bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of rapid disease progression in the treatment break following cytoreductive nephrectomy (CN) after presurgical sunitinib in patients with primary metastatic renal cell carcinoma (RCC).
Authors: Bex Axel , Powles Thomas , Blank Christian U. , Chowdhury Simon , Horenblas Simon , Peters John , Boleti Ekaterini , Haanen John B. A. G. 
Published: March 2020

4611 Background: There is concern that interruption of tyrosine kinase inhibitors (TKI) triggers disease progression (PD) and metastasis. This is based on preclinical models and observation of rapid PD in the postsurgical treatment break in patients pretreated with TKI. Little is known about the frequency of PD during postsurgical TKI interruption and its outcome. These data may have implications for neoadjuvant or presurgical treatment concepts. Methods: Of 66 patients from two closed phase II trials investigating 2-3 months presurgical sunitinib for primary metastatic clear-cell RCC, 45 were evaluated in this retrospective analysis because they had absence of PD prior to planned surgery and underwent CN (35 [78%] MSKCC intermediate and 10 [22%] poor risk). Patients had CT scans at the end of pretreatment and at 4 weeks post-nephrectomy before restarting sunitinib. In patients with postsurgical RECIST PD at 4 weeks when compared to the preoperative CT scan overall survival (OS) was measured from the time of nephrectomy and compared to patients without treatment break PD. Results: Median OS of 45 patients from the time of surgery was 22 months (13.0-31.5 months). Overall 14 patients progressed during treatment break (31%), with new sites of disease in 5/14 (35%). Reintroduction of sunitinib resulted in disease stabilisation or better in 13. Patients with poor risk were represented in the progressors (n=4[28%]) and non-progressors (n=6 [19%]) (p=0.7 fishers exact test). The hazard ratio (HR) for death associated with PD during treatment break was 1.90 (95% CI 0.89-4.08). OS for non-progressors was 25 months (15-NA) and 13 months (6-27) for progressors. Conclusions: A significant proportion of patients develop PD upon sunitinib withdrawal in a 4 week recovery period following CN. In view of the small sample size these data suggest a strong trend toward treatment break PD being associated with a poor outcome. It is not clear whether this PD is related to interruption of TKI, surgery or a combination of factors. The EORTC SURTIME trial investigates treatment break PD after immediate CN and CN after sunitinib and may answer this question.
Adherence to oral anticancer drugs (OAD) in patients (pts) with metastatic renal cancer (mRCC): First results of the prospective observational multicenter IPSOC study (Investigating Patient Satisfaction with Oral Anti-cancer Treatment).
Authors: Wolter Pascal , Hendrickx Tine , Renard Vincent , Mebis Jeroen , Debruyne Philip R. , Wynendaele Wim , Schallier Denis C. C. , Vermeij Joanna , Nielander Aldrik , Machiels Jean-Pascal H. , Rottey Sylvie , Delande Stephanie , Goeminne Jean-Charles , Schoffski Patrick , De Coster Sandra , Lacour Valerie , Foulon Veerle 
Published: March 2020

4622 Background: Patient adherence to oral therapy is a critical issue in cancer treatment. The aim of this study is to investigate the prevalence and severity of non-adherence to OAD in mRCC and to identify factors predictive of non-adherence. Methods: Prospective observational multicenter trial performed at 11 Belgian academic and non-academic centers. All pts with mRCC starting OADs (sunitinib, pazopanib, everolimus or sorafenib) are eligible for the study. Pts are contacted by phone at baseline and at 1, 3, 6 and 12 months. At each contact, pts are asked to complete questionnaires investigating 1) medication adherence (MMAS), 2) patient satisfaction with treatment (CTSQ) and with treatment education (PS-CaTE), 3) the extent of information desire (EID), 4) quality of life (FACT-G and FKSI) and 5) the role of the pharmacist (SWiP). Adherence is measured using an electronic medication event monitoring system (MEMS, Aardex). Results: Between 02/2011 and 11/2011, 49 pts (m: 33, f: 16) with a median age of 63 years (range 25 - 87) have participated in the IPSOC study. Twenty-nine pts (64%) were treated with an OAD in first-line, 15 pts (33%) in second-line. With a median follow-up of 131 days (range 2 - 313) 45 pts (92%) claimed to be fully adherent to their treatment (based on MMAS and CTSQ data). Four patients indicated to have missed at least one dose, of whom two indicated they occasionally forgot their medication and two others interrupted treatment because of side effects. Based on MEMS data, mean adherence, defined as the percentage of days with at least the prescribed number of dosage taken, was 98.91%. Conclusions: The IPSOC study, the first to examine adherence to OAD among mRCC pts, shows that mRCC pts are almost fully adherent to treatment recommendations. This seems to be in contrast to adherence data for other, long-lasting, anti-cancer treatments. Further investigations will focus on the question whether extensive counseling and participation in side-effect programs contribute to the high percentage of adherence in this study.
Updated safety results from EXIST-2: Everolimus therapy for angiomyolipoma (AML) associated with tuberous sclerosis complex (TSC) or sporadic lymphangioleiomyomatosis (sLAM).
Authors: Bissler John , Kingswood Christopher , Zonnenberg B. A. , Frost Michael , Belousova Elena , Radzikowska Elzbieta , Sauter Matthias , Nonomura Norio , Brakemeier Susan , de Vries Petrus , Klimovsky Judith , Shah Gaurav D. , Miao Sara , Lincy Jeremie , Budde Klemens 
Published: March 2020

