bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acquired hypothyroidism as a predictive marker of outcome in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine-kinase inhibitors (TKIs): A literature-based meta-analysis.
Authors: Nearchou Andreas Demetrios , Valachis Antonis , Lind Pehr , Akre Olof , Sandstrom Per 
Published: February 2017

500 Background: The development of hypothyroidism in patients with mRCC during treatment with the tyrosine kinase inhibitors (TKIs) sunitinib and sorafenib is a well-established side effect. The potential role of hypothyroidism as predictive marker of outcome has been studied with conflicting results. The aim of the present meta-analysis was to assess the predictive value of hypothyroidism for both progression free (PFS) and overall survival (OS) in patients with mRCC treated with TKI. Methods: We searched PubMed as well as the electronic abstract databases of the major international congresses’ proceedings to identify all eligible studies which reported a correlation of the development of hypothyroidism during treatment with TKI and outcome in patients with mRCC. Hazard ratios (HRs) with 95% confidence intervals (CIs) for PFS and OS were obtained from these publications and pooled in a meta-analysis by using random-effects or fixed-effects models based on the heterogeneity of the included studies. Results: Eleven studies with a total of 500 patients fulfilled the inclusion criteria. We found no statistical significant difference in PFS between patients who developed hypothyroidism and patients without hypothyroidism during sunitinib therapy (HR: 0.82, 95% CI: 0.59-1.13, p-value = 0.22) (6 studies; 250 patients). For studies that included patients treated with either sunitinib or sorafenib, the development of hypothyroidism was found to be predictive for longer progression free survival (HR: 0.59, 95% CI: 0.42-0.84, p-value = 0.003) (3 studies; 205 patients). The HR for OS was 0.52 (95% CI: 0.31-0.87, p-value = 0.01) for patients who developed hypothyroidism during sunitinib therapy compared to patients without hypothyroidism (4 studies; 147 patients). Conclusions: The development of hypothyroidism during TKIs therapy is not clearly shown to be predictive in patients with mRCC. The observed advantage in overall survival for patients with treatment related hypothyroidism should be interpreted with caution due to the potential imbalance of treatments received after first line treatment in each group.
Are regional funding decisions resticting pharmaceutical research and development in metastatic renal cell carcinoma (mRCC)?
Authors: Conter Henry Jacob 
Published: February 2017

506 Background: Targeted therapy has revolutionized the treatment of mRCC. However, cost has lead to variable regional approval and funding. Can such variation in funding of established drugs impede approval of newer agents? Methods: Regulatory agency decisions regarding axitinib, the most recently approved mRCC therapy in the U.S., were reviewed. Reports from the US Food and Drug administration (FDA), the European Medicines Agency (EMA), the pan-Canadian Oncology Drug Review (pCODR), UK's National Institute for Health and Care Excellence (NICE), and the Therapeutic Goods Administration (TGA) of Australia were included. Data abstracted included the date of report publication, basis for determination of clinical efficacy, determination of cost-effectiveness, theme of stakeholder submissions prior to and after the regulatory decision, final decision, and rational for approval/rejection. Results: At the time of analysis, all agency decisions had been finalized. All of the agencies based their assessment of clinical efficacy of primarily on the same phase III clinical trial: the AXIS trial, demonstrating a progression-free survival benefit of axitinib compared to sorafenib (6.7 versus 4.7 months, p<0.001). Cost-effectiveness data was considered by NICE and pCODR, but not the FDA, the EMA, or the TGA. Axitinib was recommended received approval by the FDA, the EMA, and the TGA for use in patients with mRCC who have failed prior treatment with sunitinib or cytokines. pCODR recommended axitinib for funding in the 2nd line setting only in patients unable to tolerate everolimus. And NICE recommended against the funding of axitinib. Both dissenting organizations cited concerns with the pivotal trial’s control arm, sorafenib, not representing their regional standards of care as primary reasons for restricted access and rejection. Cost considerations were also cited as factors in the rejections. Conclusions: Differing regulatory approvals and funding worldwide are creating regional standards of care that impeding the research, development, and approval of newer agents. Divergent standards of care before and after clinical trials may restrict their external validity and applicability.
