bluuebunny/crossref_metadata_2025_split huggingface dataset:
A national survey of radiation oncologists and urologists on active surveillance for low-risk prostate cancer.
Authors: Kim Simon P. , Karnes R. Jeffrey , Nguyen Paul Linh , Leibovich Bradley C. , Ziegenfuss Jeanette Y. , Thompson R. Houston , Boorjian Stephen A. , Han Leona C. , Costello Brian Addis , Tilburt Jon C. 
Published: March 2020

4657 Background: While active surveillance (AS) is well recognized as an acceptable treatment strategy for low-risk prostate cancer (PC), the extent to which radiation oncologists and urologists perceive AS as effective and routinely recommend it to patients is unknown. Therefore, we sought to assess the attitudes and treatment recommendations for low-risk PC from a national survey of PC specialists. Methods: A mail survey was sent to a population-based sample of 1,439 physicians in the U.S. from late 2011 and early 2012. Physicians were queried about their attitudes regarding AS and treatment recommendations for patients diagnosed with low-risk PC (PSA<10 ng/dl; T1c; Gleason 6 in one of twelve cores). Pearson Chi-square and multivariate logistic regression were used to test for differences in attitudes and treatment recommendations by physician demographics, compensation structure, primary place of employment, and specialty. Results: Overall, 321 radiation oncologists and 322 urologists completed the survey for a 45% response rate. Most physicians reported that AS is effective for low-risk PC (71%) and stated that they were comfortable routinely recommending AS (67%). Urologists were more likely to agree that AS is effective (77% vs. 67%; p=0.005) and were comfortable recommending AS (74% vs. 61%; p=0.001) compared with radiation oncologists. Most physicians recommended radical prostatectomy (47%) or radiation therapy (32%), but fewer endorsed AS (21%) for low-risk disease. After adjusting for physician covariates, radiation oncologists were more likely to recommend radiation therapy (OR: 10.97; p<0.001), while urologists were more likely to recommend surgery (OR: 4.69; p<0.001) and AS (OR: 2.18; p=0.001) for low-risk PC. Conclusions: Although AS is widely viewed as effective by both radiation oncologists and urologists, most urologists continue to recommend surgery, while most radiation oncologists recommend radiation therapy. Our results may explain in part the relatively low contemporary use of AS in the U.S.
Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase I trial in metastatic castration-resistant prostate cancer (mCRPC) previously treated with a taxane.
Authors: Mega Anthony E. , Petrylak Daniel Peter , Kantoff Philip , Stephenson Joe , Vogelzang Nicholas J. , Dreicer Robert , Shore Neal D. , Stambler Nancy , Carpenito Jennifer , D'Ambrosio Paul , Israel Robert Joseph 
Published: March 2020

4662 Background: The abundant expression of prostate specific membrane antigen (PSMA) type II transmembrane glycoprotein on prostate cancer cells provides a rationale for antibody therapy. PSMA ADC, a fully humanized antibody to PSMA linked to the potent antitubulin agent monomethyl auristatin E (MMAE), binds PSMA and is internalized within the prostate cancer cell where cleavage by lysosomal enzymes and releases free MMAE, causing cell cycle arrest and apoptosis. We report results from an ongoing phase 1 dose escalation study of PSMA ADC in subjects with taxane-refractory mCRPC. Methods: Eligibility requirements include progressive mCRPC following taxane-containing chemotherapy and ECOG status of 0 or 1. PSMA ADC was administered by IV infusion Q3W for up to 4 cycles. Adverse events, pharmacokinetics (PK), PSA, circulating tumor cells, clinical disease progression and immunogenic response to PSMA ADC were assessed. Serum PSMA ADC and total antibody were measured by ELISA, and free MMAE was measured by LC/MS/MS.The dosing cohorts range from 0.4 mg/kg to 2.8 mg/kg, with dose escalation continuing. Results: 40 subjects have been dosed in nine dose levels (0.4, 0.7, 1.1, 1.6, 1.8, 2.0, 2.2, 2.5, 2.8 mg/kg). To date, PSMA ADC has been well tolerated with the most commonly seen adverse events being anorexia and nausea, and the most common laboratory abnormalities being reversible hematologic parameters and liver function tests. Antitumor activity has been manifested as reductions either in PSA or circulating tumor cells in the higher dose cohorts. Exposure to PSMA ADC increased with dose and was ~1,000-fold greater than MMAE exposure. Similar PK metrics were observed after the first and third doses. Dosing at the 2.8 mg/kg cohort is continuing and an MTD has not yet been reached. Conclusions: PSMA ADC is generally well tolerated in subjects with mCRPC, previously treated with taxane in doses up to 2.8 mg/kg. Antitumor activity at higher dose levels has been observed. The MTD has not yet been reached and enrollment is ongoing at higher dose levels.
Phase I clinical trial of galeterone (TOK-001), a multifunctional antiandrogen and CYP17 inhibitor in castration resistant prostate cancer (CRPC).
Authors: Montgomery Robert B. , Eisenberger Mario A. , Rettig Matthew , Chu Franklin , Pili Roberto , Stephenson Joe , Vogelzang Nicholas J. , Morrison Jodie , Taplin Mary-Ellen 
Published: March 2020

