bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 2 biomarker-driven study of ipilimumab plus nivolumab (Ipi/Nivo) for ARV7-positive metastatic castrate-resistant prostate cancer (mCRPC).
Authors: Boudadi Karim , Suzman Daniel L. , Luber Brandon , Wang Hao , Silberstein John , Sullivan Rana , Dowling Donna , Harb Rana , Nirschl Thomas , Dittamore Ryan Vance , Carducci Michael Anthony , Eisenberger Mario A. , Haffner Michael , Meeker Alan , Eshleman James R. , Luo Jun , Drake Charles G. , Antonarakis Emmanuel S. 
Published: September 2018

5035 Background: ARV7+ mCRPC is an aggressive phenotype with a median PFS of 3-4 mo and OS of 7-9 mo. We hypothesized that ARV7+ tumors would be enriched for DNA repair mutations, rendering them more responsive to combined immune checkpoint blockade. Methods: We enrolled 15 mCRPC pts with ARV7+ CTCs (using a CLIA-certified assay) into a single arm phase 2 study. Pts received Nivo 3 mg/kg plus Ipi 1 mg/kg every 3 wk x 4 doses, then maintenance Nivo 3 mg/kg every 2 wk. Targeted sequencing for DNA repair defects was performed on pretreatment tumor biopsies (n=11) or cell-free DNA (n=4). Primary endpoint: PSA50response rate. Secondary endpoints: objective response rate (ORR) in pts with measurable disease, durable PFS (lack of progression ≥24 wk), PSA‐PFS, radiographic (r)PFS, overall survival (OS), and frequency/intensity of AEs. Results: 15 ARV7+ men were enrolled, with median f/u 8.4 (range 1.9–10.5) mo. Median age was 65, 47% had ECOG ≥1, median PSA was 115 ng/mL, 67% had visceral/nodal mets, all had bone mets, and 60% had ≥4 prior regimens for mCRPC. Mean ARV7/AR ratio was 23% (range 3–75%). 6/15 men (40%) had pathogenic DNA repair gene mutations ( BRCA2, ATM, MSH6, FANCM, FANCA, POLH). Overall, the PSA50rate was 1/15 (7%), ORR was 2/8 (25%), durable PFS rate was 3/15 (20%), PSA-PFS was 3.0 (95%CI 2.1–4.9) mo, rPFS was 3.9 (95%CI 2.8–5.5) mo, and OS was 9.5 (95%CI 7.2–NA) mo. Outcomes appeared better in DNA repair deficient (DRD+) tumors vs. DNA repair proficient (DRD–) tumors (TABLE). 15 grade 3-4 treatment-related AEs occurred in 7/15 (46%) men (including 2 hepatitis, 2 colitis, 1 pneumonitis); there were no treatment-related deaths. Conclusions: In this first study targeting ARV7+ mCRPC, treatment with Ipi/Nivo had acceptable safety and encouraging efficacy, particularly in men with DRD+ tumors. DNA repair mutations may be enriched in ARV7+ prostate cancer. Clinical trial information: NCT02601014. [Table: see text]
Clinical implications of the 2012 US Preventive Services Task Force (USPSTF) PSA screening recommendation in prostate cancer diagnoses and 5-year survival at a Minnesota safety net health care system.
