bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of high-risk HPV in urine of high- and low-risk populations in India
Authors: Robbins D. , Garg D. , Li J. , Melkonyan H. 
Published: August 2020

5581 Background: Infection with high-risk HPV is involved in 90%-100% of cervical cancers. HPV detection in cervical cells, used as a supporting test for Pap smear positive patients, are much more sensitive than cytology but less specific for ongoing cervical cancer. Cervical cancer is one of the most common female tumors in countries lacking a screening program such as India. In this study we investigate the feasibility of a urine-based HPV DNA test. Methods: Matching urine and cervical samples were collected from 270 high-risk subjects from STD clinics or district brothels in West Bengal, and 50 low-risk subjects with no known predisposition to disease recruited in Mumbai. The Xenomics HPV DNA test involves isolation of DNA from urine and specific PCR amplification of the HPV E1 region to detect the presence of high-risk HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68. Results were compared to the hc2 high-risk HPV DNA Test (QIAGEN). Discordant samples were resolved by DNA sequencing. Results: Of 320 patients, 248 samples (77.5%) were concordant between the Xenomics and hc2 assays. Of the discordant samples reactive by Xenomics but nonreactive by hc2, 31/38 (81.6%) contained high-risk HPV by DNA sequencing. 10 out of 34 (29.4%) of samples detected by hc2 but not by Xenomics were shown to contain high-risk HPV. Using DNA sequencing as the gold standard, the Xenomics test false negative and false positive rates were 10/180 (5.6%) and 7/140 (5.0%), respectively. The hc2 assay had a false negative and false positive rate of 31/184 (16.8%) and 24/136 (17.6%), respectively. Conclusions: HPV DNA can be isolated from urine samples and detected with sensitivity and specificity equal to or better than current assays based on cervical scraping. [Table: see text]
A phase II study of weekly neoadjuvant chemotherapy followed by radical chemoradiation for locally advanced cervical cancer
Authors: McCormack M. , Ledermann J. A. , Hall-Craggs M. A. , Symonds R. P. , Warwick V. , Simonds H. , Fernando I. , Hackshaw A. 
Published: August 2020

5586 Background: Chemoradiation (CRT) is the standard of care for locally advanced cervical cancer but survival is poor among women with large tumours, advanced stage, or positive nodes. Neoadjuvant chemotherapy (NACT) prior to CRT to down-stage tumours and lengthen the exposure to systemic treatment is designed to improve outcome. Methods: Patients (pts) with locally advanced cervical cancer received dose-dense carboplatin (AUC2) and paclitaxel (80 mg/m2) weekly, for 6 cycles, followed by CRT (external and brachytherapy) in week 7 with weekly cisplatin (40 mg/m2). The primary end-point was complete and partial response rate (RR) 12 weeks post CRT. Secondary objectives were RR for NACT at 6 weeks, toxicity and survival. The target RRs were 50% and 85% for NACT and post CRT (12-weeks) respectively. Results: Baseline characteristics were: median age at diagnosis 43 yrs (23–71); 74% squamous-, 20% adeno- and 6% adenosquamous carcinomas; FIGO stage IB2 (11%), II (50%), III (33%), IV (6%). The trial closed in Oct 08 with 46 pts. Of the first 36 pts enrolled 9 failed to complete protocol therapy (7 did not complete 6 NACT cycles, 2 did not complete the pre-specified minimum of 4 cycles of concomitant cisplatin). Using data currently available, the RR associated with NACT is 72% (95% CI 53–86%), and 81% at 12 weeks (95% CI 63–92%). Nonhaematological grade 3/4 toxicity was rare (<5%). There was grade 2 alopecia in 25% pts. Grade 3 and 4 haematological toxicity was seen in 10% and <3% of pts respectively. Updated results, including survival, will be presented for all pts. Conclusions: Dose-dense weekly NACT chemotherapy with carboplatin and paclitaxel followed by radical CRT is associated with a high response rate and is feasible. This approach merits further investigation in a phase III trial. [Table: see text]
Utilization of Internet-based survivorship care plans by survivors of gynecologic cancers
Authors: Hill-Kayser C. E. , Vachani C. , Hampshire M. K. , Jacobs L. A. , Metz J. M. 
Published: August 2020

