bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating free DNA and circulating tumor cells as new serum biomarkers in advanced ovarian cancer.
Authors: Martinez Garcia Jeronimo , Soto Asuncion , Sanchez-Henarejos Pilar , Puertes Boix Ana , Rodriguez Edith , Guirao Maran Marta , Jimenez-Lucas MDolores , Cuellar Miler , Cano Alicia , Alonso Romero Jose Luis , Ruiz Merino Guadalupe , Collados David , Marin Miguel , Ros Silver , Garcia Hernandez Maria Del Rosario , Salgado Rosario 
Published: September 2018

5566 Background: Circulating free DNA (cfDNA) and circulating tumor cells (CTC) are new biomarkers for malignant tumors. Its role on ovarian epithelial cancer (OEC) is not yet well stablished. We analyze its role on advanced OEC compared with CA125 and HE4. Methods: Multicentric prospective observational study from November 2013 until February 2017, with OEC patients group (OECG), benign ovarian tumors group (BENIGNG) and health subjects control group (HEALTHG). CTCs were analysed by the CellSearch method and cfDNA by ALU-sequences-based quantitative PCR using two primers (115 and 247 bp); cfDNA integrity was calculated by ALU247/ALU115 ratio. Samples were obtained before treatment (M0), after primary peritoneal surgery (M1), after one cycle of chemotherapy (M2), before (M3) and after interval surgery (M4). This study was approved on May 2013 by the corresponding Central Research Independent Ethics Committee. Results: We analyized 102 subjects from all 3 groups (81 OECG, 14 BENIGNG y 7 HEALTHG); 68% were high grade serous subtype; most frequent staging was IIIC (58%). Within the follow-up (FU) period (average 14 months: min 0, max. 35) 36% relapses and 23% deaths were reported. CTCs were positive on 23% of OECG. In HEALTHG no positive were seen and only 1/14 in the BENIGNG group. Monitoring of cfDNA at the treatment points shows significant differences between M0 and M4 (p = 0.02). No differences were seen in the other determinations. cfDNA-ALU115 was 1.40178 ng / mcL (95% CI 1.18066-1.62290) in the OECG, 0.66383 (95% CI 0.44832-0.87935) in BENIGNG and 0.59923 in HEALTHG ( 95% CI, 0.14449-1.05397). The difference was significant between OECG and BENIGNG (P = 0.017) and near the significance between OECG and HEALTHG (p = 0.69). cfDNA integrity in OECG and HEALTHG was significantly different (P = .012). The area under the curve of Ca125, HE4, CTC, cfDNA and CFDNA integrity was 0.490, 0.526, 0.621, 0.587 and 0.450 respectively. New generation sequencing of circulating TP53 is ongoing. Conclusions: CTC and cfDNA are new biomarkers that might have an important role in the diagnosis and monitoring of OEC.
A phase Ib/II trial of lenvatinib (LEN) plus pembrolizumab (Pembro) in patients (Pts) with endometrial carcinoma.
Authors: Makker Vicky , Rasco Drew W. , Dutcus Corina E , Stepan Daniel E. , Li Di , Schmidt Emmett V. , Shumaker Robert Charles , Taylor Matthew H. 
