bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic sentinel lymph node biopsy in patients with invasive squamous cell carcinoma of the penis: A prospective study of the outcome of 500 inguinal basins assessed in a single institution.
Authors: Lam Wayne , Alnajjar Hussain M , La-Touche Susannah , Perry Matthew , Corbishley Catherine M , Pilcher James , Heenan Sue , Watkin Nicholas 
Published: March 2020

4640 Background: Dynamic sentinel node biopsy (DSNB) in combination with ultrasound scan (USS) has been the technique of choice at our centre since 2004 for the assessment of non palpable inguinal lymph nodes in patients with squamous cell carcinoma of the penis (SCCp). Sensitivity/false-negative rates may vary depending on whether results are reported per patient or per node basin and with and without USS. The purpose of this study was to determine the long-term outcome of DSNB and ultrasound-guided fine needle aspiration cytology (FNAC) in our cohort of newly diagnosed patients and to analyse any variation in sensitivity of the procedure. Methods: A prospective cohort study over 6 years (2004 to 2010). Inclusion criteria: New diagnosis SCCp, T1G2 or greater definitive histology, non-palpable nodes in inguinal basin. Exclusion: patient with persistent/untreated local disease. Sensitivity of the procedure was calculated, per node basin, per patient, DSNB alone, USS/DSNB combined. Minimum follow up 12 months. Results: 500 inguinal basins in 264 patients underwent USS+/-FNAC and DSNB. 70 (14%) positive inguinal basins in 57(22%) patients were identified. 9 (2%) inguinal basins had no tracer uptake. 2 inguinal basins were confirmed false negative at 8 and 12 months. 2 inguinal basins had positive USS+FNAC and negative DSNB. Overall sensitivity of the technique is reported in the table. Conclusions: DSNB in combination with USS has excellent performance characteristics to stage patients with clinically node-negative penile cancer with a 3% false negative rate. USS improves performance by 4% over DSNB alone. There is no difference in performance of the combined technique if it is reported per node basin or per patient. [Table: see text]
Phase I trial of NY-ESO-1/LAGE1 peptide vaccine for metastatic castration resistant prostate cancer (mCRPC).
Authors: Hayes Teresa Gray , Sonpavde Guru , Wang Mingjun , Wang Yicheng , Joe Teresa , Mims Martha P. , Ittmann Michael M. , Wheeler Thomas M. , Gee Adrian P. , Wang Rongfu F 
Published: March 2020

4643 Background: The NY-ESO-1 and LAGE-1 antigens are amplified in malignancies including prostate cancer. Preclinical induction of immune responses and anti-tumor activity has been demonstrated upon administration of these peptides. A phase I/II clinical trial evaluated the feasibility of a combined HLA class-I and class-II peptide vaccine in mCRPC. Methods: Men with progressive mCRPC, Performance Status ≤2, PSA ≥10 ng/ml and had appropriate HLA class I (A2) and class II haplotypes (DR4, DP4, DR13) were eligible. Three groups with 3 patients each received the vaccine subcutaneously every 2 weeks for 6 doses. Group 1 was treated with a peptide directed at a HLA class I haplotype (HLA A2), Group 2 was treated with a peptide reacting to a HLA class II haplotype (DR4, DP4, or DR13), and Group 3 received peptides directed at both Class I and II haplotypes. Group I and Group II received 1 dose of 1000 mcg and Group III received doses of 1000 mcg for each of 2 peptides. Androgen-deprivation was continued. Results: Of 14 patients enrolled, all were evaluable for toxicities and 9 patients completed all 6 treatments per amended protocol and were evaluable for efficacy. The median baseline PSA was 85.19 ng/ml. Four patients were chemo naive and 5 were post-docetaxel. One patient had a grade 5 event (myocardial infarction) unlikely therapy-related. Potential therapy related toxicities were local grade 1 injection site erythema (n=5), fatigue (n=2), flu-like symptoms (n=1), myalgias (n=1), anorexia (n=1), nausea (n=1) and leukocytosis (n=1). The median PSA doubling time pre-therapy and during therapy were 3.1 and 4.92 months, respectively. The PSA-DT was prolonged compared to baseline in 6 patients, including a negative PSA slope in 2 patients. Antigen-specific immune response determined by ELISPOT was observed, and its association with slowing of PSA-doubling time will be further examined. Conclusions: In men with mCRPC, HLA class-I and/or class-II restricted NY-ESO-1 and LAGE-1 peptides administered subcutaneously demonstrated excellent tolerability, slowing of PSA doubling time and antigen-specific immune responses. Further development of peptide vaccines alone or in combination with other regimens may be warranted.
Prognostic stratification of post-docetaxel metastatic castration resistant prostate cancer (mCRPC) from a phase III randomized trial.
Authors: Sonpavde Guru , Pond Gregory Russell , Clarke Stephen John , Vardy Janette L. , Wang S. L. , Paolini Jolanda , Lechuga Mariajose , Michaelson M. Dror , Smith Matthew Raymond , Chen Isan , Maneval Edna Chow 
Published: March 2020