Retrospective evaluation of tyrosine kinase inhibitor (TKI)-everolimus (eve) and/or TKI-eve-TKI sequences in metastatic renal cell carcinoma (mRCC): A French survey—The sector study.
Authors: Oudard Stephane , Joly Florence , Geoffrois Lionnel , Laguerre Brigitte , Houede Nadine , Barthelemy Philippe , Gross-Goupil Marine , Yann-Alexandre Vano , Lucidarme Olivier , Bidault François , Kelkouli Nadia , Escudier Bernard 
Published: February 2017

509 Background: In the RECORD-1 study, only 22% of the mRCC patients (pts) received eve in pure 2nd line. Thus more data in real world are needed. A retrospective French survey, on a large patient population, was designed to evaluate efficacy for the sequence TKI-eve and/or TKI-eve-TKI in mRCC. Methods: Between 10/08 and 10/12, 164 mRCC pts from 26 french centers, who progressed on initial TKI and received eve as 2nd line were recorded. In these pts, 3rd line TKI was recorded. Primary endpoint was Duration of Treatment (DT) of each sequence. Secondary endpoints were best radiological response for eve evaluated by 2 independent radiologists, tolerability, dose reduction, overall survival from the start of first TKI (OS). Patients characteristics: Amongst 164 pts, 144 pts with follow-up > 4 months since initiation of eve were evaluated, 59/144 pts received TKI-eve-TKI. Before eve initiation: median age was 65 yrs, most pts were male (70.3%), had clear cell histology (92.3%), had received sunitinib as first TKI (94.4%). Main comorbidities were: hypertension (43.8%), diabetes (15.3%), and hypercholesterolemia (19.4%). At the time of eve initiation, MSKCC classification was good (24.4%), intermediate (61.5%) or poor (14.1%). Results: median DT of eve was 4 months and 21% pts were treated >9 months with 2.9% PR and 67.6% SD by central review. Correlation between response to first TKI and eve was observed. Dose reduction of eve for toxicity was 23.2%. The most common toxicities (all grades) were: stomatitis (25.3%), PNI (13%), fatigue (40.7%), hyperglycemia (9.3%), hypercholesterolemia (17.3%) and hypertriglyceridemia (22.8%). Median duration of TKI-eve sequence was 18 months (IC95%: 15-20), and OS was 36 months (IC95%: 27-56). For TKI-eve-TKI sequence (59 pts), sorafenib was mostly used (76.3%) with dose reduction and clinical benefit rate of 26.7% and 42.2% respectively. Median DT and OS were 24 and 41 months (IC95%: 19-29; 25-57) respectively. Conclusions: In real world experience, for mRCC pts receiving TKI-eve sequence, median DT of eve is 4 months with OS of 36 months which compares favorably with RECORD1 and RECORD 3 trials respectively.
Reliability of the CT-SCAN percutaneous biopsy for small renal masses.