Published: September 2018

5598 Background: LEN is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1−3, fibroblast growth factor receptor 1−4, platelet-derived growth factor receptor α, RET, and KIT. Pembro, an antibody targeting programmed cell death protein 1 (PD-1), prevents T cell deactivation. In addition to its antiangiogenic effects, LEN may act in part by preventing VEGF-mediated immune suppression, suggesting combination with pembro could improve its activity. We report results in pts with endometrial carcinoma from a phase Ib/II trial of LEN + pembro. Methods: In this multicenter, open-label study, pts had confirmed metastatic endometrial cancer that progressed after approved therapy, measurable disease, and ECOG performance status ≤ 1. Pts received oral LEN 20 mg/day plus pembro 200 mg intravenously every 3 weeks. Tumor assessments were by the investigator. The primary phase II endpoint was objective response rate (ORR) based on immune-related RECIST (irRECIST). Secondary endpoints included progression-free survival (PFS), disease-control rate (DCR; complete response [CR] + partial response [PR] + stable disease [SD]), clinical-benefit rate (CBR; CR + PR + durable SD), and duration of response (DOR), all by irRECIST, and safety. Results: 23 Pts enrolled (phase II: 21; phase Ib: 2); median age was 64 years (range: 51−80); 87% were white; and all had ≥ 1 prior anticancer therapy. Confirmed ORR was 48% (all PR). Median PFS and DOR were not estimable (NE; see table). All pts had a treatment-emergent adverse event (TEAE). The most common TEAEs were hypertension, fatigue, arthralgia, diarrhea, and nausea. Toxicities were manageable with dose interruption and/or modification and no new safety signals were found. Updated data will be presented. Conclusions: Promising efficacy was observed in pts receiving LEN + pembro. In addition, toxicities were generally expected and manageable with dose modification. These results warrant further study of LEN + pembro in pts with endometrial carcinoma. Clinical trial information: NCT02501096. [Table: see text]
What drives overtreatment? Surgeon and radiation oncologist views on omission of adjuvant radiotherapy for elderly women with early stage breast cancer.
Authors: Shumway Dean Alden , Griffith Kent A. , Sabel Michael S. , Jones Rochelle , Hawley Sarah T. , Jeruss Jacqueline Sara , Jagsi Reshma 
Published: September 2018

562 Background: Although trials have shown no survival advantage and only a modest improvement in local control from adjuvant radiotherapy after lumpectomy in older women with stage I, ER+ breast cancer, radiotherapy is commonly administered, raising concerns about overtreatment. Therefore, we sought to evaluate physician attitudes, knowledge, communication, and recommendations in this scenario. Methods: We mailed a survey to a national sample of 713 radiation oncologists and 879 surgeons between June to October 2015. Of these, 913 responded (57%). We assessed physicians’ attitudes, knowledge of pertinent risk information, and responses to clinical scenarios. Results: In patients age > = 70 with stage I, ER+ breast cancer treated with lumpectomy and endocrine therapy, omission of radiotherapy was felt to be unreasonable by 40% of surgeons and 20% of radiation oncologists (p < 0.001). Many surgeons (29%) and radiation oncologists (10%) erroneously associated radiotherapy in older women with improvement in survival. Similarly, 32% of surgeons and 19% of radiation oncologists tended to substantially overestimate the risk of locoregional recurrence in older women with omission of RT. In a scenario with an 81-year-old with multiple comorbidities, 31% of surgeons and 35% of radiation oncologists would still recommend radiotherapy. On multivariable analysis, erroneous attribution of a survival benefit to radiotherapy (OR 6.2; 95% CI 3.9-9.8) and overestimation of remaining life expectancy (OR 6.5; CI 4.2-9.9) were strongly associated with the opinion that radiotherapy omission is unreasonable. Conclusions: Many radiation oncologists and surgeons continue to consider omission of radiotherapy as substandard therapy. A sizeable proportion of surgeons overestimate radiotherapy’s benefits and consider omission of radiotherapy to be an unreasonable departure from the standard of care, suggesting that surgeon involvement in decisions about radiotherapy omission may be a key factor in reducing overuse of aggressive care in this setting.
Locoregional surgery of the primary tumor in stage IV breast cancer patients.