4644 Background: A prognostic model for mCRPC post docetaxel is necessary to guide therapy. We retrospectively analyzed a phase III trial enrolling progressive mCRPC following docetaxel to construct a prognostic model. Additionally, we studied the impact of neutrophil-lymphocyte ratio (NLR), a potential marker for inflammatory and immune state. Methods: A phase III trial (SUN-1120) comparing prednisone combined with sunitinib (N=584) or placebo (N=289) for mCRPC following docetaxel-based chemotherapy was evaluated. The treatment arms were combined for analysis, since no statistical difference was observed in the primary endpoint of overall survival (OS). A logarithmic transformation was applied to non-normal factors. The Kaplan-Meier method was used for OS estimation. To identify an optimal prognostic model for survival, we used a Cox proportional hazards regression methods with forward stepwise selection, stratifying for ECOG PS, progression type (PSA or radiographic) and treatment group. A risk score was calculated and patients were categorized into risk groups to assess model performance. Results: Data from patients without missing data (n=806) were used to construct an optimal model. The factors used in the model that remained individually significant in multivariate analysis were: log-LDH (HR 2.77 [95% CI=2.23, 3.44], p<0.001), hemoglobin (0.81 [0.76, 0.87], p<0.001), log-NLR (1.63 [1.38, 1.92], p<0.001), >1 organ involved (1.53 [1.24, 1.88], p<0.001), log-alkaline phosphatase (1.14 [1.01, 1.30], p=0.041) and log-PSA (1.07 [1.00, 1.13], p=0.036). No clear cutpoints were identified; thus, these prognostic factors were used to group patients into 3 equally sized risk categories. Low, medium and high risk patients (n=268-270 per group) had median (95% CI) OS estimates of 23.7 (21.4-not reached), 13.5 (11.6-15.8) and 7.3 (6.3-8.4) months, respectively. Conclusions: A prognostic risk model with readily available variables significantly discriminated between outcomes in post-docetaxel mCRPC and may provide valuable information in future studies. High NLR was associated with an independent poor prognostic impact, and warrants prospective validation.
Molecular determinants of outcome with mTOR inhibition in endometrial cancer (EC).
Authors: Mackay Helen , Eisenhauer Elizabeth A. , Kamel-Reid Suzanne , Clarke Blaise , Walsh Wendy , Karakasis Katherine , Salvesen Helga B , Oza Amit M. 
Published: March 2020

5010 Background: Deregulation of PI3K/AKT/mTOR signaling plays a significant role in EC biology. NCIC CTG has completed three phase II trials of 2 mTOR inhibitors (temsirolimus and ridaforolimus) in EC (IND 160A, IND 160B, IND192) demonstrating anti-tumor activity. PTEN expression, however, was not associated with response. In this study we are conducting additional molecular analyses on samples obtained from patients (pts) participating in these trials to identify mutations or other findings associated with mTOR response. Methods: Formalin fixed paraffin embedded (FFPE) tumor samples were collected from pts treated on the three trials. Tumor DNA was isolated and mutational profiling (MP) was performed using theOncoCarta Panel v1.0 which can detect 238 mutations in 19 oncogenes including AKT1, 2, BRAF, CDK-4, EGFR, ERBB2, MET, H-, K-, N- RAS, PDGFRA, PIK3CA, RET. All mutations were verified by Sanger sequencing. For each gene found to be mutated in at least 1 patient, the relationship between presence/absence of mutations in that gene and objective anti-tumor response (RR) was assessed (RR vs. no response; early progression (PD) vs. no PD) using Fisher's exact test. In addition, the presence of any mutation vs. no mutations was assessed in relationship to the same clinical outcomes. Results: MP was feasible in 73 of the 94 eligible pts treated on the three trials. 44% (32 pts) had a mutation in at least one gene: 21 pts (29%) in PIK3CA, 10 (14%) KRAS, 4 (5%) MET, 3 (4%) NRAS, 3 (4%) AKT and 1(1%) EGFR. 9 pts (12%) had > 1 mutation. No significant correlations were seen, in individual trials or within the pooled data set of 3 studies, between the presence/absence of any mutation and RR (p=1.0) or early PD (p=1.0). No significant association was seen between the presence of mutations within individual genes and RR or PD (including PIK3CA). Of interest, no response was observed in any of the 13 pts with a Ras mutation (non-significant). Additional analyses involving gene expression (including stathmin) and correlation of MP with tumor morphology are underway. Conclusions: Mutations are common in EC but we have not identified a statistical association between presence of mutations in PIK3CA or any other gene and response to mTOR inhibition. Further analyses are ongoing.
Phase I trial of metronomic oral topotecan in combination with pazopanib utilizing a daily dosing schedule to treat recurrent or persistent gynecologic tumors.
Authors: Tillmanns Todd D. , Reed Mark E. , Privett Melissa C. , Johns Amanda L. , Walker Mark S. , Houts Arthur C. 
Published: March 2020