Authors: Gale Kevin , Pease Daniel Fellows , Guinness Joseph , Wiernik Andres 
Published: September 2018

5051 Background: Prostate specific antigen (PSA) screening for prostate cancer has declined following the USPSTF 2012 recommendation. How screening rates and prostate cancer diagnoses have subsequently changed in a racially diverse patient population is not well defined. In this study, we aim to determine the impact of the USPSTF screening recommendation in the Hennepin Healthcare System (HHS) in the state of Minnesota. Methods: A single-institution retrospective analysis of data from our electronic health record, to identify the characteristics of PSA screening and new prostate cancer diagnoses for men ≥50 years between 2008 and 2015. Data before and after May 2012 were compared. P-values were calculated using binominal and generalized linear models. Results: Nearly 22,000 patients underwent PSA screening from 2008 to 2015. PSA screening rates decreased after May 2012 for the four largest demographics represented (p < 0.001). Hispanics and Blacks were more likely to be screened when compared to Whites and Asians (p < 0.05). 319 cases of prostate cancer were diagnosed from 2008 to 2015 with 87 cases (27.3%) diagnosed by PSA-screening. The number needed to screen to diagnose one patient with prostate cancer at HHS was 137.5, and 9.5% of patients (1146 patients) had a false positive PSA that led to further testing or a biopsy. $56,090 was spent in screening costs per diagnosis of early stage prostate cancer via screening. Patients diagnosed from screening were less likely to present with high Gleason scores (8-10) compared to non-screening diagnosis (8% vs 23.3%, p < 0.01). The 5-year survival percentage (prostate cancer mortality) was improved for those patients diagnosed by PSA screening vs the non-screened group (100% vs 89.3%, p < 0.05). Conclusions: PSA screening has declined at HHS since the USPSTF recommendation against prostate cancer screening. Implementation of PSA screening in our healthcare system is expensive and leads to a high number of false positives. Despite this, the 5-year survival from prostate cancer is significantly higher when patients are diagnosed by PSA screening.
PSA doubling time (PSADT) and proximal PSA value predict metastasis-free survival (MFS) in men with biochemically recurrent prostate cancer (BRPC) after radical prostatectomy (RP).
Authors: Markowski Mark Christopher , Suzman Daniel , Chen Yongmei , Trock Bruce J. , Cullen Jennifer , Feng Zhaoyong , Antonarakis Emmanuel S. , Paller Channing Judith , Han Misop , Partin Alan W. , Eisenberger Mario A. 
Published: September 2018

5075 Background: We previously reported a relationship between PSADT and MFS in BRPC post RP (Pound 1999; Freedland 2007; Antonarakis 2012). In men with PSADT<12 months, who are at high risk of lethal PCa, we sought to identify a PSA cutpoint (proximal PSA; PP) that indicates the imminent emergence of metastasis (M+). In this report we combined Center for Prostate Disease Research and Johns Hopkins (CPDR/JHU) databases to investigate the association of the PP value on MFS in men with BRPC and PSADT <12 mos. Methods: In the CPDR/JHU RP database (31,296), 513 men with BCR (>0.2ng/ml) with PSADT <12 mos who received no adjuvant/salvage ADT/RT were prospectively followed until radiological evidence of M+ are included in this analysis. All patients were evaluated yearly with >1 PSA and scans at regular intervals until M+. Associations with MFS were compared using logrank test and Cox regression. The PP is the most recent value >6 months prior to M+/censor. Results: M+ occurred in 218 of 513 patients with BRPC (median follow up 9 years). Risk of M+ increased successively for PSADT 6.0-7.5, 4.5-6, 3.0-4.5, and <3.0 months, adjusted for pT stage and Gleason score. PP ≥10ng/ml significantly increased risk of M+ in pts with PSADT <12 mos, regardless of PSADT subgroup, hazard ratio=2.95, p<.0001. Median MFS was 4.0 years at PP >10ng/ml vs 20 years at PP <10ng/ml. Table 1 shows median MFS and 3, 5, and 7 year MFS rates in subgroups with PSADT <3 and 3.01-6 months representing the highest risk groups. Conclusions: In men with PSADT<12 months, PSADT subgroups <7.5 months and PP >10ng/ml are independent predictors of MFS, adjusted for pT stage and Gleason score. PP ≥10ng/ml further define risk of M+ in BRPC with PSADT<12 months. These data can assist physicians in patient counseling and clinical trial design. [Table: see text]
Survival impact of initial local therapy selection for men under 60 with high risk prostate cancer.