4632 Background: EXIST-2 (NCT00790400) is a randomized, double-blind, placebo-controlled, phase 3 trial assessing the efficacy and safety of everolimus, an oral mTOR inhibitor, for treating AML in patients with TSC or sLAM. We have previously reported that everolimus resulted in a significantly higher AML response rate vs placebo (41.8% vs 0%; 95% CI: 23.5–58.4; p<0.0001) with a consistent safety profile (Bissler et al. J Am Soc Nephrol. 22, 2011, Abstract LB-PO3159). Here we present a 90-day safety update. Methods: 118 eligible patients were randomized 2:1 to receive everolimus 10 mg daily (n=79) or placebo (n=39). The primary efficacy endpoint was AML response rate (proportion of patients with best overall AML response status of “response”). Original cut-off date for data analysis was 30 Jun 2011. An updated analysis of the safety data for the safety set (all patients receiving ≥1 dose of double-blind study drug with a valid post-baseline assessment) to 14 Oct 2011 are presented here. Results: As of 14 Oct 2011, median treatment duration was 48.1 and 45.0 weeks for everolimus and placebo arms, respectively. Discontinuations in the double-blind period were the same in the everolimus arm as the initial analysis, but had increased by 4 patients in the placebo arm since initial analysis (3 due to disease progression, 1 withdrew consent). The majority of adverse events (AEs) continued to be grade 1 or 2; the incidence of serious AEs was slightly higher than initially reported, particularly in the placebo arm (everolimus 20.3%, placebo 23.1%). AE incidence leading to discontinuation was the same as initially reported (everolimus 3.8%, placebo 10.3%). In the updated data, 3 additional everolimus patients required dose interruption or reduction due to AEs; dose reduction/interruption remained more common in the everolimus arm (51.9% vs. 20.5%). Conclusions: Overall, the 90-day updated safety data analysis from the EXIST-2 trial has not revealed any additional safety concerns. No other patients receiving everolimus withdrew for any reason, whereas 3 more patients receiving placebo withdrew due to disease progression.
Proton radiotherapy for prostate cancer in the Medicare population: Patterns of care and comparison of early toxicity with IMRT.
Authors: Yu James B. , Soulos Pamela R. , Cramer Laura D. , Roberts Kenneth B , Herrin Jeph , Potosky Arnold L. , Gross Cary P. 
Published: March 2020

4651 Background: Proton radiotherapy (PRT) is a costly treatment used for prostate cancer despite little evidence supporting its use. We examined patterns of PRT use in the Medicare program and assessed the short-term toxicity of PRT vs. intensity modulated radiation therapy (IMRT). Methods: Using national Medicare claims from 2008-2009, we identified a sample of prostate cancer patients ages 66-94 who had received PRT or IMRT. We used multivariable logistic regression to identify patient and regional factors associated with receipt of PRT. We searched claims for procedure and diagnosis codes indicative of treatment-related complications and grouped the complications into genitourinary (GU), gastrointestinal (GI), and other complications. To compare the effect of PRT and IMRT on short-term toxicity, we used a Mahalanobis distance approach to match each PRT patient to two IMRT patients, achieving balanced distribution of clinical and sociodemographic characteristics. We compared six-month and one-year outcomes between the two treatment groups using conditional logistic regression. Results: We identified 27,647 men; 421 (2%) received PRT and 27,226 (98%) received IMRT. Patients who received PRT were widely geographically distributed, with some patients traveling >500 miles for treatment. PRT patients were younger, healthier, and of higher socioeconomic status. Although PRT was associated with a significant reduction in GU complications at six-months compared with IMRT (6.1% vs. 12.0%, OR 0.60 [95% CI 0.38-0.96], p=0.03), at one-year post-treatment there was no longer any difference in cumulative complication rates (18.9% vs. 21.9%, OR 0.96 [95% CI 0.61-1.53], p=0.88). There was no significant difference in GI or other complications at six-months or one-year post-treatment. Conclusions: Although PRT remains a scarcely used treatment, some prostate cancer patients traveled great distances for treatment. While PRT was associated with a reduction in six-month GU toxicity, there were no differences in toxicity at one-year. Further study on longer-term effects and other clinical and patient-reported outcomes is needed to inform the widespread application of PRT.
Liver metastases (LM) to predict for short overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC) patients (pts).
Authors: Kelly William Kevin , Halabi Susan , Carducci Michael Anthony , George Daniel J. , Mahoney John Francis , Stadler Walter Michael , Morris Michael J. , Kantoff Philip W. , Monk J. P. , Small Eric Jay ,   Alliance for Clinical Trials in Oncology
Published: March 2020