Authors: Wang Ying , Yu Yunfang , Chen Kai , Fu Tuping , Yao Herui 
Published: September 2018

566 Background: Existing guidelines lack clear recommendations for the role of locoregional treatment for the primary tumor in women with stage IV breast cancer. We aimed to compare the effectiveness of locoregional surgery with no surgery of the primary tumour in stage IV breast cancer patients. Methods: Eligible studies were randomized clinical trials (RCTs) that investigated the effect of locoregional surgery versus no surgery of the primary tumour in stage IV breast cancer patients. The primary outcome was overall survival (OS), measured as hazard ratios (HRs). Secondly outcomes included 2-year and 3-year OS, expressed as odds ratios (ORs). Meta-analyses and trial sequential analysis (TSA) were conducted. Quality was evaluated using the GRADE. Results: Data were included from four RCTs involving 767 participants, including 377 who underwent locoregional surgery and 390 who with no surgery. The median follow-up was 28.6 months (95% confidence interval (CI) 24.1 to 33.9). In a meta-analysis of these trials, the low-quality evidence indicated that locoregional surgery versus no surgery did not significantly affect OS (HR = 0.87, 95% CI 0.59 to 1.29, P = 0.490), 2-year OS (OR = 1.23, 0.66 to 2.30, P = 0.510), or 3-year OS (OR = 1.08, 0.94 to 1.25, P = 0.263). TSA showed that more trials were needed before reliable conclusions could be drawn regarding in both 2-year and 3-year OS. Across the subgroup analysis of OS, we found the moderate-quality evidence that locoregional surgery followed by chemotherapy versus chemotherapy alone resulted into a significantly improved survival (HR = 0.65, 95% CI 0.49–0.87, P = 0.004); but no statistically significant difference was identified in term of response to chemotherapy with or without locoregional surgery (HR = 1.06, 95% CI 0.83–1.36, P = 0.632). Conclusions: The current evidence suggests that locoregional surgery followed by chemotherapy, compared with chemotherapy alone, was beneficial for prolonging OS in patients with stage IV breast cancer, but surgery did not impact OS among patients who have responded to chemotherapy.
Adjuvant or neoadjuvant chemotherapy in early stage triple negative breast cancer (TNBC) comparison of outcomes in both BRCA positive and BRCA negative patients.
Authors: Clifton Katherine , Gutierrez Barrera Angelica , Ma Junsheng , Bassett Roland L. , Litton Jennifer Keating , Arun Banu 
Published: September 2018

576 Background: NSABP Protocol B-18 was a randomized trial which found no statistically significant difference in overall survival (OS) in patients (pts) receiving neoadjuvant (NAC) or adjuvant chemotherapy (AC), however outcome was not analyzed by breast cancer subtypes. Subsequent retrospective studies in TNBC reported conflicting results with an initial study showing a significant OS benefit with AC and later studies showing a trend toward improved survival with NAC. Furthermore, studies have not included a significant number of pts with BRCA mutations. This study aims to analyze outcomes of AC versus NAC in pts with early stage TNBC with and without BRCA germline mutations. Methods: Pts with stage I or II TNBC who had BRCA testing were identified from a prospective cohort study of 4027 pts at MD Anderson Cancer Center. Clinical, demographic, genetic test results, chemotherapy, recurrence, survival data were collected. OS and disease free survival (DFS) were estimated using the Kaplan-Meier method, and log-rank tests were used to compare groups. Results: 305 pts with stage I and II TNBC who met eligibility criteria were included in the analysis. Pts who received both NAC and AC or no chemotherapy were excluded. 181 received AC (59.3%) and 124 received NAC (40.7%). The majority of the pts were less than 50 years old (236, 77.4%) and white (194, 63.8%). 134 were BRCA positive (44.1%) and 170 were BRCA negative (55.9%). The majority of the pts received an anthracycline and taxane regimen (223, 73.1%). There was no significant association between OS or DFS and treatment with NAC versus AC in the overall cohort. Furthermore, there were no significant differences between pt subgroups (NAC BRCA positive, NAC BRCA negative, AC BRCA positive, and AC BRCA negative) with respect to either OS or DFS. Conclusions: NAC versus AC with standard anthracycline and taxane containing regimens results in similar DFS and OS survival amongst pts with stage I and II TNBC regardless of BRCA status. Further studies are needed to evaluate whether similar results are observed with newer agents, such as platinums, PARP inhibitors and other targeted agents.