5592 Background: Survivors of gynecologic cancers may be at risk for cancer-related late-effects, including fatigue, pain, second malignancy risk, and sexual side effects. The Institute of Medicine has recommended survivorship care plans (SCP) for all cancer survivors. Methods: A program for creation of SCP, OncoLife, is publicly accessible through OncoLink ( www.oncolink.org ), serving over 3.9 million pages/month to 385,000 unique IP addresses (August 2008). Users responding to 17 queries regarding demographics, diagnosis, and treatment receive comprehensive, individualized guidelines for future care. User data is maintained anonymously and securely, with IRB approval. Results: From May 2007-November 2008, 3,343 individuals completed OncoLife surveys. Survivors of gynecologic cancers represented 8% (n = 272; 58% ovarian, 24% endometrial, 19% cervical). Median ages at diagnosis of ovarian, endometrial, and cervical cancer were 50, 51, and 35 yrs, respectively, and median current ages 53, 55, and 47. Surgery was undergone by 98% of ovarian, 97% of endometrial, and 81% of cervical cancer survivors, and chemotherapy/ radiotherapy by 91%/12%, 51%/59%, and 67%/67%, respectively. Known genetic syndromes were reported by 13% of ovarian cancer survivors, compared to < 1% of endometrial/ cervix cancer survivors (p = 0.0006). Of all gynecologic cancer survivors, 53% reported being followed by an oncologist, 14% a primary care provider (PCP), and 27% both. Only 7% had received survivorship information previously. Conclusions: Most survivors of gynecologic malignancies have undergone multimodality treatment and may particularly benefit from SCP guidelines. Most do not receive follow-up care from both an oncologist and PCP, and few have received survivorship information. Gynecologic cancer survivors appear willing to use this tool; future iterations will focus on further individualization of guidelines, and improving access to underrepresented populations. No significant financial relationships to disclose.
Evaluation of preoperative positron emission tomography with computed tomography (PET-CT) for detecting lymph node metastasis in gynecologic carcinoma
Authors: Murakami F. , Ogawa N. , Yamazaki A. , Sakurai S. , Ishiya T. , Katase K. , Shimizu Y. , Tanada S. 
Published: August 2020

5593 Background: To evaluate the sensitivety, specificity, and accuracy of PET-CT for detecting lymph node metastasis in gynecologic carcinoma. Methods: Between May 2007 to August 2008, 36 consecutive patients (pts) with cervical carcinoma, endometrial carcinoma and epithelial ovarian carcinoma were enrolled. All pts underwent PET-CT prior to the surgery of systematic pelvic and paraaortic lymphadenectomy. For pathological metastatic lymph nodes, the size of intranodal tumor deposits (maximum diameter of metastatic foci in each lymph node) were recorded. Results: The total number of pelvic lymph nodes (PLNs) plus paraaortic lymph nodes (PANs) removed was 2426. The median number of removed lymph nodes (LNs) was 67 each pts (range: 25 to 102). The number of involvement LNs was 79 (3.5%). The sensitivity, specificity and accuracy of preoperative PET-CT to detect LN metastasis were 24%, 99.9%, and 97.5%, respectively. The sensitivity of PLNs and PANs were 39.5% and 7.3%, respectively. The sensitivity of squamous cell carcinoma (SCC) were 35.7%, that of adenocarcinoma were 8.1%. FDG-PET detected 100% of intranodal tumor deposits > or =10 mm, whereas tumor deposits smaller than 5 mm were not detected. Conclusions: The results of our study revealed 76% underdiagnosis (overlooking) in evaluation of preoperative PET-CT in LN metastasis. Particularly, tumor deposits smaller than 5 mm were not detected at all. Using PET-CT for detecting small LN metastasis in gynecologic carcinoma may be unreliable so far. However we found that PLNs are comparatively easy to be detected than PANs, and SCC are comparatively easy to be detected than adenocarcinoma. The improved usability and application of PET-CT for detecting LN metastasis in gynecologic carcinoma have to keep researching constructively. No significant financial relationships to disclose.
Randomized phase III trial of adjuvant epicirubicin (E) followed by cyclophosphamide, methotrexate, and fluorouracil (CMF) or CMF followed by E in patients with N- or ≤ 3 N+ rapidly proliferating breast cancer (RPBC)
Authors: Amadori D. , Schittulli F. , Paradiso A. , Scarpi E. , Sismondi P. , Ravaioli A. , Rocca A. , Maltoni R. , Serra P. , Silvestrini R. 
Published: August 2020