4655 Background: Patients withCRPC with LM represent a subset of patients with a poor prognosis. An exploratory analysis was performed to evaluate the difference in baseline characteristics and clinical outcomes in patients with and without LM from a randomized phase III trial (CALGB 90401) in men with mCRPC. Methods: Data from 1,050 men treated with docetaxel, prednisone with either bevacizumab or placebo were used. Pts were chemotherapy naïve, and had evidence of progressive mCRPC despite castrate testosterone levels and anti-androgen withdrawal, ECOG performance status ≤ 2, and adequate bone marrow, hepatic and renal functions. The proportional hazards model was used to assess the prognostic significance of LM in predicting OS and progression free survival (PFS) adjusting for stratification factors. Results: Fifty-nine (5.6%) of the 1045 pts with a complete data set had documented LM. Patients with LM had higher baseline alkaline phosphatase (ALK, 167 vs 117 U/L, p =0.0205) and lactate dehydrogenase (LDH, 262 vs 205 U/L, p =0.0001) compared to patients without LM. There were strong associations between LM status and lung metastasis (p=0.0004) and other visceral disease (p=<0.001) but not with bone disease. Clinical outcomes as a function of LM status are listed in the table. The median OS time in LM pts was 14.4 compared to 22.6 months, with a hazard ratio (HR) 1.4. The HR for treatment effect (DP+B vs. DP) for LM was not statistically significant for either group. Conclusions: Compared to pts without LM, mCRPC with LM are characterized by higher LDH and ALK and have a poor OS despite having similar PFS and objectivebiochemical response to docetaxel based therapy. [Table: see text]
Prostate-specific antigen (PSA) screening in the United States: Patterns of use and PSA outcomes in screened versus unscreened men.
Authors: Allen Ian M. , Hendrix Laura H , Royce Trevor Joseph , Stokes William A. , Wang Andrew , Godley Paul Alphonso , Chen Ronald C. 
Published: March 2020

4658 Background: PSA screening is a subject of substantial controversy. We examined patterns of PSA screening using a recent cohort from the population-based National Health and Nutrition Examination Survey (NHANES) study and compared PSA levels of previously screened vs. never screened men. Methods: NHANES is a cross-sectional study which collects health-related information (including cancer screening history, family history and socioeconomic variables) and blood samples from nationally representative samples of the US population. We included 2,078 previously screened men and 1,902 never screened men surveyed from 2003-8. Statistical analysis accounted for sampling weights. Results: 25% of men age 40-49 years had prior PSA screening; 56% age 50-59, and 72% age 60-69. Screening rates were higher for men with family history (68% vs. 50% no history, p<.001), health insurance (58% vs. 21% no insurance, p<.001), and Caucasians (59% vs. 44% non-Caucasian, p<.001). No significant differences were seen in the PSA values of screened vs. never screened men stratified by age (Table), or by race/ethnicity, insurance status, or family history. Conclusions: Rates of PSA screening in the US differ by age, family history, race/ethnicity and insurance status. However, no significant differences were seen in PSA values of screened vs. unscreened men, and very few patients under 60 years of age had PSA values ≥10. Despite questions about the appropriate role of PSA testing, population-based prostate cancer screening is routinely conducted among Caucasian and non-Caucasian men 50 years of age and older. [Table: see text]
Association of decreased expression of protein phosphatase 2A subunit PR55γ (PPP2R2C) with an increased risk of metastases and prostate cancer-specific mortality.
Authors: Spencer Elysia Sophia , Bluemn Eric Gregory , Johnston Richard , Zhang Xiaotun , Gordon Ryan Robert , Lewinshtein Daniel , Lucas Jared , Nelson Peter , Porter Christopher R. 
Published: March 2020