EarlyR genomic signature to predict pathological complete response following neoadjuvant anthracycline-taxane chemotherapy in estrogen-receptor positive (ER+) breast cancer.
Authors: Buechler Steven Allen , Badve Sunil S. , Gokmen-Polar Yesim 
Published: September 2018

579 Background: EarlyR is a prognostic signature computed from expression values of ESPL1, SPAG5, MKI67, PLK1 and PGR that stratifies ER+ breast cancer (BC) into EarlyRLow, EarlyRInt, and EarlyRHigh risk strata. Here, we show that EarlyR is also predictive of pathological complete response (pCR) following neoadjuvant anthracycline-taxane (AT) based chemotherapy. Methods: The ability of EarlyR gene signature to predict pCR was assessed in Affymetrix microarrays datasets (GSE25065, GSE25066, GSE20194, GSE20271; n = 541, pCR = 42 (7.8%) collectively labeled as Cohort A) derived from patients with ER+ breast cancer treated with neoadjuvant TFAC or FEC. For 2 of these datasets (GSE25065, GSE25066 (n = 291)) distant metastasis-free survival (DMFS) results were also available. The DMFS data in cohort A were compared to that of BC patients not treated with chemotherapy (denoted Cohort B, n = 1269) derived from ER+ samples from 7 GEO datasets (GSE3494, GSE7390, GSE12093, GSE6532, GSE2034, GSE11121, GSE17705). Results: In cohort A, EarlyR is a significant predictor of pCR (p = 1.0 x 10-6) (EarlyRLow, n = 273, pCR = 5, 1.8%; EarlyRInt, n = 11, pCR = 1, 9.1% and EarlyRHigh, n = 256, pCR = 36, 14.1%). Notably, 86% of the 42 cases with pCR have EarlyRHigh. Of the 291 patients with 8-year DMFS data from Cohort A, who had received chemotherapy, the survival of EarlyRHigh [0.79 (95%CI 0.70-0.89)] was nearly the same as that of EarlyRLow [0.82 (95%CI 0.74-0.90)]. In contrast, in cohort B, who were not treated with chemotherapy, 8-year DMFS is significantly (p = 5 x 10-15) lower in EarlyRHigh [0.57 (95%CI 0.51-0.64)] than in EarlyRLow[0.81 (95%CI 0.78-0.84)]. Conclusions: EarlyR is a strong predictor of pathological complete response in patients treated with TFAC or FEC. In addition, EarlyR also predicts poor DMFS outcomes for patients in EarlyRHigh not receiving chemotherapy. More importantly, neoadjuvant chemotherapy dramatically improved survival of patients in EarlyRHigh. These results document that EarlyR identifies a set of patients, EarlyRHigh, with a high risk of distant metastasis, who are also likely to respond favorably to chemotherapy.
A multicenter randomized controlled trial (RCT) of adjuvant chemotherapy (CT) in nasopharyngeal carcinoma (NPC) with residual plasma EBV DNA (EBV DNA) following primary radiotherapy (RT) or chemoradiation (CRT).