5014 Background: Metronomic oral topotecan has antiangiogenic properties. Oral pazopanib is also a potent inhibitor of VEGF angiogenesis with clinical benefit. This study investigated the safety and efficacy of daily topotecan and pazopanib. Methods: This phase I, single-center, open-label, dose ranging study comprised 28-day cycles of daily oral topotecan/pazopanib at dose levels of 0.50/400, 0.25/800, 0.25/600, and 0.25/400 mg. A standard 3+3 dose escalation design was used. Dose limiting toxicity (DLT) was defined as ≥ grade 3 adverse event (AE) occurring in cycle 1, noncompletion of cycle 1 at prescribed dose, or inability to start cycle 2 as scheduled due to toxicities. Imaging was conducted after every 2 cycles for response assessment. Confirmed responses were evaluated per RECIST 1.0. Results: 25 extensively pretreated patients (pts) with gynecologic tumors (6 cervical, 7 endometrial, 8 ovarian, 4 other) were enrolled. Mean age was 61 years; 19 Caucasian, 6 African American. Median number of cycles received was 4 (range 1-19). DLTs occurred ≥ 2 pts for A (2/6), B (2/7), C (3/7). For level D, 1/5 had a DLT, but one dose level C pt with a DLT received level D dosing due to unavailability of pazopanib. 9/25 pts had any serious adverse event (SAE), and respiratory SAEs were most common (4/16 SAEs). Nausea, fatigue, dysgeusia, diarrhea, and vomiting were the most common conditions reported as non-serious AEs. The Table shows best overall response (28%) by dose level. Conclusions: DLTs in dose levels C and D were effectively managed with minor dose and schedule adjustments. 4 pts with DLTs at these doses remained on treatment for 4, 5, and 6 months, with one pt still on treatment at 9 months. Given the initial biologically favorable signal in this heavily pretreated group and low toxicity, we recommend a randomized phase II trial to define efficacy using the 0.25/600 regimen allowing for dose reduction if needed. [Table: see text]
Safety of front-line bevacizumab (BEV) combined with weekly paclitaxel (wPAC) and q3w carboplatin (C) for ovarian cancer (OC): Results from OCTAVIA.
Authors: Gonzalez-Martin Antonio , Gladieff Laurence , Tholander Bengt , Stroyakovsky Daniel , Gore Martin Eric , Segalla J.G.M. , Reyners An K.L , Kovalenko Nadezhda , Oaknin Ana , Selle Frédéric , Bollag David T. , Pignata Sandro ,   OCTAVIA Investigators
Published: March 2020

