tbuckley/cabot-search huggingface dataset:
Reporting and Guidelines in Propensity Score Analysis: A Systematic Review of Cancer and Cancer Surgical Studies
Authors: Xiaoxin I. Yao, Xiaofei Wang, Paul J. Speicher, E. Shelley Hwang, Perry Cheng, David H. Harpole, Mark F. Berry, Deborah Schrag, Herbert H. Pang
Journal: JNCI Journal of the National Cancer Institute (2017)

Background: Propensity score (PS) analysis is increasingly being used in observational studies, especially in some cancer studies where random assignment is not feasible. This systematic review evaluates the use and reporting quality of PS analysis in oncology studies. Methods: We searched PubMed to identify the use of PS methods in cancer studies (CS) and cancer surgical studies (CSS) in major medical, cancer, and surgical journals over time and critically evaluated 33 CS published in top medical and cancer journals in 2014 and 2015 and 306 CSS published up to November 26, 2015, without earlier date limits. The quality of reporting in PS analysis was evaluated. It was also compared over time and among journals with differing impact factors. All statistical tests were two-sided. Results: More than 50% of the publications with PS analysis from the past decade occurred within the past two years. Of the studies critically evaluated, a considerable proportion did not clearly provide the variables used to estimate PS (CS 12.1%, CSS 8.8%), incorrectly included non baseline variables (CS 3.4%, CSS 9.3%), neglected the comparison of baseline characteristics (CS 21.9%, CSS 15.6%), or did not report the matching algorithm utilized (CS 19.0%, CSS 36.1%). In CSS, the reporting of the matching algorithm improved in 2014 and 2015 (P = .04), and the reporting of variables used to estimate PS was better in top surgery journals (P = .008). However, there were no statistically significant differences for the inclusion of non baseline variables and reporting of comparability of baseline characteristics. Conclusions: The use of PS in cancer studies has dramatically increased recently, but there is substantial room for improvement in the quality of reporting even in top journals. Herein we have proposed reporting guidelines for PS analyses that are broadly applicable to different areas of medical research that will allow better evaluation and comparison across studies applying this approach.
Concordance between upper and lower airway microbiota in infants with cystic fibrosis
Authors: Sabine M.P.J. Prevaes, Wouter A.A. de Steenhuijsen Piters, Karin M. de Winter-de Groot, Hettie M. Janssens, Gerdien A. Tramper-Stranders, Mei Ling J.N. Chu, Harm A. Tiddens, Mireille van Westreenen, Cornelis K. van der Ent, Elisabeth A.M. Sanders, Debby Bogaert
Journal: European Respiratory Journal (2017)

Nasopharyngeal and oropharyngeal samples are commonly used to direct therapy for lower respiratory tract infections in non-expectorating infants with cystic fibrosis (CF). We aimed to investigate the concordance between the bacterial community compositions of 25 sets of nasopharyngeal, oropharyngeal and bronchoalveolar lavage (BAL) samples from 17 infants with CF aged ∼5 months (n=13) and ∼12 months (n=12) using conventional culturing and 16S-rRNA sequencing. Clustering analyses demonstrated that BAL microbiota profiles were in general characterised by a mixture of oral and nasopharyngeal bacteria, including commensals like Streptococcus , Neisseria , Veillonella and Rothia spp. and potential pathogens like Staphylococcus aureus , Haemophilus influenzae and Moraxella spp. Within each individual, however, the degree of concordance differed between microbiota of both upper respiratory tract niches and the corresponding BAL. The inconsistent intra-individual concordance between microbiota of the upper and lower respiratory niches suggests that the lungs of infants with CF may have their own microbiome that seems seeded by, but is not identical to, the upper respiratory tract microbiome.
Treatment-related amenorrhea among young women one year following diagnosis of early-stage breast cancer.