4669 Background: The protein phosphatase 2A (PP2A) holoenzyme complex negatively controls cell growth, differentiation and apoptosis. Down regulation of PP2A activity is associated with oncogenic transformation of papillomas and is a target for the small-T viral oncogene. The PR55γ (2R2C) subunit regulates PP2A target specificity, inhibiting c-Src activity in some cell lines. c-Src activity enhances growth and invasion in prostate cancer. This study evaluates whether PPP2R2C protein levels in radical prostatectomy (RP) specimens were predictive for the development of metastases or prostate-cancer specific mortality (PCSM). Methods: From 1954-1997, 1004 consecutive patients underwent RP at Virginia Mason Medical Center in Seattle. Metastases were confirmed radiographically or by tissue diagnosis. Death certificates confirmed PCSM. Patients without stored tissue were excluded. 34 patients with metastases or PCSM were matched to patients without recurrence (NR) at a 1:2 ratio. Paraffin-embedded tissue was stained with anti-PPP2R2C monoclonal antibody, clone 6D1 (Abnova, Taiwan). A pathologist evaluated the percentage and intensity of nuclei stained using a 4-point scale. Statistical analysis was performed on SAS. Results: Mean follow up was 10.26 years. PPP2R2C was detected in 13/18 (72.2%) PCSM, 18/22 (81.8%) metastases and 45/49 (91.8%) NR patients. Mean expression was lower in cancerous vs benign glands, 1.74 vs 2.04 (p = 0.001). Expression intensity from PCSM vs NR was 1.45 vs 1.80 (p = 0.041). On multivariate analysis, expression was lower in metastases or PCSM versus NR 1.79 vs 2.35 (p = 0.002), independent of pre-op PSA and Gleason grade. Conclusions: PPP2R2C loss was highly correlated with metastasis and PCSM. Patients with the lowest levels of expression were at the highest risk for PCSM. As tissue was obtained at time of surgery, this analysis reflects a truly prognostic biomarker, independent of Gleason grade and PSA. We have shown that PPP2R2C scoring is a useful metric to identify patients at high risk of developing advanced disease. With further validation may allow for more accurate individual patient treatment plans and counseling.
Prospective assessment of cost, morbidity, and survival associated with lymphadenectomy in low-risk endometrial cancer.
Authors: Dowdy Sean Christopher , Borah Bijan J , Bakkum-Gamez Jamie Nadine , Weaver Amy , McGree Michaela , Haas Lindsey R , Martin Jan , Keeney Gary L. , Mariani Andrea , Podratz Karl C. 
Published: March 2020

5004 Background: Since 1999, patients with low-risk endometrial cancer (EC) as defined by the Mayo criteria have preferably not undergone lymphadenectomy (LND) at our institution. We assess survival, sites of recurrence, morbidity, and cost per up-staged case in this low-risk cohort. Methods: Consecutive patients with Mayo-defined low-risk EC managed without (non-LND) and with LND were compared. Cause-specific survival (CSS) was estimated using the Kaplan-Meier method and compared using the log-rank test. 30-day cost analyses were equated to 2010 Medicare dollars. Results: Among 1,393 consecutive surgically managed EC cases, 385 (27.6%) met the Mayo low-risk criteria, accounting for 34.1% of type I EC. The 5-year CSS of the low-risk cases was 98.6 %. There were 80 LND cases (median # nodes, 29) and 305 non-LND cases. Complications within 30 days occurred in 37.5% and 19.3% of LND and non-LND cases, respectively (P<0.001). Nodal metastasis was identified in a single LND case (1.3%). There were 11 recurrences, 6 of which were vaginal. Not a single recurrence was detected in the pelvic or paraaortic nodal areas in these 385 patients, with a median follow-up of 5.4 years. The estimated prevalence (combining surgery and surveillance) of lymph node metastasis was 0.3%. The 5-year CSS in LND and non-LND cases was 97.3% and 99.0%, respectively (P=0.32). Patients were more than seven times as likely to die of co-morbidities than from EC. The 30-day median cost of care was $15,678 for LND cases compared to $11,028 for non-LND cases (P<0.001). The estimated cost per up-staged low-risk case was $439,990 if performed via endoscopy and $327,866 via laparotomy. If the 305 non-LND cases had been subjected to LND, an estimated additional $1,418,189 would have been expended. Conclusions: For patients with low-risk EC as defined by the Mayo criteria, lymphadenectomy dramatically increases morbidity and 30-day cost of care without discernible short- or long-term benefits: CSS was 99% with a 0.3% rate of nodal metastasis. In these low-risk patients, hysterectomy with salpingo-oophorectomy alone is appropriate surgical management and should be standard of care.
A randomized, phase III trial of paclitaxel plus carboplatin (TC) versus paclitaxel plus cisplatin (TP) in stage IVb, persistent or recurrent cervical cancer: Japan Clinical Oncology Group study (JCOG0505).
Authors: Kitagawa Ryo , Katsumata Noriyuki , Shibata Taro , Nakanishi Toru , Nishimura Sadako , Ushijima Kimio , Takano Masashi , Satoh Toyomi , Yoshikawa Hiroyuki , Kamura Toshiharu ,   Japan Clinical Oncology Group
Published: March 2020