4665 Background: Galeterone is an oral steroid analog that suppresses prostate cancer growth by inhibiting CYP17, blocking androgen receptor and reducing androgen receptor levels. Methods: Open label, multicenter dose-finding study assessing the safety, pharmacokinetics and clinical effect of escalating doses of galeterone in chemotherapy naïve CRPC patients (pts). Pts were enrolled in cohorts from 650-2,600mg of galeterone daily for 12 wks. Study also explored effects of food supplement and scheduling. Pts remained on study until disease progression or dose limiting toxicity. Results: Pt characteristics included median age 69 (47-92), median PSA 24 (6-200), and 46.9% with metastases. 36 of 49 pts completed 12 wks of study with early discontinuation for toxicity (6), progression (5), or withdrawal of consent (2). Maximal tolerated dose was not reached. The frequency of AEs was 58% grade 1, 30% grade 2, 8% grade 3 and 1% grade 4. Transient LFT elevations were seen in 15 men (5 with suspected or confirmed Gilberts). There was no trend for increasing toxicity with dose escalation and no PK difference in Gilberts pts. 9 SAEs were reported with one considered related to galeterone (rhabdomyolysis with acute renal failure in the context of high dose statin use). Overall 11/49 pts (22%) demonstrated >50% PSA decline and an additional 13/49 (26%) had 30-50% declines. Partial response by RECIST was seen in 2 pts. Consistent with lyase inhibition, increased corticosteroids and suppressed androgens were seen with dose escalation. Analysis of limited plasma collected 4 - 30 hours after dosing showed high interpatient variability with no consistent relationship to dose or time after dosing. Conclusions: Galeterone was well tolerated in CRPC pts and demonstrated clinical activity. Galeterone is being reformulated with additional PK and phase II trials planned. [Table: see text]
The impact of prior therapy with ketoconazole (keto) on clinical outcomes after subsequent docetaxel treatment in metastatic castration-resistant prostate cancer (mCRPC) patients: Results from a randomized phase III trial (CALGB 90401).
Authors: Small Eric Jay , Halabi Susan , Carducci Michael Anthony , Ryan Charles J. , George Daniel J. , Mahoney John Francis , Stadler Walter Michael , Morris Michael J. , Kantoff Philip , Monk J. P. , Kelly William Kevin 
Published: March 2020

4667 Background: Small retrospective reviews have suggested the possibility of a decreased benefit of docetaxel in mCRPC patients (pts) previously treated with abiraterone acetate, a novel androgen synthesis inhibitor (ASI). CALGB 90401 was an intergroup (CALGB, ECOG) randomized phase 3 trial in which 1050 mCRPC pts were treated with docetaxel, which offered the opportunity to evaluate the effect of prior treatment with keto, an earlier generation ASI, on clinical outcomes following docetaxel treatment in mCRPC pts. Methods: Data from 1,050 men randomized on CALGB 90401 to treatment with docetaxel and prednisone with either bevacizumab or placebo were used. Pts were chemotherapy naïve, had evidence of progressive mCRPC, an ECOG performance status ≤ 2, and adequate bone marrow, hepatic and renal function. Randomization was stratified by age, prior history of a thromboembolic event, and 24-month predicted survival using the CALGB nomogram. The effect of prior keto use on overall survival (OS), progression-free survival (PFS), PSA decline, and objective response rate (RR) was estimated using proportional hazards and logistic regression models. Results: 277/1050 pts (26%) had received prior keto. Baseline characteristics including the 3 stratification factors, race, performance status, measurable disease, and baseline alkaline phosphatase and Hgb were balanced between prior keto treated pts and keto untreated pts. LDH and PSA were higher in the keto treated patients (211 vs. 201, p = 0.01; and 121 vs. 73, p < .0001; respectively.) There were no statistically significant differences in keto vs. non-keto treated patients with regards to OS (21.1 vs. 22.3 m, p = 0.643); PFS (8.1 vs. 8.6m p = 0.394 ); >50% decline in PSA (61% vs. 66% p=.112); or objective response (39% vs. 43% p = 0.34). Conclusions: As measured by OS, PFS, PSA and RR, prior treatment with the ASI ketoconazole has no impact on the subsequent clinical impact of docetaxel in mCRPC pts.
Incidence-based analysis of lethal prostate cancer in Swedish counties with high versus low incidence of prostate cancer in nationwide, population-based registries.
Authors: Stattin Pär , Holmström Benny , Robinson David , Vickers Andrew J. , Lilja Hans , Hugosson Jonas , Jonsson Håkan 
Published: March 2020