Authors: Philip Daniel Poorvu, Shari I. Gelber, Shoshana M. Rosenberg, Rulla M. Tamimi, Kathryn Jean Ruddy, Sharon L Bober, Virginia F. Borges, Steven E. Come, Lidia Schapira, Ann H. Partridge
Journal: Journal of Clinical Oncology (2015)

9523 Background: Treatment-related amenorrhea (TRA) is common among premenopausal women treated for early-stage breast cancer and is associated with important reproductive, sexual, and metabolic side effects. Few prior studies have prospectively evaluated factors associated with TRA among young women receiving modern treatment regimens. Methods: As part of a prospective cohort study of women age ≤ 40 diagnosed with breast cancer, participants were surveyed at enrollment and one year following diagnosis (dx) regarding sociodemographics, medical history, menstrual status, and treatment. TRA at one year was defined as the absence of menses within the six months prior. Participants with stage IV disease or on ovarian suppression were excluded from this analysis. Univariable and multivariable modeling were used to determine demographic and treatment factors associated with TRA. Results: Among the 504 women included, 38% were age ≤ 35. Overall, 31% experienced TRA (Table 1). Univariable analysis revealed that TRA was associated with age, tamoxifen (TAM) use, and chemotherapy, but not race, BMI, smoking, co-morbidity (Charlson), or weight change since dx. Multivariable modeling revealed that relative to women age 36-40, women age 21-30 experienced significantly less TRA (OR 0.18, p < 0.0001). This difference was not statistically significant between women age 31-35 and women age 36-40 (OR 0.67, p = 0.09). TAM use (OR 1.97, p = 0.0002) and chemotherapy (OR 3.89, p < 0.0001) were also independent predictors of TRA. Effects of different modern regimens on TRA in this young cohort will be presented. Conclusions: This analysis represents the largest evaluation to date of very young women and confirms that older age and treatment with TAM and chemotherapy are predictors of TRA. Further research to identify differences in short and long-term risk of TRA with modern treatment, including specific chemotherapy regimens, is warranted. No TRA TRA Age (years) 21-30 n (%) 59 (88) 8 (11) 31-35 n (%) 88 (70) 38 (30) 36-40 n (%) 200 (64) 111 (36) Tamoxifen No n (%) 144 (77) 44 (23) Yes n (%) 203 (64) 113 (36) Chemotherapy No n (%) 136 (76) 26 (24) Yes n (%) 211 (62) 131 (38) Total n (%) 347 (69) 157 (31) Key: TRA (Treatment-related amenorrhea).
Ipilimumab: First results of a phase I trial in pediatric patients with advanced solid tumors.
Authors: Melinda S. Merchant, Kristin Baird, Leonard H. Wexler, Carlos Rodriguez-Galindo, Crystal Mackall
Journal: Journal of Clinical Oncology (2012)

9545 Background: Ipilimumab is a fully-human IgG1 monoclonal anti-CTLA-4 antibody which has been approved by the FDA for adult patients with metastatic melanoma . Although the approved dose is 3mg/kg every 21 days, the dose of 10mg/kg IV every 21 days for 4 doses in combination with chemotherapy was well tolerated in a phase III trial enrolling adult patients with melanoma. Methods: This pediatric phase I, dose escalation study examined the safety, tolerability, pharmacokinetics, and immunogenicity of ipilimumab administered to patients &lt;21yo with recurrent or progressive solid tumors. Ipilimumab was administered at 1, 3, 5, and 10mg/kg IV in a standard 3 + 3 design with 4 doses of induction therapy q3 weeks followed by maintenance q3 months until disease progression or unacceptable toxicity. Tumors were measured after 6 weeks, 12 weeks, and then every 3 months. Results: Twenty one patients (melanoma n=6, osteosarcoma n=6, soft tissue sarcomas n=7, neuroblastoma, and renal cell carcinoma) received a total of 57 doses of Ipilimumab to date. One of 6 patients treated at 5mg/kg developed a dose-limiting grade 3 pancreatitis. .At the highest dose level of 10mg/kg, two of three patients under 12yo developed DLT: grade 3 colitis and concurrent norovirus in one patient, and self-resolving grade 3 transaminitis in a second patient. Three of three patients between the ages of 12 and 21yo tolerated the 10mg/kg dosing schedule without DLT. Across all dose levels, grade 2 or 3 adverse events included colitis (n=1), transaminitis (n=3), pancreatitis (n=1), autoimmune thyroiditis (n=2), and hypophysitis (n=1) observed between C1D8 and C4D21. A single grade 1 rash was observed. Stable disease was the best response in 5 patients with a duration of 3 to 18 months. Conclusions: Ipilimumab can be safely administered to pediatric patients. Adolescents are able to tolerate the highest dose of 10mg/kg. Younger children (&lt;12yo) had 2 DLTs in 3 patients at 10 mg/kg . Expansion of the 10 mg/kg cohort for adolescents and of the 5 mg/kg dose for the &lt;12yo for further safety and pharmacokinetic information is underway. The spectrum of adverse events appears similar to those described in the adult trials, although there were no grade 2 or higher incidents of rash.