5017^ Background: In two randomized phase III trials in OC (GOG218 and ICON7), front-line BEV + q3w PAC + q3w C followed by BEV alone significantly improved progression-free survival (PFS) vs chemotherapy (CT) alone. In the Japanese NOVEL trial, wPAC + q3w C was more effective than q3w PAC + C, but toxicity limited CT delivery. The single-arm OCTAVIA study evaluated front-line BEV + wPAC + q3w C. Methods: Patients (pts) received 6–8 cycles of BEV (7.5 mg/kg, d1) + wPAC (80 mg/m2 d1, 8, 15) + C (AUC6, d1) iv q3w, with BEV q3w continued alone for a total of up to 17 cycles (1 y) as front-line therapy for newly diagnosed OC (FIGO stage I–IIa [grade 3/clear cell] or stage IIb–IV [any grade]). The trial was designed to recruit a pt population similar to that enrolled in ICON7. The primary endpoint was PFS. Secondary endpoints included response rate, duration of response, overall survival, biological progression-free interval, and safety. Previously we reported safety findings from the concurrent CT phase. Here we present final safety results from the entire treatment period. Results: Between Jun 2009 and Jun 2010, 189 eligible pts were enrolled. Baseline characteristics: median age 55 y (range 24–79 y); ECOG 0 74%; FIGO stage I/II/III/IV 10%/10%/63%/17%; serous/clear cell/mixed 65%/6%/6%; 71% optimally debulked. Pts received a median of 6 CT cycles (range 1–8) and 17 BEV cycles (range 0–18). Of the 168 pts who received single-agent BEV, 135 completed 1 y of therapy. In the entire treatment period, BEV was discontinued for adverse events (AEs) in 12% and disease progression (PD) in 10%. The most common grade ≥3 hematologic AEs were neutropenia (60%), anemia (8%), and thrombocytopenia (7%). The incidences of grade ≥3 AEs of special interest for BEV were: hypertension 4.2% (grade 2/3/4: 9.0%/3.2%/1.1%); thromboembolic events 6.3% (grade 3/4: 3.7%/2.6%); bleeding 0.5% (grade 3), wound-healing complications 0.5% (grade 3), and GI perforation 0.5% (grade 4). There was no grade ≥3 proteinuria or fistula/abscess. At the time of data cut-off, 9 pts had died, all from PD. Conclusions: BEV combined with wPAC is feasible and well tolerated. BEV AEs were no more frequent with wPAC in OCTAVIA than with q3w PAC in ICON7.
Efficacy and safety of the APE (actinomycin D, cisplatin, etoposide) regimen for the management of high-risk gestational trophoblastic neoplasia.
Authors: Lhomme Catherine , Even Caroline , Duvillard Pierre , Pautier Patricia , Floquet Anne , Kerbrat Pierre , Troalen Frederic , Rey Annie , Balleyguier Corinne , Morice Philippe , Fizazi Karim , Droz Jean Pierre 
Published: March 2020

5028 Background: Patients (pts) with high risk gestational trophoblastic neoplasia (GTN) or who fail low risk single agent chemotherapy (CT) require multi agent CT to be cured. The most common regimen is etoposide (E), methotrexate and actinomycin D (A) alternating weekly with cyclophophamide and vincristine (EMA/CO). Cisplatin (P) is a very active drug but its role is controversial and usually restricted to second line. We report results of a platinum based therapy: APE. Methods: We evaluated the efficacy and safety on 103 pts treated at Institut Gustave Roussy (IGR) (n=80) or other French centers (n=23) between 1983 and 2010 with APE for high risk GTN (defined by IGR criteria [Azab, Cancer, 1988] and/or FIGO score >6). Pts with brain metastasis were excluded. Results: Efficacy was evaluated on 59 pts treated for high risk GTN in first line, and on 39 pts in >2nd line including 13 pts after multi agent CT. We excluded pts with placental site trophoblastic tumors (n=2), or with FIGO score <7 and without IGR criteria (n=3). Complete remission (CR) rate was 95%. Seven pts (7 %) relapsed and a second CR was obtained for all with surgery and/or CT. Only one patient died due to GTN, after successive CRs obtained with 3 regimens. Five year overall survival (median follow-up 6.6 years) was 98%. Toxicity was evaluated on 95 pts. No toxic death occurred. Given good efficacy and to avoid acute hematotoxicity and long-term G>1 neuro and ototoxicity APE regimen was modified as detailed in the Table (below). Long-term neuro (5 pts, G1), oto (2 pts, G1 and 2 pts, G2) and renal toxicities (1 pt, G1 ) were recorded. No long-term G2 toxicities were observed with APE3. One pt developed an AML 4 after 4cy APE and 6 cy EMA/CO. 37 pts of 40 who wished to be pregnant succeeded and all of them had at least one live birth. Conclusions: With a 98% long-term overall survival rate, an excellent reproductive outcome, and no detectable long-term toxicity, APE-3 should be regarded as an alternative standard option to EMA/CO for high-risk GTN. [Table: see text]
Application of micro-RNA (miRNA) expression profiles for prognostication in low-risk endometrial carcinoma (LEC).
Authors: Weberpals Johanne Ingrid , Snowdon Jaime , Bougie Olga , Zhang Xiao , Tron Victor , Childs Timothy , Bambury Ian Garfield , Feilotter Harriet 
Published: March 2020