560 Background: Antimetabolites are active in proliferating cells, and the adjuvant schedule CMF is highly effective in RPBC, whereas the sequential administration of doxorubicin (D) and CMF is superior to CMF–>D, especially in indolent tumors. In a phase III study, we evaluated whether adjuvant E followed by CMF is superior to the inverse sequence in RPBC. Methods: Patients with N-, T > 1 cm or ≤ 3 N+ and any T RPBC (defined by thymidine labeling index or grade or S-phase or Ki67/MIB1) were randomized to receive E (100 mg/m2 i.v. d 1, q 21 days for 4 cycles) followed by CMF (600, 40, 600 mg/m2 i.v. d 1 and 8, q 28 days for 4 cycles) (arm A) or CMF followed by E (arm B) or CMF (600, 40, 600 mg/m2 i.v. d 1 and 8, q 28 days for 6 cycles) (arm C). Arm C was closed after the EBCTCG 2000 meta-analysis (data not shown). The main endpoint was overall survival (OS), and the study had 80% power to detect a 7% absolute increase in 5-year OS with 400 patients per arm. Results: From November 1997 to December 2004, 1066 patients were enrolled (arms A/B/C: 440/438/188): N- 53%, estrogen receptor positive 63%, grade 3, 77%. At a median follow up of 69 months, 5-year disease-free survival was 80% in both arms (A and B) (p = 0.93, logrank test), with adjusted hazard ratio (AHR) 0.99 (95% CI 0.73–1.33, Cox model), and OS was 91% in arm A and 93% in arm B (p = 0.66, logrank), with AHR 0.88 (95% CI 0.58–1.35, Cox model). Adverse events were similar, apart from a small increase in grade 4 neutropenia in arm B. Conclusions: No relevant differences in clinical outcome were observed with the 2 different sequences. Further subgroup analyses are ongoing to verify the efficacy of each sequence as a function of biomolecular and hormonal profiles. No significant financial relationships to disclose.
Randomized, blinded, placebo-controlled trial of acupuncture for the management of aromatase inhibitor-associated joint symptoms in women with early-stage breast cancer
Authors: Crew K. D. , Capodice J. , Greenlee H. , Brafman L. , Fuentes D. , Awad D. , Hershman D. L. 
Published: August 2020

571 Background: Aromatase inhibitors (AIs) have become the standard of care for the treatment of postmenopausal, hormone-sensitive breast cancer (BC). However, patients receiving AIs may experience joint symptoms which can lead to early discontinuation of this effective therapy. We examined whether acupuncture improves AI-induced arthralgias in women with early stage BC. Methods: This study is a randomized, single-blinded trial of true vs sham acupuncture twice weekly for 6 weeks in postmenopuasal women with early stage BC and self-reported musculoskeletal pain related to adjuvant AI therapy. The active intervention included full body/auricular acupuncture and a joint-specific point prescription, whereas the sham arm involved superficial needle insertion at nonacupoint locations. Outcome measures included the Brief Pain Inventory-Short Form (BPI-SF), Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC), and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands (M-SACRAH) obtained at baseline, 3 and 6 weeks. Lower scores reflect improvement in symptoms. Results: Of 43 women enrolled, 38 were evaluable at 6 weeks. Baseline characteristics were comparable between the groups. Median age: 57 (37–77); White/Hispanic/Black/Asian: 15/21/1/1; median body mass index (kg/m2): 29 (18–45). True acupuncture was associated with about a 50% decrease in mean BPI-SF scores, whereas no change from baseline was observed for the sham acupuncture group (see table). Similar findings were seen for the WOMAC and M-SACRAH pain, stiffness, and function scores (P<0.05). No adverse events were reported. Conclusions: Women with AI-induced arthralgias treated with acupuncture had significant improvement of joint pain and stiffness, which was not seen with sham acupuncture. Acupuncture is an effective and well-tolerated strategy for managing this common treatment-related side effect. [Table: see text] No significant financial relationships to disclose.
Gene expression profiling and copy number analysis to identify predictive molecular markers in breast cancer: Successful use of formalin fixed paraffin embedded tissue (FFPE)
Authors: Iddawela M. Y. , Wang Y. , Russell R. , Cowley G. , El-Sheemy M. , Eremin J. , Eremin O. , Faham M. , Earl H. M. , Caldas C. 
Published: August 2020