MAGIC germline polymorphism analysis.
Authors: Elizabeth Catherine Smyth, Shenli Zhang, David Cunningham, Iain B. Tan, Andrew Wotherspoon, Richie Soong, Nur Sabrina Binte Sapari, Alicia Frances Clare Okines, Ruth E. Langley, Sally Patricia Stenning, Matthew Guy Nankivell, Patrick Tan
Journal: Journal of Clinical Oncology (2014)

4068 Background: Germline polymorphisms may affect chemotherapy efficacy and survival. We examined the effect of polymorphisms in drug metabolism and DNA repair genes on survival for patients (pts) randomised to surgery alone or perioperative ECF chemotherapy in the MRC MAGIC trial. Methods: DNA was extracted from nontumor resection FFPE blocks. ERCC1, ERCC2, XRCC1, DYPD, and OPRT SNPs were evaluated using Sequenom, GSTP1, GSTT1 deletion and TS 5’ 2R/3R using multiplex PCR. Post PCR amplification TS 2R/3R and GSTT1 samples underwent gel electrophoresis. Results: Results are available on 289/456 resected pts. Duplicate pair concordance with Sequenom was excellent (98%). Discrepancy was significant for duplicate pairs analysed for 5’ TS 2R/3R and GSTT1 length based polymorphisms; these were not analysed further. For genotype frequency and survival see Table. There was no evidence of an interaction between any genotype and treatment. Conclusions: No polymorphism examined was predictive of survival in MAGIC. SNP analyses from FFPE are reproducible but due to DNA fragmentation length based polymorphisms may not be; results from such studies should be interpreted with caution. Gene SNP Genotype and Frequency Effect of genotype on OS: Median OS (y) from surgery XX XY YY Surgery Chemo + Surgery OPRT G638C (Gly213Ala) GG 64% GC 33% CC *3% GG 2.09 (ref) GC 1.68; HR 1.01, p=0.963 GG 1.83 (ref) GC 2.86; HR 0.74, p=0.263 ERCC1 C118T CC 17% CT 48% TT 35% CC 2.83 (ref) CT 1.71; HR 1.08, p=0.764 TT 1.59; HR 1.17, p=0.577 CC 1.36 (ref) CT 1.71; HR 0.99,p=0.973 TT 3.54; HR 0.68, p=0.286 ERCC1 C8092A TT *6% GT 43% GG 51% GG 1.69 (ref) GT 1.76; HR 0.97, p=0.879 GG 2.36 (ref) GT 2.13; HR 1.05, p=0.832 ERCC2 Lys751Gln GG 15% GT 44% TT 41% GG 1.51 (ref) GT 3.27; HR 0.80, p=0.5 TT 1.57; HR 1.21, p=0.548 GG 1.28 (ref) GT 2.86; HR 0.57, p=0.066 TT 1.71; HR 0.69, p=0.223 XRCC1 A399G AA 13% AG 43% GG 44% AA 0.8 (ref) AG 1.85; HR 0.68, p=0.24 GG 2.6; HR 0.63, p=0.156 AA 0.98 (ref) AG 1.94; HR 0.72,p=0.323 GG 2.46; HR 0.7, p=0.288 GSTP1 I105V AA 51% AG 41% GG 8% AA 2.11 (ref) AG 1.59; HR 1.19, p=0.416 AA 1.89 (ref) AG 2.82; HR 0.84, p=0.478 DPYD A1627G AA 69% AG 26% GG *6% AA 2.31 (ref) AG 1.28; HR 1.75 p=0.008 AA 2.82 (ref) AG 1.60; HR 1.23, p=0.371 DPYD IVS14+1G>A GG >99% GA *<1% AA *0% No analysis due to low % GA/AA genotypes * Genotypes ≤ 8% frequency not analysed for OS.