Authors: Kaiser Adeel , Bentzen Soren , Siddiqui Minhaj , Naslund Michael J , Kwok Young , Amin Pradip P. , Vujaskovic Zeljko , Mishra Mark Vikas , Badiyan Shahed Nicolas 
Published: September 2018

5082 Background: The impact of initial local therapy selection on survival for high risk prostate cancer (PCa) patients remains uncertain. We sought to assess this effect, while limiting competing causes of death, through the examination of a younger PCa patient cohort within the National Cancer Database. Methods: We evaluated the overall survival (OS) of men under 60 with high risk PCa receiving either radiation therapy (RT) or radical prostatectomy (RP). All men in this age group were treated between 2004 and 2013, harbored cN0M0 disease, and presented with Gleason Scores (GS) of 8 to 10. The RT group included patients who received external beam radiation (EBRT) alone or EBRT in combination with brachytherapy (BT). Overall survival and covariates were evaluated using multivariable Cox regression analysis. Results: A total of 16,944 patients met inclusion criteria of which 12,155 underwent RP and 4,789 received RT as initial therapy. 82.5% of RT patients received hormonal therapy, and the median dose was 77.4 Gy. In the RP group, 17.2% of patients received postoperative radiation, and 87% of these cases received a dose exceeding 64.80 Gy. The RP group had a higher proportion of cases with Charlson-Deyo comorbidity score > 0 (15.2% v. 11.2%, p < 0.000001). At a median follow-up of 50 months (0 - 131 months), RP was associated with improved OS in comparison to RT (hazard ratio = 0.52; 95% CI (0.47, 0.58); p < 0.000001). The estimated 8-year OS (±1 standard error of the estimate) was 85.1±0.7% and 74.9±0.7%, after RP and RT, respectively. This benefit remained present when adjusting for age, year of treatment, race, comorbidity score, Gleason score, T stage, hormonal therapy, chemotherapy, form of radiation, PSA, or insurance status. Conclusions: Compared to RT, initial treatment of men under 60 with high risk PCa with RP results in a large, statistically significant improvement in overall survival that remains consistent over time and remains significant in a multivariable model adjusting for known prognostic variables. These results are limited by the retrospective nature of the database analysis, and the lack of cancer specific survival information.
Survival outcomes of the NeoALTTO study: Updated results of a randomized multicenter phase III neoadjuvant trial.
Authors: Huober Jens Bodo , Holmes Eileen McCormick , Baselga Jose , De Azambuja Evandro , Untch Michael , Fumagalli Debora , Sarp Severine , Lang Istvan , Smith Ian E. , Boyle Frances M. , Xu Binghe , Lecocq Christophe , De La Pena Lorena , Jackisch Christian , Gelber Richard D. , Piccart-Gebhart Martine J. , Di Cosimo Serena 
Published: September 2018

512 Background: In the neoadjuvant NeoALTTO trial dual HER2 blockade with lapatinib (L) plus trastuzumab (T) combined with weekly paclitaxel significantly increased the pathologic complete response rate (pCR) compared with either anti-HER2 agent alone plus paclitaxel. At first analysis pts with pCR had a better event free survival (EFS) and overall survival (OS) after median follow-up of 3.84 yrs. Methods: 455 pts with operable HER2-positive breast cancer were randomized to receive either L (n=154) 1500mg/day, T 4mg/kg loading dose followed by 2mg/kg/wk (n=149) or L 1000mg/day plus T (n=152) for 6 weeks followed by the assigned anti-HER2 treatment combined with paclitaxel weekly x 12. Following surgery pts received 3 cycles fluorouracil, epirubicin and cyclophosphamide q 3 weeks. The assigned anti-HER2 treatment was continued for 34 weeks thereafter. Primary endpoint was pCR (ypT0/is), secondary endpoints were EFS and OS and the association between pCR and OS analyzed by landmark analysis 30 weeks