Authors: Ingels Alexandre , Barret Eric , Audenet Francois , Lunelli Luca , Prada Costa Guilherme , Rozet Francois , Galiano Marc , Sanchez-Salas Rafael , Lenoir Stephane , Validire Pierre , Cathelineau Xavier 
Published: February 2017

514 Background: The aim of this study was to assess the veracity of the outcomes from renal biopsy performed under CT-scan control for patients harboring cT1a stage tumors. Methods: In a retrospective study, we analyzed the outcomes of renal biopsies performed under CT-scan control for patients harboring tumors under 4 cm. Pathology has been compared between biopsy sample and nephrectomy specimen. Every patient included had a small renal mass (cT1a) and had to undergo a CT-scan guided renal biopsy before nephron sparing or enlarged nephrectomy (that had to be done within 6 months after the biopsy). Results: From January 2007 to December 2012, we performed 79 CT-scan guided renal biopsies. Among these patients, biopsy lead to the diagnosis of the renal lesion for 70 cases. For 9 cases, biopsy was not contributive. Following the biopsy, 19 patients underwent a nephron sparing surgery and 10 a radical nephrectomy. Comparison of the pathological outcomes between biopsy and surgical specimen showed an agreement for the diagnosis of carcinoma in 28 cases (97%): one case of chromophobe carcinoma on biopsy sample analyze happened to be an oncocytoma on the surgical specimen. Sensitivity was 100% and Specificity 67%. Conclusions: Renal biopsy under CT-scan control yield to a trustful diagnosis of small renal mass in most of the cases. It seems relevant to systematically offer this strategy to the patients in order to adapt their following treatment.
Association of baseline health and gender with small renal mass pathology.
Authors: Bazzi Wassim , Dejbakhsh Sheila , Bernstein Melanie , Coleman Jonathan A. , Russo Paul 
Published: February 2017

515 Background: Previous reports describe that 20% of small renal masses (SRM) are benign and women are twice as likely to have benign pathology. In this study we further explore the association of baseline health and gender with SRM pathology. Methods: After IRB approval, retrospective chart review of patients who have undergone nephrectomy at Memorial Sloan-Kettering Cancer Center from 05/1998 to 10/2012 with final path ≤ 4cm and staged as pT1a if malignant. Tumor size ≤ 4cm was chosen to limit the tumor mass effect on renal function. Patients with solitary kidney, multiple and bilateral tumors, and history of prior renal surgeries were excluded. Collected data included age, gender, race, ASA class for medical co−morbidities which were divided into low (I−II) and high (III−IV), procedure, preoperative serum creatinine, eGFR, and final pathology. eGFR was calculated using the CKD−Epi formula. Preoperative Chronic kidney disease (pCKD) was defined as eGFR < 60 mL/min per 1.73 m2. Malignant pathologies were clear cell renal cell carcinoma (RCC), papillary RCC and chromophobe RCC whereas benign were oncocytoma, angiomyolipoma and other. Logistic regression analysis was performed to determine clinical factors associated with malignant SRM. Results: Our cohort consisted of 1726 patients with mean age 59.7 yrs. 61% (n=1045) were men, 90% (n=1,553) were white, 43% (n=736) had high ASA, 89% (1,540) underwent partial nephrectomy, 30% (n=525) had pCKD, 83% (n=1426) with malignant pathology and mean tumor size 2.5cm. On bivariable analysis patients with malignant SRM had a higher proportion of men (64.3 vs. 42.7%, p<0.001), high ASA class (43.8 vs. 37.3%, p=0.041) and larger tumors (2.6 vs. 2.3, p<0.001). There were no differences in age, race, mean eGFR or proportion with pCKD. On logistic regression analysis by gender factors associated with malignant pathology in women were high ASA class (OR 1.57, 95% CI 1.07−2.32) and tumor size (OR 1.48, 95% CI 1.20−1.81), and in men tumor size only (OR 1.33, 95% CI 1.06−1.67). Conclusions: Our results are in line with previous reports on the association of male gender and larger tumor size with malignant SRM. In addition we do show that among women those with poor health have a higher likelihood for having a malignant SRM.
Diabetes mellitus and risk of cancer-specific mortality among patients with clear cell renal cell carcinoma undergoing nephrectomy.