5006 Background: TC is a less toxic regimen in terms of milder nephropathy, neuropathy and no need of hospitalization. This multicenter phase III trial was designed to evaluate the clinical benefits of TC compared with TP which is current standard chemotherapy for stage IVB or recurrent cervical cancer. Methods: Patients (pts) with stage IVB or recurrent cervical cancer; not amenable to curative therapy; 0-1 prior platinum; no prior taxanes; were randomized with minimization method to either TP (T 135 mg/m2 24h d1 + P 50 mg/m2 2h d2) or TC (T 175 mg/m2 3h d1 + C AUC5 1h d1), both for maximum 6 cycles every 21 days. Primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), toxicities, and the proportion of non-hospitalization periods (NHP) as a surrogate for QoL. The trial was powered at least 70% to confirm the non-inferiority of TC to TP (threshold hazard ratio [HR] 1.29) in terms of OS, and the planned sample size was 250 pts with one-sided alpha 5%. HR is estimated by a stratified Cox regression. Results: From 2/06 to 11/09, 253 pts were enrolled. 71% pts of TP arm and TC arm each received 6 cycles. Median follow-up is 17.4 mo. Results are as below. As an alpha level for an interim analysis was less than 0.0001, significance level for the final analysis is approximately 5% even after the multiplicity adjustment. Conclusions: This first randomized controlled trial comparing carboplatin doublet with cisplatin doublet showed significant non-inferiority of TC in terms of OS. More feasible and less toxic TC can be recommended as the new standard treatment for stage IVB or recurrent cervical cancer. [Table: see text]
Survival after radiation therapy for early-stage endometrial carcinoma: The Oslo study revisited after up to 43 years of follow-up.
Authors: Lindemann Kristina , Onsrud Mathias , Kristensen Gunnar , Trope Claes 
Published: March 2020

5008 Background: There is an ongoing debate regarding the benefit of radiation in patients with early stage endometrial carcinoma. Data on long time risk conferred by radiation is scarce. This study is a long-term follow-up on survival and secondary cancers of a previously published randomized study (Aalders J. et al., Obstet Gynecol 1980; 56: 419-27). Methods: Between 1968 and 1974, 568 patients with endometrial cancer FIGO stage I primarily treated with abdominal hysterectomy and bilateral salpingo-oophorectomy were included in the study. Patients were postoperatively randomized to receive either vaginal radium brachytherapy followed by external pelvic radiation 40 Gy (N=288) or brachytherapy alone (N=280). Survival data and data on incident secondary cancers were obtained by individual linkage to the Registry of Statistics Norway and Cancer Registry of Norway. By the end of follow-up at 1 November 2011, 45 (7.9%) patients were still alive. We used Cox proportional hazards model to estimate hazard ratios (HR) with 95% confidence intervals (95% CI). We also conducted analyses stratified by age groups. Results: After median 21 (range 0-43.4) years of follow-up there was no significant difference in overall survival or relapse free survival between treatment arms with HR of 1.12 (95% CI: 0.95-1.33) and HR 0.88 (95% CI: 0.55-1.40), respectively. Patients treated with external radiation had significantly lower risk of developing locoregional relapse (p<0.001). However, women younger than 60 years had a significant poorer survival after external radiation (HR 1.36; 95% Cl: 1.06-1.76). In this patient group the risk of secondary cancer was significantly increased (HR 1.9; 95% CI: 1.23-3.03). Conclusions: We observed no survival benefit of external pelvic radiation in early stage endometrial carcinoma. In women younger than 60 years, pelvic radiation decreased survival, probably due to increased risk of subsequent second neoplasms. Adjuvant external radiotherapy cannot be recommended to this patient group. Those who have received such treatment might eventually benefit from prolonged post treatment surveillance with respect to secondary cancer.