574 Background: FFPE is a valuable and widely available resource for translational research which to date has been under-used due to technical limitations. Improvement in technology has enabled genome-wide analysis of FFPE samples. We have assessed gene expression and copy number changes in the same cohort of breast cancers to identify markers or pathways important in prediction of treatment response. Methods: FFPE tissues from patients treated with neoadjuvant adriamycin/cyclophosphamide followed by taxanes in a clinical study were used. Gene expression profiling was assessed using the cDNA mediated annealing selection and ligation assay using the cancer panel which assess 502 genes (DASL assay, Illumina). Data was analysed using BeadStudio software. Copy number changes were assessed using the Molecular inversion probe assay with the 50K SNP panel (Affymetrix, California) and analysed using Nexus software (Biodiscovery). Results: Gene expression profiling was carried out on 44 samples. 12/44 (27%) patients had a pathological complete response (pCR) following chemotherapy. Significant differential expression of genes between pCR and non-pCR cancers were shown. TNFRSF5, CTSD, BCL3, ARNT, BIRC3, TGFBR1, MLLT6, and EVI2A were over-expressed and COL18A1, FGF12, IGFBP1 and NOTCH4 which were down-regulated in cancers that have a pCR (p ≤ 0.01). Copy number changes were assessed in 33 samples and comparison of copy number changes in pCR vs. non-pCR showed gains in regions 6q22, 21q21, 4p14, 4q21, 4p14, and loss at 11q11 (p ≤ 0.01). Three regions containing microRNA coding sequences, mir130a (11q11) mir142 (17q23) and mir21 (17q23) showed significant loss among pCR tumours (p < 0.05). Conclusions: This feasibility study shows that FFPE can be used for gene expression and copy number analysis which is a useful tool for the discovery of predictive markers for treatment response in neoadjuvant treatment trials. The role of TNFRSF5, microRNA 21/130a/142, and 11q11 loss should be further investigated as predictive markers of response to chemotherapy. [Table: see text]
Number needed to treat (NNT) to compare benefits of letrozole (LET) with adjuvant chemotherapy (CT) in patients (pts) with node-positive (N+) breast cancer (BC)
Authors: Dhillon N. , Kaura S. , Dranitsaris G. , Rugo H. 
Published: August 2020

581 Background: Adjuvant CT is an accepted treatment for N+ BC. The addition of taxanes to anthracycline based adjuvant CT has been demonstrated to improve overall survival (OS) in all but one study as in table below. BIG 1–98 has reported a survival gain with the aromatase inhibitor LET compared to tamoxifen (TAM). NNT (the reciprocal of absolute benefit) is the number of pts that need to be treated with a new intervention to avoid 1 additional event over the benefit provided by standard therapy. For multiple numerical outcomes from randomized trials, NNT is an effective method to express results in a clinically meaningful way. To evaluate the degree of benefit of LET over TAM in women with early stage N+ BC in BIG 1–98, we compared the NNT for survival benefit from LET to that needed to see benefit from the addition of a taxane to anthracycline based CT based on clinical trial data in BC pts with N+ disease. Methods: 5-yr survival data were taken from the pivotal randomized controlled trial (RCT) for LET (N+ pts from BIG 1–98, TAM arm censored for crossover to LET) and from 4 RCTs of adjuvant CT trials, AC-T, FEC-D, and DAC. NNT was calculated with respect to OS at 5 yrs; outcome is presented as the NNT to save a life (see Table). Results: The NNT to save a life for adjuvant LET vs TAM is comparable to the NNT for the addition of a taxane to anthracycline based CT in women with N+ BC. Conclusions: The magnitude of survival benefit of LET over TAM in terms of NNT is comparable to that needed to see a survival benefit from paradigm- changing modern adjuvant CT regimens. F= fluorouracil, E = epirubicin, C = cyclophosphamide, D = docetaxel, T = paclitaxel, A = doxorubicin [Table: see text] [Table: see text]
Effect of aprepitant (AP) on cyclophosphamide (CPA) pharmacokinetics (PK) in early breast cancer patients
Authors: Walko C. M. , Yu Y. A. , Bhushan S. , Spasojevic I. , Carey L. , Collichio F. , Armstrong D. , Dees E. C. 
Published: August 2020