Authors: Psutka Sarah P. , Stewart Suzanne B. , Lohse Christine M. , Tollefson Matthew K. , Boorjian Stephen A. , Cheville John C. , Leibovich Bradley C. , Thompson R. Houston 
Published: February 2017

516 Background: The impact of diabetes mellitus (DM) on outcomes in patients with renal cell carcinoma (RCC) is controversial. Herein, we evaluated the association of DM with survival among patients with RCC. Methods: We reviewed 2,589 patients treated with nephrectomy for sporadic, unilateral, M0 RCC between 1990 and 2008 and compared demographic and tumor characteristics in patients with and without DM (nonDM). Patients with DM (n=313) were matched 1:2 to nonDM patients according to date of surgery, age, smoking status, obesity, ECOG performance status (PS), CKD stage, histological subtype, and nuclear grade. Cancer-specific (CSS) and overall survival (OS) were compared by Kaplan-Meier analysis. The association of DM with outcomes was evaluated with Cox proportional hazards regression models. Results: A total of 313 (12%) patients had DM. DM patients were significantly older at RCC diagnosis, more likely to be obese, and had higher Charlson scores, CKD class, rates of smoking, and worse PS at surgery (p<0.001). Patients with DM were also more likely to have ccRCC (83% vs. 76%, p=0.02) and to undergo nephron-sparing surgery (42% vs. 35%, p=0.01), while other pathologic features were similar in DM and nonDM. Among the 939 matched cases and controls, 463 patients died within a median of 5.5 years after nephrectomy. Median follow-up for survivors was 8.6 years. Five-year CSS was not significantly different among DM patients 84% vs. nonDM patients 87% (p=0.11), although 5-year OS was significantly worse among DM patients (66% vs. 75%; p<0.001). Indeed, even after adjusting for Charlson score, DM patients were noted to have a significantly increased risk of all-cause mortality (HR 1.33; p=0.004). In a subanalysis of patients with clear cell RCC, DM patients were more likely to die from RCC compared with nonDM patients after adjusting for the SSIGN (Stage, Size, Grade, Necrosis) score (HR 1.44; p=0.034). Conclusions: In this surgical cohort, DM was independently associated with decreased CSS among patients with ccRCC and with decreased OS in all RCC subtypes. Further studies to determine the potential biologic mechanism for this interaction are warranted.
Evaluating 18F-16β-fluoro-5α-dihydrotestosterone (FDHT) and FDG PET as prognostic biomarkers for patients (pts) treated with abiraterone acetate (AA).
Authors: Feldman Jarett Lawrence , Fox Josef J. , Autio Karen A. , Gavane Somali C. , Heller Glenn , Schöder Heiko , Humm John , Martinez Danny F. , Slovin Susan F. , Scher Howard I. , Larson Steven M. , Morris Michael J. 
Published: February 2017

56 Background: There are no available imaging biomarkers that can prognosticate for clinical outcomes for patients treated with AA. FDG and FDHT PET demonstrate glucose metabolism and androgen receptor expression, respectively. This is the first study of FDG and FDHT PET as a prognostic biomarker for pts treated with AA. Methods: Pts with progressive metastatic castration resistant prostate cancer (mCRPC) starting AA underwent FDG and FDHT PET scans on an imaging clinical trial. PSA, SUVmax (hottest slice of hottest lesion), and SUVmaxavg (average SUVmax of 5 index lesions) were collected. An SUV value of 1 was imputed for calculating SUVmaxavg in the absence of 5 index lesions. Imaging characteristics were compared to PFS, defined as time to radiographic progression, biochemical relapse or death. The Cox proportional hazards model was used to determine the association between the PET measurements and PFS. The statistics used to measure the association was the concordance probability estimate (CPE). Results: 24 scans sets were obtained. Median pt characteristics were: age 70 (48-85), Gleason score 8 (range 6-10), PSA 85 (2-459). Radiographic and PSA progression occurred in 15/24 (63%), radiographic only 4/24 (17%), and biochemical only 2/24 (9%). 1 pt died on study, 1 elected to discontinue tx, and 1 remains on AA. 16/24 (67%) and 18/24 (75%) of FDG and FDHT PET scans respectively had ≥ 5 hypermetabolic lesions. Median FDG SUVmax was 8 (2-15), FDG SUVmaxavg 5 (1-11), FDHT SUVmax 11 (3-28) and FDHT SUVmaxavg 7 (1-16). The correlation between PET measurements and PFS is described (Table). Conclusions: Preliminarily, baseline FDG SUVmax and SUVmaxavg appear to be prognostic for PFS in pts treated with AA. Higher SUV values prognosticate for a shorter time to progression. Further evaluations of FDG/FDHT PET in mCRPC are underway to better define the role each modality has as a prognostic and response biomarker for AA. Clinical trial information: NCT00588185. [Table: see text]
Pattern of occult nodal relapse diagnosed with 18F fluoro-choline PET/CT in prostate cancer patients with biochemical failure after prostate-only radiotherapy.