after randomization. Median follow-up was 6.7 years. Results: 6-yrs EFS rate was 67%/ 67%/74% with L/T/TL, respectively (L vs T HR 0.98 [95% CI 0.64–1.51] p=0.93; TL vs T HR 0.81 [95% CI 0.52–1.26] p=0.35). In the hormone receptor negative group 6- yrs EFS rate was 61%/ 63%/74% for the 3 groups, respectively (L vs T HR 1.09 [95% CI 0.61–1.95] p=0.76; TL vs T HR 0.81 [95% CI 0.44–1.51] p=0.52). OS at 6 yrs was 82%/79%/85% for L, T and TL, respectively (L vs T: HR 0.85 [95% CI 0.49-1.46] p=0.56; TL vs T HR 0.72 [95% CI 0.41-1.27] p=0.26). In landmark analyses, pts with a pCR had significantly higher 6-yrs EFS (77% /65%) and OS (89% /77%) compared to those without pCR, both overall and for the hormone receptor negative cohort. Conclusions: The updated results of the NeoALTTO study confirm the sustained survival benefits for pts who achieve a pCR. EFS and OS after 6 yrs did not differ significantly between the 3 treatment groups. The combination of T and L showed numerically higher EFS compared to T, especially in the hormone-receptor negative group. Clinical trial information: NCT00553358. [Table: see text]
Chemotherapy (CT) for isolated locoregional recurrence (ILRR) of breast cancer in ER-positive (ER+) and ER-negative (ER-) cohorts: Final analysis of the CALOR trial.
Authors: Wapnir Irene , Price Karen N. , Anderson Stewart J. , Robidoux Andre , Martin Miguel , Nortier J. W.R. , Paterson Alexander H. G. , Rimawi Mothaffar F. , Lang Istvan , Baena Cañada José Manuel , Thurlimann Beat J. K. , Mamounas Eleftherios P. , Geyer Charles E. , Gelber Shari I. , Coates Alan S. , Gelber Richard D. , Rastogi Priya , Regan Meredith M. , Wolmark Norman , Aebi Stefan Paul 
Published: September 2018

513 Background: ILRR is associated with a high risk of developing breast cancer distant metastases and death. The CALOR trial (NCT00074152) investigated the effectiveness of CT following local therapy for ILRR. Previously reported results at 5-yrs median follow-up (MFU) showed significant benefit of CT for ER- ILRR, but further follow-up was required in ER+ ILRR. This report presents results at 8.8 yrs MFU within ER status cohorts. Methods: CALOR is an open-label, randomized trial for patients with completely excised ILRR after unilateral breast cancer. Eligible patients were randomized to CT (selected by the investigator; multidrug for at least 3 months recommended) or No-CT, and stratified by prior CT, hormone-receptor (ER, PR) status, and location of ILRR. Patients with ER and/or PR positive ILRR received adjuvant endocrine therapy. Radiation therapy was mandated for patients with microscopically involved margins, and anti-HER2 therapy was optional. Endpoints are disease-free survival (DFS), overall survival (OS) and breast cancer-free interval (BCFI). Results: From August 2003 to January 2010, 162 patients were enrolled: 104 ER+ and 58 ER-. The results at 8.8 years MFU in ER status cohorts are summarized in the Table (40 and 27 DFS events, respectively). The reduction in the hazard of an event associated with CT for the ER- ILRR cohort was sustained, but no benefit was observed for the ER+ cohort; interactions were significant for DFS and BCFI. The reduction in the hazard of an event seen in the ER- cohort was not apparent in ER+, with significant interactions for DFS and BCFI. Results for the 3 endpoints were consistent in multi-variable analyses adjusting for location of ILRR, prior chemotherapy, and interval from primary surgery. Conclusions: The final analysis of CALOR confirms that CT benefits patients with resected ER- ILRR. Long-term CALOR trial results do not support the use of CT for ER+ ILRR. Clinical trial information: NCT00074152. [Table: see text]
Breast conservation after neoadjuvant chemotherapy for triple-negative breast cancer: Surgical results from an international randomized trial (BrighTNess).