4668 Background: Current data from randomized trials differ in the ratio of benefit to harms from screening for prostate cancer (PC) using prostate specific antigen (PSA) testing and it is further unclear if decreases in PC mortality in the US can be attributed to introduction of screening or to changes in treatment. The aim of this study was to investigate if rapidly increased incidence of PC diagnosis due to early and rapidly increased rate of PSA testing, is associated with decreased incidence of lethal PC. Methods: In this incidence-based study using highly representative data from nation-wide population-based registries we analysed the incidence of lethal prostate cancer in eight Swedish counties with the most rapid and largest increased incidence of PC diagnosis (high incidence counties) from 1995 through 2002, and six counties with the smallest increased PC incidence (low incidence counties). We analysed the rate ratio (RR) in high vs. low incidence counties of cases with metastatic PC at diagnosis, (positive bone scan or PSA above 100 ng/ml), PC-specific mortality, and excess mortality (death among PC cases regardless of cause). Participants were men aged 50-74 years during 2000 to 2009 in the high versus low incidence counties contributing 4,528,134 versus 2,471,373 person-years at risk, respectively. There were 33,780 incident PC diagnoses and 1,577 PC deaths in high incidence counties and 16,377 PC cases and 985 PC deaths in low incidence counties. Results: In high vs. low incidence counties, RR of metastatic PC was 0.85 (95% confidence interval [CI] = 0.79 to 0.92), RR of PC-specific mortality was 0.87 (95% CI = 0.81 to 0.95) and RR of excess mortality in men with PC was 0.75 (95 %CI = 0.66 to 0.86). Conclusions: Our study provides data on a population-level indicating a decreased incidence of lethal PC in areas with rapid and large increase in incident PC diagnosis due to increased rates of PSA testing, early diagnosis, and treatment with curative intent.
Impact of adjuvant therapy in lymph-node positive vulvar cancer: The AGO CARE 1 study.
Authors: Mahner Sven , Jueckstock Julia Kathrin , Hilpert Felix , Lubbe Dirk , Harter Philipp , De Gregorio Nikolaus , Iborra Severine , Chen Frank , Stoenescu Adela , Hillemanns Peter , Fuerst Sophie , Strauss Hans-Georg , Baumann Klaus H. , Thiel Falk , Mustea Alexander , Meier Werner , Du Bois Andreas , Wimberger Pauline , Griebel Lis-Femke , Woelber Linn Lena ,   AGO-CaRE-1 Investigators
Published: March 2020

5007 Background: While the majority of patients with vulvar cancer can be cured by surgery alone, women with lymph-node metastases often show unfavorable outcome. Improved treatment strategies are therefore strongly needed. Methods: Patients with primary squamous-cell vulvar cancer treated at 29 gynecologic cancer centers in Germany between 1998 and 2008 were included in a centralized database and analyzed retrospectively. Results: A total of 1,637 patients were documented with a median follow-up of 121 months. UICC-Stage distribution was 597 (36.5 %) T1, 816 (49.8 %) T2, 160 (9.8 %) T3 and 31 (1.9 %) T4, 33 (2.0 %) were missing. 491 patients had lymph-node metastasis to the groins (N+). 214 N+ patients (43.6 %) developed recurrent disease within a median of 21.4 months. 190 N+ patients (38.7%) died, median overall survival (OS) was 43.4 months, compared to 212 months for node-negative patients. An increasing number of metastatic lymph-nodes was associated with shorter OS: 169 (34.4%) patients had 1, 101 (20.6%) patients 2, 62 (12.6%) patients 3 and 86 (17.5%) patients >3 positive lymph-nodes, with a corresponding OS of 22.4, 17.2, 18.4 and 10.2 months, respectively (for 73 patients the number of nodes was not available). 240 N+ patients were treated with adjuvant radiotherapy (85.8%) or radiochemotherapy (14.2%). Median OS in these patients was significantly longer (66.9 months) compared to N+ patients without adjuvant treatment (35.7 months), the corresponding hazard ratio (HR) was 0.72 (95 % CI: 0.53 - 0.97 p = 0.029). This impact on OS remained consistent in multivariate analysis adjusted for age, ECOG, stage, grading, invasion depth and number of positive nodes (HR 0.68; 95% CI: 0.49 - 0.94 p = 0.020) and was observed irrespective of the number of affected nodes. Conclusions: To this day, this is the largest multicenter study on vulvar cancer. Our findings strongly suggest that the unfavorable prognosis of patients with node positive vulvar cancer can be improved by adjuvant therapy irrespective of the number of affected nodes. As adjuvant radiochemotherapy was shown to be superior to radiotherapy alone in many other squamous cell carcinomas, we are preparing a prospective phase III trial in node-positive vulvar cancer (AGO-CaRE 2 trial).
Effect of osteoporosis in postmenopausal breast cancer patients randomized to adjuvant exemestane or anastrozole: NCIC CTG MA.27.
Authors: Shepherd Lois E. , Chapman Judy-Anne W. , Ali Suhail M. , Zhu Liting , Leitzel Kim , Goss Paul Edward , Lipton Allan 
Published: March 2020