Authors: Chan Anthony T. C. , Hui Edwin Pun , Ngan Roger K.C. , Tung Stewart Yuk , Cheng Ashley Chi Kin , Ng Wai Tong , Lee Victor HF , Ma Brigette , Cheng Hoi Ching , Wong Frank C.S. , Loong Herbert H. F. , Tong Macy , Poon Daren MC , Ahuja Anil Tejbhan , King Ann Dorothy , Wang Ki , Mo Frankie , Zee Benny C.Y. , Chan Allen K.C. , Lo YM Dennis 
Published: September 2018

6002 Background: The benefit of adjuvant CT in NPC is unclear. Post-RT EBV DNA predicts poor survival and may be a biomarker of subclinical residual disease. We conducted a biomarker driven RCT using post-RT EBV DNA to select high risk NPC patients (pts) for adjuvant CT while sparing low risk pts from unnecessary toxicity. Methods: Eligible pts had biopsy proven NPC of AJCC (6th Ed) stage IIB-IVB, detectable EBV DNA ( > 0 copy/ml) at 6-8 weeks post-RT, no persistent locoregional disease or distant metastasis, ECOG 0 or 1, and adequate organ function. Pts were randomized with stratification for primary therapy (RT Vs CRT) and tumor stage (II/III Vs IV) to arm A (adjuvant cisplatin 40 mg/m2 and gemcitabine 1000 mg/m2, both given on D1+8 q3w x 6 cycles) or arm B (clinical follow-up). Primary endpoint was relapse free survival (RFS). With a hazard ratio (HR) of 2, 100 pts were required with a power of 0.8 and an alpha at 0.05. Results: From 9/2006 to 7/2015, 789 pts consented for EBV DNA screening, 218 (27.6%) pts had detectable EBV DNA, and 104 (13.2%) pts were randomized (arm A: 52; arm B: 52). The two arms were well balanced in baseline characteristics. 84.6% received prior neoadjuvant and/or concurrent CT and all received curative RT. Staging distribution: IIB 27.9%, III 37.5%, IVA 19.2%, IVB 15.4%. 8 pts refused adjuvant CT after randomization. Overall 69% and 50% completed 3 and 6 cycles of adjuvant CT respectively. After median follow up of 6.5 years (yr), the 3-yr and 5-yr survival outcomes were summarized in Table. Conclusions: In NPC pts who had residual EBV DNA after curative RT/CRT, adjuvant CT with cisplatin-gemcitabine did not improve survival. Clinical trial information: NCT00370890. [Table: see text]
Randomised phase-III-trial of concurrent chemoradiation (CRT) for locally advanced head and neck cancer (stage III-IVB): Comparing dose reduced radiotherapy (63,6 Gy) with paclitaxel/cisplatinum to standard radiotherapy (70,6 Gy) with fluorouracil/cisplatinum.
Authors: Fietkau Rainer , Iro Heinrich , Hecht Markus , Hofner Benjamin , Gefeller Olaf , Balermpas Panagiotis , Roedel Claus , Hautmann Matthias , Koelbl Oliver , Leber Horst , Salay Attila , Ruebe Christian , Breinl Peter , Krings Waldemar , Gripp Stephan , Wollenberg Barbara , Keerl Rainer , Schreck Ulrike , Siekmeyer Birgit , Grabenbauer Gerhard 
Published: September 2018

6016 Background: Concurrent CRT with 70.6 Gy is the standard treatment for locally advanced head and neck cancer (LA-SCCHN). There exist no prospective data on safety and efficacy of a reduced radiation (RT) dose. Methods: Pts with stage III-IVB LA-SCCHN were randomized 1:1 to receive 70.6 Gy with concurrent cisplatinum (20mg/m²/d IV on days 1-5 and 29-33) and fluorouracil (600 mg/m²/d CIV on days 1-5 and 29-33) (standard arm A) versus 63,6 Gy with intensified chemotherapy using concurrent cisplatinum (20mg/m²/d IV on days 1-4 and 29-32) and paclitaxel (20mg/m²/d IV on days 2, 5, 8, 11 and 25, 30, 33, 36) (experimental arm B). After a planned interim analysis recruitment was stopped due to statistical reasons. Results: Between 06/2010 and 02/2015 a total of 221 pts were randomized with 105 pts receiving treatment in arm A and 112 in arm B (4 pts dropped out). Median follow-up was 38 months. Pts’ characteristics: Oral cavity (15%), oropharynx (54%), hypopharynx (28%), larynx (14%); 17 pts had more than one primary site; tumor stage: III (14%), IV (86%); HPV-status (p16) was positive in 20%, negative in 38%, currently pending in 42%. A total of 96 PFS-related events occurred. 3-year PFS (ITT) was 58% in the standard arm A and 48% in experimental arm B (p = 0.454). 3-year OS (ITT) was 64% in arm A and 59% in arm B (p = 0.688). 3-year rates of distant metastases, loco-regional recurrences and death were 10% vs 12%, 17% vs 21% and 15% vs 19% for pts in arm A and B, respectively. As for the p16-positive subgroup, 3-year PFS/OS were 77%/76% in arm A (n = 21) and 69%/80% in arm B (n = 22), respectively. Grade 3+ hematologic adverse events during therapy (arm A/arm B): Anemia 11%/4% (p = 0.038); neutropenia 40%/16% (p < 0.001); thrombocytopenia 8%/3% (p = 0.130). Conclusions: These preliminary results indicate that pts receiving concurrent CRT for LA-SCCHN did not benefit from a lower total RT dose of 63.6Gy despite intensified chemotherapy. However, in the subgroup of p16-positive pts a reduced RT dose may be sufficiently effective. Clinical trial information: NCT01126216.