5032 Background: Reliably predicting which LEC patients are most likely to recur is a challenge for the clinician with implications on adjuvant therapy. MiRNAs have been exploited for diagnosis and prognostication in a number of malignancies. We hypothesize that miRNA expression profiles differ in tumors from patients with recurrence compared to those without recurrence. Methods: The inclusion criteria for this study are informed consent, stage 1 disease, grade 1 or 2 tumors and endometrioid histology. RNA was extracted from formalin-fixed paraffin-embedded tissues and miRNA profiling was done using Agilent Human miRNA. Differentially expressed miRNAs were identified using GeneSpring GX software and the two groups were compared using the student t-test. Results: The expression levels of 866 miRNAs were determined from LEC patients with recurrence (n=15) and without recurrence (n=16). The mean follow-up interval was 61.5 months. The average age of cancer diagnosis for patients with and without recurrence was 60.2 (range 42-75) and 59.7 (range 44-86), respectively (p=0.91). Three of 15 patients with recurrence and 6 of 16 patients without recurrence received adjuvant brachytherapy following their primary surgery (p=0.43). 17 miRNAs were identified which can distinguish between the tumors with recurrence and those without recurrence (p<0.05). MiR-146a, miR-18a, miR-222, and miR-30a showed the highest fold change difference (>5 fold) in the tumors with recurrence compared to that did not recur. A decision tree prediction model for recurrent LEC was developed where a miRNA cutoff was used as a branch in the decision tree. This model identified those patients who were most likely to recur based on the expression of 4 dysregulated miRNAs (miR-222, miR-361-3p, miR-181c and miR-125b). Conclusions: These preliminary results show the miRNA expression profile differs among LEC and can be used to distinguish an aggressive sub-group. Should future validation studies confirm this result, this information would be valuable in the design of a biomarker study to help decide which patients would benefit most from extended adjuvant treatment.
Intrinsic subtype and its clinical significance in early node-negative breast cancer: Results from two randomized trials of adjuvant chemoendocrine therapy.
Authors: Millar Ewan K.A , Coates Alan Stuart , O'Toole Sandra , Selinger Cristina , Musgrove Elizabeth A. , Yan Max , Viale Giuseppe , Regan Meredith M. , Price Karen N. , Sun Zhuoxin , Castiglione Monica M. , Colleoni Marco , Gelber Richard D. , Goldhirsch Aron , Sutherland Robert L. ,   International Breast Cancer Study Group
Published: March 2020

504 Background: Gene expression profiling has identified four main intrinsic subtypes of breast cancer which have distinct clinical behaviours and responses to therapy. A simplified immunohistochemical (IHC) panel can provide meaningful discrimination and help guide patient management. Methods: Using tissue microarrays (TMA) created from two randomized trials of adjuvant chemoendocrine therapy in node negative early breast cancer (IBCSG VIII and IX,n= 1220) we assessed intrinsic subtype as follows: “luminal A” (LA): ER and/or PR present, Ki-67 low (<median: 19%), HER2-; “Luminal B” (LB): ER and/or PR present, Ki-67 high(>=19% median) and/or HER2+ (IHC 3+ or FISH amplified); HER2 enriched: ER and PR negative, HER2 positive (IHC 3+ or FISH amplified), Triple Negative (TNP): ER, PR and HER2 negative. p53+ and high cyclin D1 expression were then assessed to determine if they provided any further additive discriminatory value. Results: The standard definitions of intrinsic subtype demonstrated a significant difference in disease-free survival between the subtypes in both trials VIII and IX (p= 0.02), but this was not significant in multivariate analysis. The discrimination between luminal A and B tumors could not be improved upon by the addition of p53 or cyclin D1 expression. The standard definitions demonstrated that TNP and HER2-enriched tumors benefited from the addition of chemotherapy to endocrine therapy, but LA and LB did not. p53+ was associated with a poorer prognosis in ER+ luminal tumors but improved prognosis in ER- non-luminal tumors (Interaction p = 0.002). Conclusions: Intrinsic subtyping using a panel of ER, PR, HER2 and Ki67 provides meaningful prognostic information to help guide patient management in early breast cancer. Whilst it predicts benefit from the addition of chemotherapy in TNP and HER2-enriched tumors it did not in this series do so for LB. Although p53 status did not improve the definition of luminal tumors, p53+ appeared to have a divergent effect on outcome dependent on ER status.