prostate cancer related death for men with low risk disease aged less than 70 was 100 compared to 20 and only 6 for men aged <70 with intermediate and high risk disease respectively. For men aged between 75 and 79, radical prostate cancer therapy was only associated with a survival benefit in men with high risk disease (OR: 0.49, 95% CI 0.36-0.66, p<0.001) for which the NNT was 5. Conclusions: Older men present with more advanced and more aggressive prostate cancer and as such are more likely to die from their disease. Radical therapy was associated with a survival benefit up to the age of 80 providing therapy was targeted to those with higher risk disease.