Experience with a nurse navigator-led, risk-based breast cancer survivorship care clinic.
Authors: Julie Ellis, Nayana Dekhne, Angela DeLaere, Blerina Pople
Journal: Journal of Clinical Oncology (2017)

52 Background: Our tertiary care hospital addressed recent survivorship care initiatives by implementing a Nurse Practitioner (NP)-led Breast Care Survivorship Clinic (BCSC). The monthly, NP-led multidisciplinary clinic (MDC) integrated the unique needs of Breast Cancer Survivors (BCS). After 14 months, an internal evaluation prompted three significant changes to the NP-led BCSC. First, the new BCBS would become a Nurse Navigator (NN)-led risk-based model that would allow survivorship care to be individually tailored to each BCS’s needs. Secondly, patients would not meet with rest of MDC team (i.e. social work, nutrition, physical therapy) during this visit. Patients were instead referred to the Survivorship Care Workshop Series (SCWS), a bi-monthly educational program developed to complement the NN-led BCSC and address common BCS needs; needs falling outside of the SCWS content were handled individually by MDC referrals. Lastly, the NN-led BCSC was conducted at follow-up visit with surgeon to avoid an additional appointment. The NN administers a questionnaire that addresses medical and psychosocial concerns, refers BCS to relevant SCWS lecture and/or MDC referrals based on questionnaire results, and finally, delivers the SCP. Methods: A comparison of the NP-led versus the NN-led BCSC was performed on the following factors: average total time and effort (T&amp;E) for preparation and delivery of SCPs; number of actual SCPs delivered to BCS; and cost analysis of each model. Results: There were 58 SCPs completed, and 37/58 were successfully delivered to patients during the NP-led BCSC (9/2014-10/2015). There were 95 SCPs completed, and 91/95 were successfully delivered during the NN-led BCSC (2/2016-7/2016). The average total time spent by NP was two hours (n = 37) per patient compared to the average total time of 45 minutes spent by NN (n = 91) for preparation and delivery of SCPs. The estimated annual cost of the NP-led model includes T&amp;E for NP and MDC team, is $273,946 compared to cost of the NN-model, which includes NN T&amp;E as well a full-time SCWS program coordinator, is $86,651. Conclusions: The NN-led risked-based BCSC model is less resource-intensive, less expensive and allows for increased delivery of SCPs to BCS.
Pelvic exenterations for gynecologic malignancies: 20-year experience at a cancer institute
Authors: S. Sharma, K. Odunsi, S. Lele
Journal: Journal of Clinical Oncology (2004)

5138 Background: Pelvic exenterations have undergone multiple modifications since originally described 55 years ago. Most common indication is centrally recurrent or persistent cancer of the cervix after radiation therapy. The goal of this study is to retrospectively review gynecologic patients that have undergone pelvic exenterations at a single cancer institution. Methods: All women that underwent a pelvic exenteration for a gynecologic malignancy between January 1980 and December 1999 were reviewed. 48 patients were reviewed by organ, histology, stage and type of exenteration. Outcomes reviewed were the early and late postoperative complications (< 30 or > 30 days of surgery), need for reoperation, recurrence of tumor, survival, disease free interval, and life after pelvic exenteration. Variables were analyzed by the log-rank test and Kaplan-Meier curves. Results: 48 patients (ages 21–78) underwent pelvic exenterations for cervical (39), vulvar (3), endometrial (2), ovarian (2), and vaginal (2) cancers. 41 underwent total exenteration, 6 anterior, and 1 posterior. Majority of patients (45) had received prior radiation therapy. The median survival was 35 months and the disease free survival was 32 months. Mortality from the procedure was 4.2%. Early and late postoperative complication rates were 27% and 75% respectively. Recurrence rate was 48%; majority of recurrences were in the pelvis (50%). 8 patients received intraoperative radiation. Univariate analysis failed to show an association between type of pelvic exenteration, type of fecal and urinary diversion, outcome, need for reoperation, and recurrence. Conclusions: Contemporary pelvic exenterations are associated with a low mortality and potential for long-term survival in a subset of patients that historically have been given a poor prognosis. In patients with recurrent gynecological cancer confined centrally to the pelvis, pelvic exenteration still remains the choice of therapy as response to chemotherapy to a centrally recurrent tumor in radiated area continues to be poor. Intra-operative radiation in select few patients needs to be further studied. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GlaxoSmithKline
Novel urine markers for diagnosing and monitoring non-indolent prostate cancer.