Authors: Lepinoy Alexis , Cochet Alexandre , Cueff Adele , Cormier Luc , Martin Etienne , Maingon Philippe , Bosset Jean Francois , Brunotte Francois , Crehange Gilles 
Published: February 2017

77 Background: 11C or 18F-labeled choline PET/CT has led to better understanding of the lymph drainage pattern of prostate cancer. It can provide radiation oncologists with maps to guide the delivery of prophylactic pelvic radiotherapy while minimizing radiation toxicity to non-target normal tissue with intensity modulated radiation therapy (IMRT). The purpose of this study was twofold: (1) to describe the pattern of nodal relapse in prostate cancer patients with biochemical failure after prostate-only radiotherapy; and (2) to determine whether patients with 18F-fluoro-choline (FCH) PET/CT positive nodes experienced treatment failure within the clinical target volume (CTV) defined by the RTOG guidelines (CTVRTOG). Methods: Between July 2008 and December 2012, 83 patients with a prostate cancer had a FCH PET/CT for biochemical failure after radiotherapy. Of 65 patients with FCH-positive findings, 33 had positive nodes. This analysis included 31 patients who had undergone prior prostate-only radiotherapy or radical prostatectomy followed by local radiotherapy. Each choline FCH positive node was assigned to a lymph node station and situated with regard to the CTVRTOG. Results: Fourteen patients (45.2%) had a relapse outside the CTVRTOG. Of the 17 patients with a positive node inside the CTVRTOG, 15 had a single node (88.2%) while seven patients out of the 13 evaluable patients (53.9%) who had a relapse outside the CTVRTOG had two or more positive nodes on FCH PET/CT. Patients with FCH+ nodes outside the CTVRTOG were more likely than patients with FCH+ nodes inside the CTVRTOG to have two or more involved nodes (OR= 8.75, [95% CI: 1.38-54.80], p= 0.020). The ventral part of the external iliac station (29.0%) was the main site of relapse inside the CTVRTOG whereas relapses that occurred outside the CTVRTOGinvolved the proximal common iliac (19.3%) and lower periaortic nodes (19.3%) up to L2-L3. Conclusions: Nearly half of the patients had FCH+ nodes outside the CTVRTOG with a significantly higher number of nodes involved outside the CTVRTOG. Three-dimensional mapping of nodal relapses evaluated with FCH PET/CT suggests that with IMRT the upper field limit of pelvic radiotherapy could be extended to L2-L3 safely to cover 95% of nodal stations at risk of an occult relapse.
Degarelix monotherapy versus luteinizing hormone-releasing hormone (LHRH) agonists plus antiandrogen flare protection in the treatment of men with advanced prostate cancer.