501 Background: NCIC CTG MA.27 compared adjuvant steroidal [exemestane (E)] and non-steroidal [anastrozole (A)] aromatase inhibitors (AIs) and showed neither to be superior in breast cancer outcomes. AIs are known to increase the risk of osteoporosis. We examined the effects of baseline or subsequent self reported osteoporosis on disease outcomes. Methods: MA.27 enrolled 7,576 women. Event free survival (EFS) was the primary endpoint. Distant disease-free-survival (DDFS) was a secondary outcome. MA.27 permitted bisphosphonates to prevent or treat osteopenia or osteoporosis unless prohibited by enrollment to one of two cohorts in a bone substudy. Osteoporosis was considered present for this analysis if reported at baseline or prior to relapse or breast cancer death. Multivariate stratified Cox regression was used to examine the effects of trial therapy, osteoporosis, baseline patient and tumour characteristics on EFS; DDFS; bone only relapse; bone concurrent with other relapse; and non-bone recurrence. Bone marrow recurrence (N=8) was excluded. Results: Osteoporosis was reported at baseline by 654 of 7576 (8.6%) women, and prior to relapse by an additional 661 women. EFS events occurred in 693/7576 (9.15%). Osteoporosis was significantly associated with better EFS [HR 0.81 (95% CI 0.66-0.99), p=0.04] with no difference in multivariate HR of E vs A: 1.02, 95% CI 0.88-1.19, p=0.77. Women experienced 313 (4.1%) DDFS events. Osteoporosis was associated with better DDFS [HR 0.71 (95% CI 0.51-0.98), p=0.04], adjusted HR of E to A: 0.94 (95% CI of 0.75-1.17), p=0.56. Both EFS and DDFS interactions of osteoporosis with trial therapy were not significant (p>0.05). Osteoporosis was not significantly associated with the site of relapse. Conclusions: Osteoporosis had a significant prognostic association with improved EFS and DDFS in women treated with AIs. We plan to investigate the use of bisphosphonates, raloxifene treatment prior to randomization, and markers of bone resorption with outcome.
A phase II, open-label, multicenter study of IMC-1121B (ramucirumab; RAM) monotherapy in the treatment of persistent or recurrent epithelial ovarian (EOC), fallopian tube (FTC), or primary peritoneal (PPC) carcinoma (CP12-0711/NCT00721162).
Authors: Penson Richard T. , Moore Kathleen N. , Fleming Gini F. , Braly Patricia S. , Schimp Veronica L. , Nguyen Hoa , Matulonis Ursula , Banerjee Susana N. , Haluska Paul , Gore Martin Eric , Bodurka Diane C. , Morozov Alexei , Xu Yihuan , Rutstein Mark D. , Schwartz Jonathan D. , McGuire William P. 
Published: March 2020