Authors: Daniella Bianchi-Frias, Ilsa Coleman, John Samuel Banerji, Khanh Ngoc Pham, Claudio Jeldres, Roman Gulati, Jing Xia, Scott A. Tomlins, Christopher R. Porter, Peter Nelson
Journal: Journal of Clinical Oncology (2015)

e16113 Background: Prostate cancer (PCa) is the most common solid tumor in men. Active surveillance (AS) is an acceptable alternative to immediate treatment for low-risk PCa. However, AS often entails significant risk of under-grading the tumor and repeated invasive biopsies. We hypothesized that transcripts associated with high Gleason grade cancers are quantifiable in urine samples and reflect the presence of higher-grade non-indolent tumors.Our objective was to develop a qPCR-urine-based assay for the detection of occult high-grade cancer in urine samples from PCa patients. Methods: By comparing transcriptional profiles of Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancers, we identified transcripts differentially expressed between these histologies. Four consistently up-regulated GP4 transcripts (RELN, GRIN3A, RGS5 and LRNN1) were evaluated in RNA extracted from urine sediments from 53 PCa patients. Urine specimens were obtained following a vigorous digital rectal exam and immediately prior to radical prostatectomy. qPCR was performed for the GP4 markers and normalized to KLK3 and RPL13A. To evaluate the ability of the GP4 markers to discriminate between low- and high-grade tumors, univariate and multivariate logistic regression analyses were performed and the overall significance determined using likelihood ratio tests. Results: When tested as individual variables, each gene was an independent predictor of high-grade (Gleason score ≥ 4+3 vs. ≤ 3+4) prostate cancer (p < 0.05 for each gene) with area under receiver operating characteristic curves (AUC) ranging from 0.770 to 0.794. When tested as a panel, the 4 genes were significantly associated with high-grade cancer based on the overall likelihood ratio test (p = 0.002). Furthermore, the 4-gene panel outperformed each gene alone, with an AUC of 0.841. Conclusions: A novel 4-gene panel assayed by qPCR appears to be capable of discriminating clinically relevant high-grade (Gleason ≥ 4+3) tumors from low-grade (Gleason ≤ 3+4) tumors using urine sediments. Further studies are needed to confirm these preliminary findings.
A randomized phase II study to investigate the deepness of response (DpR) of FOLFOXIRI plus cetuximab (Erbitux) versus FOLFOXIRI plus bevacizumab as the first-line therapy in metastatic colorectal cancer (mCRC) patients with RAS wild-type tumors: DEEPER.