Authors: Tombal Bertrand , Damber Jan-Erik , Malmberg Anders , Persson Bo-Eric , Klotz Laurence , Iversen Peter 
Published: February 2017

86 Background: Short-term antiandrogen (AA) flare protection is used to counter the testosterone surge associated with luteinising-hormone-releasing hormone (LHRH) agonist therapy. Degarelix, a gonadotrophin-releasing hormone antagonist, does not cause testosterone surge. Data from two phase III trials have been used to compare the one year efficacy of degarelix monotherapy versus combined agonist plus AA flare protection. Data has reported testosterone surge in agonist patients despite AA therapy, as well as improved prostate-specific antigen (PSA) progression-free survival (PFS) and lower mortality in degarelix patients. Here we focus on PSA PFS outcomes and serum alkaline phosphatase (S-ALP) in high risk patients (metastatic disease or PSA more than 50 ng/mL). Methods: Data were pooled from two randomised, one-year studies; CS21 compared monthly degarelix with leuprolide and CS35 compared 3 month formulations of degarelix and goserelin. AA was administered in the agonist groups at the investigator’s discretion. Analyses were performed by the Kaplan-Meier method and Log-rank test (probability of PSA PFS), Cox regression (adjusted hazard ratios [HR] for PSA PFS failure) and repeated measures ANCOVA (S-ALP). Results: Nine hundred seventy four patients received degarelix and 69 patients agonist plus AA. The agonist plus AA group contained a higher proportion of patients with Gleason score 7 to 10, metastatic disease, or baseline PSA more than 50 ng/mL compared with the degarelix group. Cox regression was used to account for these baseline differences. PSA PFS failure rate for metastatic patients and those with baseline PSA more than 50 ng/mL was significantly lower with degarelix than with agonist plus AA (HR=0.516, p=0.0198 and HR=0.490, p=0.0077, respectively). S-ALP levels in metastatic patients and those with baseline PSA more than 50 ng/mL during the year of treatment were significantly lower with degarelix (p=0.0025 and 0.0005, respectively). S-ALP fell below baseline by 2 months or less with degarelix and 7 months or less with agonist plus AA. Conclusions: This pooled analysis indicates LHRH agonist plus AA therapy flare protection may not achieve similar disease control as degarelix monotherapy during the first year of therapy in patients at high risk of symptomatic disease progression.
Multidisciplinary clinic evaluation changes prostate cancer stage and risk stratification.
Authors: Sundi Debasish , Cohen Jason , Cole Alexander , Neuman Brian , Cooper Jack , Faisal Farzana , Raben Marian , Song Danny Y. , Drake Charles G. , Netto George J. , Macura Katarzyna , DeWeese Theodore L. , Partin Alan Wayne , Ross Ashley E. , Schaeffer Edward M. 
Published: February 2017

91 Background: The use of multidisciplinary clinics (MDCs) for outpatient cancer evaluation is increasing. Data on whether MDCs improve prostate cancer (PCa) care are limited. We studied the frequency of changes in PCa grade and stage upon MDC evaluation. Methods: Between May 2008 and December 2012, 887 consecutive patients underwent consultation for newly diagnosed prostate cancer at the Johns Hopkins Hospital (JHH) MDC, which features real-time collaboration among urologists, radiation oncologists, and medical oncologists. Retrospective chart review identified presenting tumor characteristics, based on outside assessment (medical records sent upon referral to MDC), as compared with disease stage and grade as determined at MDC evaluation. All outside biopsy slides were reviewed by JHH pathologists, and all outside imaging (CT, MRI, bone scan) was reviewed by JHH radiologists. Results: The three most chosen treatments after MDC evaluation were external beam radiotherapy +/- androgen deprivation (39.3%), radical prostatectomy (32.0%) and active surveillance/expectant management (12.9%). Using the NCCN guidelines as a benchmark, many men were found to have undergone non-indicated imaging (bone scan 23.9%, CT/MRI 47.4%). Overall, 186/647 (28.7%) had a change in their NCCN risk classification or N or M stage. For example, 2.9% of men were down-classified as very-low-risk, rendering them eligible for active surveillance. 5.7% of men thought to have localized cancer were up-classified as metastatic, thus prompting systemic management approaches. Conclusions: Comprehensive evaluation of prostate cancer patients in a MDC is associated with critical changes in presenting disease classification from baseline in over one in four men. While questions about the long term costs and benefits of MDCs remain, these results lend credence to the growing belief that MDCs may dramatically impact management for a large number of men with prostate cancer. [Table: see text]