Authors: Golshan Mehra , Loibl Sibylle , Huober Jens Bodo , O'Shaughnessy Joyce , Rugo Hope S. , Wolmark Norman , McKee Mark D. , Maag David , Sullivan Danielle Marie , Giranda Vincent L. , Liu Xuan , Von Minckwitz Gunter , Geyer Charles E. , Sikov William M. , Untch Michael 
Published: September 2018

514 Background: Neoadjuvant systemic therapy (NST) increases the frequency of breast-conserving therapy (BCT) in stage II-III breast cancer, but there is little data on how often it converts patients (pts) from BCT-ineligible (BCT-I) to BCT-eligible (BCT-E) and on the impact of other factors on surgical choices. We collected surgical assessment and management data from an international randomized trial of NST in triple-negative breast cancer (TNBC). Methods: Women with operable TNBC were randomized to veliparib (V) with carboplatin (C) and paclitaxel (P), placebo with C and P or placebo with P followed by doxorubicin and cyclophosphamide. The surgeons assessed BCT candidacy by clinico-radiographic criteria before and after NST; surgical management was at surgeon and patient discretion. We assessed interactions between BCT eligibility pre- and post-NST, germline BRCA mutation ( gBRCA) status, continent of treatment and achievement of pathologic complete response(pCR) and percentage of pts who underwent BCT versus mastectomy. Results: Pre- and post-NST surgical assessments were available for 604 pts who underwent surgery. BCT rates are listed in the Table. The BCT rate was 68% among pts deemed BCT-E after NST. pCR rates were identical between BCT-E pts who chose BCT (55%) vs. mastectomy (53%). Of 141 pts deemed BCT-I at baseline, 75 (53%) converted to BCT-E but only 42 (56%) of these opted for BCT. pCR rates were 49% in BCT-E converts vs. 36% in those remained BCT-I. gBRCA pts (n = 84) were less likely to choose BCT even if they were BCT-E. Pts treated in North America (NA) were less likely to choose BCT (55% vs. 80% for Europe and Asia P<0.0001) even among non- gBRCA considered BCT-E post-NST (61% vs. 85% P<0.0001). Conclusions: This largest prospective analysis of the impact of NST in TNBC demonstrates a conversion rate from BCT-I to BCT-E of 53%. BCT rates were lower in pts with gBRCA; the much higher mastectomy rate among BCT-E pts in NA merits investigation. Clinical trial information: NCT02032277. [Table: see text]
Clinical outcomes in ER+ HER2-negative breast cancer (BC) where treatment decisions incorporated the 21-gene recurrence score (RS): Elderly (≥70 yrs) vs younger patients (Pts).