Authors: Akihito Tsuji, Yu Sunakawa, Wataru Ichikawa, Yutaro Kubota, Mitsugu Kochi, Takashi Sekikawa, Tamotsu Sagawa, Masahito Kotaka, Masato Nakamura, Ken Shimada, Toshiki Masuishi, Hironaga Satake, Taichi Yabuno, Taichi Yoshida, Masahiro Goto, Hirofumi Ota, Yoshihiro Okita, Masahiro Takeuchi, Masashi Fujii, Toshifusa Nakajima
Journal: Journal of Clinical Oncology (2017)

TPS818 Background: The FIRE-3 study proved that early tumor shrinkage (ETS) and DpR were superior with FOLFIRI plus cetuximab (cet) compared to bevacizumab (bev) in mCRC patients with RAS wild-type tumors (Stintzing S, et al. Lancet Oncol 2016). A retrospective analysis of treatment groups between FOLFOXIRI plus anti-EGFR antibody and bev showed significantly better DpR and ETS in the anti-EGFR antibody group (48.6% vs. 37.8% for the median DpR; 40.8% vs. 26.4% for the median ETS)(Salvatore L, et al. ESMO 2014). However, there have been few studies comparing cet with bev in combination with the FOLFOXIRI regimen used as a platform. Therefore, it is great interest to investigate whether cet will be more beneficial than bev when combined with the triplet regimen as a promising treatment option. Methods: Key eligibility criteria are as follows: histologically proven unresectable metastatic/recurrent CRC; RAS wild-type tumors; patients who have not received any prior chemotherapies or patients with relapse after at least 12 months following adjuvant chemotherapy. Primary endpoint of this study is the DpR until progression. Key secondary endpoints are the ETS at Week 8, progression-free survival, overall survival, and safety. After randomization, patients receive up to 12 cycles of FOLFOXIRI (irinotecan: 150 mg/m 2 , oxaliplatin: 85 mg/m 2 , l-levofolinate: 200 mg/m 2 , continuous fluorouracil: 2400 mg/m 2 , every two weeks) plus cet (initial: 400 mg/m 2 , subsequent: 250 mg/m 2 , weekly) or bev (5 mg/kg, every two weeks) as induction treatment. Thereafter, fluorouracil, l-levofolinate, and cet or bev are administrated as maintenance treatment. Based on previous reports, the difference of 12.5% in the median DpR between the cet and bev groups was assumed. Each standard deviation was estimated to be 42% (cet group) and 34% (bev group). Under the conditions of significance level of 0.05 for a two-sided test and power of 0.85, the required sample size was calculated to be 360 patients. Thirty-three patients have been enrolled by August 2016. Clinical trial information: 000018217.
Community use of anthracyclines for adjuvant HER2-positive breast cancer (BC).
Authors: Akhil Kumar, Marc L. Fishman, William S. Shimp, Laura Rose Bobolts, James Edward Krook, Val Fishman, Sharon Davis, Dinah Huff, Carol Anthony, Robert Walton, William J. Hrushesky
Journal: Journal of Clinical Oncology (2013)

e11609 Background: Anthracyclines remain among the most active agents for the treatment of BC. NSABP B-31, NCCTG N9831 and HERA, each employing anthracyclines followed by trastuzumab in adjuvant HER2+ BC, demonstrated significant reduction in the risk of recurrence and improvement in survival . A fourth study, BCIRG-006, compared a non-anthracycline containing regimen, TCH, to an anthracycline based regimen, AC-TH . Both arms had similar overall survival, but there was a higher incidence of cardiac events in patients who received anthracycline. HER2-analyses in randomized adjuvant trials, in the pre-trastuzumab era, comparing anthracycline with non-anthracycline chemotherapy regimens, show that HER2+ BC derives greater benefit from anthracycline use . TOP2A coamplification, which occurs in 35% of HER2-positive patients, has shown a direct association with anthracycline benefit in several studies. We investigate and report, herein, the ways in which community oncologists are currently treating these patients. Methods: All treatment requests for adjuvant trastuzumab were examined, from 2009 through 2012. Chi-square analysis at 0.05α was used to test for interaction of age group to type of treatment. Results: During this span, oncologists requested adjuvant trastuzumab for 121 patients. In 10% (12/121) of patients, adjuvant trastuzumab alone, without chemotherapy and with or without hormonal therapy, was requested. Among patients who also received adjuvant chemotherapy (109), 35% (38/109), received anthracyclines. There was no relationship of anthracycline-usage with BC stage (data not shown) or patient age (Chi Sq p = 0.73). Adjuvant trastuzumab, without chemotherapy, was requested more often for the elderly (20% versus 4%; Chi Sq p = 0.003). Conclusions: Anthracyclines are utilized in adjuvant HER2+ BC in only about a third of patients, regardless of BC stage or patient age. The availability of a reliable, inexpensive, and convenient test to predict which patients are most likely to benefit from anthracyclines, over other options, would be useful. [Table: see text]