Randomized, double-blind, placebo-controlled, phase II trial of first-line platinum/docetaxel with or without erlotinib (E) in patients (pts) with recurrent and/or metastatic (R/M) head and neck squamous cell carcinomas (HNSCCs).
Authors: William William Nassib , Feng Lei , Kies Merrill S. , Ahmed Salmaan , Blumenschein George R. , Glisson Bonnie S. , Massarelli Erminia , Johnson Faye M. , Lu Charles , Papadimitrakopoulou Vassiliki , Gold Kathryn A. , Theriault Rachel Leigh , Heymach John , Kim Edward S. 
Published: September 2018

6017 Background: In a single-arm, phase 2 study, we previously demonstrated that in pts with R/M HNSCC, cisplatin, docetaxel and E improved progression-free survival (PFS) compared to historical data (Kim et al., ASCO 2006). Herein, we evaluated this regimen in a single center, randomized, phase 2 trial. Methods: Pts with R/M HNSCC, with a performance status (PS) 0-2, were randomized (1:1) to receive up to 6 cycles of first-line chemotherapy with cisplatin 75 mg/m2 (or carboplatin AUC 6) and docetaxel 75 mg/m2 i.v. on day 1 every 21 days, plus placebo (P) vs. E 150 mg p.o. daily, followed by maintenance P or E until disease progression. The primary endpoint was PFS. With 120 pts, the study had 80% power to detect an improvement in median PFS from 3.0 to 4.9 months with a two-sided type I error rate of 0.1. Results: From 05/2010 to 07/2015, 120 pts were randomized to the P (N = 60) or E (N = 60) groups. All pts but one initiated treatment and were eligible for evaluation of the primary endpoint – 92 males; median age 62 years; 52 oropharynx, 40 oral cavity, 19 larynx, 8 hypopharynx cancer pts; 86 current/former smokers; 43 with recurrence within 6 months of completion of local treatment; 27 with prior exposure to EGFR inhibitors. Median PFS was 4.4 vs. 6.1 months for the P and E groups, respectively (hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.42-0.95 months, p = 0.026). Response rates were 44% vs. 56% for P vs. E (p = 0.21). Median overall survival (OS) for P- and E-treated pts was 13.7 vs. 17.0 months (HR = 0.67, 95% CI 0.43-1.04, p = 0.07). Benefits from E on PFS and OS were more pronounced in pts with oropharyngeal tumors (p≤0.05 for interaction). In the E group, first-cycle rash grade 2-4 (34% pts) was associated with longer OS (HR = 0.40, p = 0.02). E-treated pts experienced a higher incidence of grade 3-4 adverse events (33.9 vs. 53.3%), including diarrhea (3 vs.17%), dehydration (5 vs. 15%), nausea (5 vs. 14%), rash (0 vs. 12%). Conclusions: This study met its primary endpoint. Addition of E to first-line platinum/docetaxel improved PFS and OS. This regimen may warrant further evaluation in randomized, phase 3 trials. Clinical trial information: NCT01064479.