5012 Background: VEGF receptor-mediated-signaling contributes to ovarian cancer pathogenesis. Elevated VEGF expression and serum levels are associated with poor clinical outcomes. We investigated RAM, a fully human VEGFR-2 antagonist antibody, in patients (pts) with persistent or recurrent EOC/FTC/PPC. Methods: Adult women with EOC/FTC/PPC who had completed ≥1 platinum (P)-based chemotherapeutic (ct) regimen and had a P-free interval (PFI) of <12 months (m), progression on, or persistent disease after P-based therapy were eligible. Any number of prior ct regimens was allowed. ECOG PS 0-1 and adequate organ function were required. Pts received 8 mg/kg RAM IV every 2 weeks. Primary endpoints were progression-free survival at 6m (PFS-6) and confirmed objective response rate (ORR) by RECIST 1.0. Results: 60 pts were treated; 1 remains on study as of Dec 2011. Median age was 62 years (range 27-80). Median number of prior regimens was 3 (range 1– 14). 51 pts (85%) received ≥ 2 prior regimens; 25 pts (42%) received >3 prior regimens. 45 pts (75%) were P resistant or refractory, with 65% (39 pts) serous tumors. PFS-6: 34.2% (95% CI: 21.7% – 47%). Best overall response: 3 PR (5%), 34 SD (57%), 20 PD (33%) and 3 not evaluable (5%). Median duration of PR: 5.6m (3.7, 5.6, 17.5); median PFS: 3.5m (95% CI: 2.3 – 5.3). Median OS: 11.1m (95% CI: 8.3 – 17.0). No unexpected toxicities were observed. Grade (G) 3 adverse events (AEs) observed in >5% of pts were: headache (10%) and fatigue (8%). No G4 AEs were observed in >5% of pts. 5 deaths occurred on RAM or within 30 days of discontinuation; 4 due to PD, and 1 due to intestinal perforation. 1 G4 bowel perforation and one G4 colo-vaginal fistula were noted. All 3 cases of perforation/fistula occurred in the setting of progressive, large-volume disease. Correlative biomarker studies are ongoing to identify patients most likely to benefit. Conclusions: Ramucirumab was reasonably tolerated and demonstrated single-agent activity in persistent or recurrent ovarian carcinoma, with approximately one-third of patients progression free at 6 months.
Phase II trial of irinotecan plus bevacizumab for heavily pretreated recurrent ovarian cancer.
Authors: Jain Salvia Sanjay , Makeyev Yan G. , Muggia Franco , Speyer James L. , Curtin John Patrick , Blank Stephanie V. , Boyd Leslie R. , Pothuri Bhavana , Fishman David , Li Xiaochun , Goldberg Judith D. , Tiersten Amy 
Published: March 2020

5016 Background: Irinotecan and bevacizumab have single agent activity in platinum sensitive (PSen) and resistant (PRes) ovarian cancer patients (pts). We sought to evaluate the efficacy and toxicity of irinotecan plus bevacizumab in these pts. The trial was designed to evaluate whether the progression free survival (PFS) at 6 months is at least 40% and with secondary objectives of estimating response rate (RR), duration of response (DoR), time to progression and toxicity. Methods: No limitation on number of prior regimens was placed, and prior use of study drugs was allowed. Irinotecan 250mg/m2 and bevacizumab 15mg/kg every 3 weeks were given. Due to treatment-related grade 3 toxicity (diarrhea and neutropenia) experienced by the first 5 pts on the study, the dose of irinotecan was amended to 175mg/m2. Results: 20 pts with recurrent ovarian cancer [PSen 5, PRes 15] of a planned 35 have been recruited thus far. Median age is 59 (45-78). Median number of prior regimens is 5 (3-12) with 9 pts demonstrating progressive disease (PD) on prior topotecan-containing regimens and 7 pts exhibiting PD on prior bevacizumab-containing regimens. 4 pts discontinued treatment before 2 cycles (2 for protocol defined toxicity, 2 by patient/physician choice). Partial response (PR) was observed in 2 PSen pts and 1 PRes pt, while stable disease (SD)was seen in 9 (2 PSen, 7 PRes) out of the 15 pts assessable for response at this time. 3 pts demonstrated PD after 2 cycles of treatment. 12 of 13 pts with PR or SD by RECIST also had response by CA125 criteria. Median DoR thus far (SD plus PR) is 18 weeks (4-37). 6 pts have ongoing response (4-18 weeks). Of 19 pts that received > 2 cycles, 3 had grade 3 diarrhea (2 before protocol amendment and 1 after). 2 pts had grade 3/4 neutropenia (1 before and 1 after protocol amendment). Median PFS is 9.6 months (mts). Median overall survival is 15.5 mts. PFS rate at 6 mts is 61% with 95% confidence interval: (40%, 92%). Conclusions: Results of the trial to date suggest the hypothesis that the PFS at 6 mts is less than 40% can be rejected. Activity of this regimen is encouraging given the heavily pretreated nature of the pts. Dose-limiting diarrhea and neutropenia required protocol amendment. We continue to accrue study subjects at the amended dosing.