Authors: Stemmer Salomon M. , Steiner Mariana , Rizel Shulamith , Ben Baruch Noa , Soussan-Gutman Lior , Bareket-Samish Avital , Nisenbaum Bella , Isaacs Kevin , Fried Georgeta , Rosengarten Ora , Peretz Tamar , Svedman Christer , McCullough Debbie , Klang Shmuel , Zidan Jamal , Ryvo Larisa , Kaufman Bella , Shak Steven , Liebermann Nicky , Geffen David B 
Published: September 2018

543 Background: Elderly BC pts are generally undertreated, despite evidence suggesting that they may benefit from adjuvant chemotherapy (CT). We compared treatments/clinical outcomes in elderly vs younger Clalit Health Services (CHS) pts undergoing RS testing. Methods: This exploratory analysis of the CHS registry included BC pts with N0/N1mi/N1 disease who were RS-tested from 1/2006 (CHS approval of the test) through 12/2010 (N0) or 12/2011 (N1mi/N1). Medical records were reviewed to verify treatments/recurrences/survival. Results: The analysis included 458 elderly and 2052 younger pts, with a median (range) follow-up of 5.7 (0.9-9.6) and 6.1 (0.1-10.3) yrs, respectively. In the elderly/younger pts, median age was 73/58 yrs, 48%/52% had grade 2 tumors, median tumor size was 1.6/1.5 cm, 70%/72% were N0 and 30%/28% were N1mi/N1. RS distribution (<18, 18-30, ≥31) among elderly pts was 56%, 33%, and 11%, respectively, compared to 49%, 41%, and 10%, respectively, in younger pts. In pts with RS 18-30 and RS≥31, CT use was significantly lower in the elderly ( P<.001). Kaplan-Meier estimates for 5-yr distant recurrence and BC death risk are presented (Table). Conclusions: In elderly pts, the proportion of those with RS≥31 was very similar to younger pts; however, overall CT use was significantly lower. Within each RS group, there was no statistically significant difference in clinical outcomes between the age groups; though, numerically, in RS 18-30 pts, outcomes were worse in the elderly. In pts with RS<18, outcomes were excellent regardless of age and despite very low rates of CT use. [Table: see text]
LION: Lymphadenectomy in ovarian neoplasms—A prospective randomized AGO study group led gynecologic cancer intergroup trial.
Authors: Harter Philipp , Sehouli Jalid , Lorusso Domenica , Reuss Alexander , Vergote Ignace , Marth Christian , Kim Jae Weon , Raspagliesi Francesco , Lampe Boern , Landoni Fabio , Meier Werner , Cibula David , Mustea Alexander , Mahner Sven , Runnebaum Ingo B. , Schmalfeldt Barbara , Burges Alexander , Kimmig Rainer , Wagner Uwe A. G. , Du Bois Andreas 
Published: September 2018

5500 Background: So far, there is no level-1 evidence regarding the role of systematic pelvic and para-aortic lymphadenectomy (LNE) in patients with advanced ovarian cancer (AOC) with macroscopic complete resection und clinically negative lymph nodes (LN). Therefore, surgical management regarding LNE worldwide is very heterogeneous. Methods: Prospective randomized trial including patients with newly diagnosed AOC FIGO IIB-IV with macroscopic complete resection and pre- and intra-operatively clinical negative LN were randomized intra-operatively to LNE versus no-LNE. All centers had to qualify regarding surgical skills before participation in this trial. The primary endpoint was overall survival. Results: 647 patients were randomized between 12/08 and 1/12 to LNE (n=323) or no-LNE (n=324). The median number of removed LN in patients randomized to LNE was 57 (pelvic 35 and para-aortic22). Post-op platinum-taxane based chemotherapy was applied in 85% of the patients in the no-LNE arm and 80% in the LNE arm. Microscopic metastases were diagnosed in 56% of the pts in the LNE arm. Median OS in the no-LNE arm was 69 months and 66 months in the LNE arm (HR 1.06, 95%CI 0.83-1.34, p=0.65) and the median PFS was 26 months in both arms (HR 1.11, 95%CI 0.92-1.34 p=0.30). Surgery in the LNE arm was 64 minutes longer (means: 352 vs 288 min), resulted in a higher median blood loss (650 vs 500 ml), and a higher transfusion rate (67% vs 59%). Furthermore, serious post-operative complications occurred more frequently in the LNE arm (e.g. rate of re-laparotomies 12.1% vs 5.9% [p=0.006], hospital re-admittance rate 8.0% vs 3.1% [p=0.006] and deaths within 60 days after surgery 3.1 vs 0.9% [p=0.049]). Conclusions: Systematic pelvic and para-aortic LNE in patients with AOC with both intra-abdominal complete resection and clinically negative LN neither improve overall nor progression-free survival despite detecting (and removing) sub-clinical retroperitoneal lymph node metastases in 56% of the patients. Our data indicate that systematic LNE of clinical negative LN in patients with AOC and complete resection should be omitted to reduce post-operative morbidity and mortality. Clinical trial information: NCT00712218.