588 Background: AP, a moderate inhibitor of CYP3A4, is a selective neurokinin 1 receptor antagonist recommended by the ASCO guidelines for prevention of high and some moderately emetogenic chemotherapy regimens, including doxorubicin and CPA (AC). CPA is converted to the active 4-OH metabolite primarily by CYP2B6 (48–57%) and by CYP3A4 (12–18%). CYP3A4 also converts 10% of CPA to the N-dechloroethyl metabolite (DCE), which is responsible for neurotoxicity and nephrotoxicity. Because AP is utilized concurrently with CPA, this creates the potential for drug-drug interaction between AP and CPA. The objective of this study was to evaluate the effect of AP on the PK of CPA, 4-OH, and DCE in patients receiving AC. Methods: This double-blinded, placebo controlled, two-period, crossover study included breast cancer patients receiving regimens containing CPA 600 mg/m2 IV for at least two sequential cycles. Prior to each CPA cycle, patients were randomized to receive either oral AP (125 mg on d 1 prior to chemotherapy and 80 mg on d 2 and 3) or placebo for 3 d. During both cycles, patients were also pretreated with ondansetron 24 mg PO and dex 12 mg PO on d 1 and dex 8 mg PO once on d 2 and 3. Rescue anti-emetic medications were permitted. Serial plasma samples were obtained from 0 to 24 h after administration of CPA in combination with AP or placebo in each patient. CPA, 4-OH, and DCE plasma concentrations were determined using HPLC. Area under the plasma versus conc time curve (AUC) was calculated using WinNonlin. Results: 17 patients completed 2 cycles and were evaluated for PK. Geometric mean AUC data for CPA in combination with AP and placebo are summarized in the table. Conclusions: Based on geometric mean ratios ± 90% CI, concurrent administration of AP with CPA did not result in any significant changes in the 4-OH metabolite AUC, but did result in increased parent CPA and decreased DCE drug exposure levels. Based on these results, it is unlikely that aprepitant has a clinically significant effect on the efficacy of CPA. [Table: see text] [Table: see text]
Dose-dense (DD) cyclophosphamide, methotrexate, and fluorouracil (CMF) at 14-day intervals: A pilot study of every 14- and 10–11-day dosing intervals for women with early-stage breast cancer
Authors: Drullinsky P. , Fornier M. N. , Sugarman S. , D'Andrea G. , Troso-Sandoval T. , Seidman A. D. , Yuan J. , Patil S. , Norton L. , Hudis C. 
Published: August 2020

590 Background: CMF (C 600 mg/m2, M 40 mg/m2, F 600 mg/m2) is an option for adjuvant therapy for patients with low risk early stage breast cancer. DD regimens as predicted by mathematical models of cancer growth and treatment response are superior. We previously demonstrated the safety of DD EC (epirubicin/cyclophosphamide) followed by paclitaxel at 10–11 day (d) intervals. We investigated the feasibility of administering DD adjuvant CMF every 14 d and then every 10–11 d in a 2-stage phase II trial. Methods: An initial cohort (A) was treated q 14 d with PEG-filgrastim (Neulasta) support. A second cohort (B) was treated every 10–11 d with filgrastim/Neupogen x 5 d and then, based on feasibility, modified (cohort C) to use 7 d filgrastim. The primary end point was feasibility defined as having ANC > 1.5 x 103/uL on day 1 of planned treatment for all 8 cycles with no grade 3 or higher non-hematologic toxicity. All three cohorts were tested using a Simon's two-stage optimal design with type I and type II errors set at 10%. This design would effectively discriminate between true tolerability (as protocol-defined) rates of< 60% and> 80%. Cohort A: 38 pts with early stage breast cancer were accrued from 3/2008 though 6/2008. Cohort B: 7 pts were accrued from June 2008 through August 2008. Cohort C: Is still open with 16 pts accrued from August 2008 through December 5, 2008. Results: Median age 51: range 38 to 78. Cohort A: 29/38 pts completed 8 cycles of CMF. The regimen was considered feasible. 2 other pts completed 7 cycles and were withdrawn for depression and grade 2 transaminitis. The 7 other pts completed between 1 and 6 cycles of CMF were withdrawn as follows: 3 personal, 1 (grade 3) bone pain, 2 allergy unrelated to CMF, and 1 seizure. Cohort B: 7 pts were accrued. 6 out of 7 pts could not complete 8 cycles of chemotherapy secondary to neutropenia and 1 secondary to grade 3 ALT elevation. Cohort C: Accrual has not been completed. 16 pts are currently enrolled. Conclusions: Dose dense adjuvant CMF is feasible at 14 d intervals with PEG-filgrastim support. Adjuvant CMF every 10–11 days with filgrastim given for 5 days beginning day 2 is not feasible. Accrual is ongoing for CMF at 10–11 days with filgrastim x 7 days. Updated results will be available for Cohort C. [Table: see text]