bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of clinical outcomes with IMRT and proton therapy for prostate cancer.
Authors: Mendenhall Nancy P. , Wong William , Bryant Curtis , Vora Sujay A. , Henderson Randal H. , Keole Sameer R. , Hoppe Bradford S. , Vargas Carlos E. , Nichols R. Charles , Daniels Thomas Backus , Mendenhall William M. , Morris Christopher G. , Schild Steven E. 
Published: September 2018

e16555 Background: The ProtecT trial underscores the importance of treatment in men with prostate cancer and life expectancies > 10 years and the validity of radiation therapy (RT). RT can be given with photons or protons (PT). To address the controversy of which is better, clinical outcomes of photon-based intensity modulated RT (IMRT) and PT cohorts from 2 institutions were directly compared. Methods: Under respective IRB approvals, data from 2 cohorts were analyzed. The first was 301 men treated with ultrasound image guided IMRT from 2000-05 to 75.6 Gy in 42 fractions. The second was 1214 men treated with fiducial image guided PT from 2006-10 to 78 CGE in 39 fractions. Median age and followup were 74 y and 7.2 y for IMRT and 66 y and 5.6 y for PT. Hormone therapy (ADT) was used with IMRT and PT, respectively, in 3% and 7% of low-risk patients, 25% and 9.9% of intermediate-risk, and 91% and 57.8% of high-risk. Comparative endpoints were age-stratified 5-year (5Y) survival (OS), ≥ grade 3 gastrointestinal (GI) and urologic (GU) toxicity, and 5Y freedom from biochemical progression (FFBP). Results: There was a lower prevalence of GI (1.3% vs 0.1%, p = 0.0065) and GU (4.3% vs 0.1%, p < 0.0001) toxicity at last follow-up in the PT group. In the IMRT and PT cohorts, OS rates were 90.8% and 88.7% in men ≥75 (p = 0.4083). In men < 75, OS rates were 91.6% and 97.5% in the IMRT and PT low-risk patients (p = 0.003), 92.1% and 95.5% in the IMRT and PT intermediate-risk (p = 0.0535), and 92.0% and 90.0% (p = 0.4975) in the IMRT and PT high-risk. In the IMRT and PT cohorts, respectively, FFBP rates were 92.2% and 98.9% for low-risk patients (p < 0.0001), 87.3% and 94.5% for intermediate-risk patients(p = 0.0226), and 80.3% and 74.4% for high-risk patients (p = 0.5154). Conclusions: In this retrospective comparison of outcomes in cohorts of men treated with IMRT and PT for prostate cancer, FFBP rates were better with PT for men with low- and intermediate-risk disease and similar in men with high-risk disease despite longer and more frequent use of ADT in the IMRT cohort. This study underscores the difficulty of comparing retrospective series, with differences noted in age, RT dose, and ADT use between cohorts. However, the magnitude of improvement with PT is intriguing and warrants prospective testing.
A signature of miRNAs in the blood to help prognosticate prostate cancer at the time of diagnosis.
Authors: Sita-Lumsden Ailsa Roberg , Leach Damien , Zivi Andrea , Winkler Mathias , Waxman Jonathan , Bevan Charlotte 
Published: September 2018

e16558 Background: Prostate cancer (PCa) is the most commonly diagnosed cancer in men. Around 80% of PCas are diagnosed as early, localised stage yet a subset of these will metastasise and eventually prove fatal. Management decisions are based on risk stratification systems. However, these systems are not able to clearly distinguish indolent from aggressive PCa’s and as a result many patients with indolent cancers may be over treated. Circulating microRNAs (miRNA) may be an easily accessible, suitable biomarker to distinguish true indolent from clinically significant early PCas thus reducing overtreatments. Methods: Blood samples from 24 men with benign prostatic hypertrophy (BPH, n = 8), localised PCa (n = 8) or metastatic PCa (n = 8) were collected at time of diagnosis. All men had intact prostates and were naïve to any endocrine or other cancer therapy. A platform of circulating miRNAs were analysed in serum using Abcam FireflyTM technology. Data collected were independently verified using real-time qPCR (Exiqon TM ). The miRNAs identified as being significantly different between groups were then analysed in a published dataset. Results: Serum levels of seven of the miRs examined were significantly different in patients with prostate cancer compared to control across both platforms (miR-10b, miR-125b, miR-210, miR-21, miR-378a, miR-483 and miR93 all with P values < 0.005). A further four miRNAs could differentiate between the benign and metastatic cohorts (miR-126 P = 0.008, miR-150 P = 0.05, miR375 P = 0.007). Kaplein-Meier analysis further identified that the serum levels of four miRNAs showed significant association with survival rates (miR-21 P = 0.032, miR-126 P = 0.032, miR-150 P = 0.032, miR-93 P = 0.019). On examination in a cohort of 280 men from The Cancer Genome Atlas (TCGA), four miRs from the cohort had significantly different expression in patients who eventually relapsed (miR-21 P = 0.048, miR-375 P = 0.021, miR-210 P = 0.0003, miR-93 P = 0.008) Conclusions: Our circulating miRNA based signature could be used to stratify men at prostate cancer diagnosis and help identify those who are likely to harbour micro metastases and would benefit more from an early radical treatment. The data is being validated in larger cohorts.
Insurance status and survival among prostate cancer patients: A population-based study.
Authors: Lu-Yao Grace L. , He Jianming , Kelly William Kevin , Delgado David J. , Gomella Leonard G. 
Published: September 2018

e16563 Background: This population-based study assesses the relationship between insurance status and survival outcomes among men with prostate cancer diagnosed before 65 years of age. Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 114,871 prostate cancer patients diagnosed before age 65 in 2007-2013. Insurance type was classified as uninsured, Medicaid, and other (including private insurance and coverage from the military or veterans affairs). Disease risk group was based on the NCCN criteria. We used multivariable Cox proportional hazards models to estimate the relative risks of all-cause mortality and prostate cancer specific mortality (PCSM), adjusted by age, race, marital status, region, diagnosis period, and primary treatment. Results: Compared with patients with other insurance, Medicaid and uninsured patients experienced 103% and 41% higher all-cause mortality. The corresponding increase for PCSM were 61% and 32%. Medicaid patients experienced 44% (HR=1.44, 95% 1.25-1.65) higher all-cause mortality than uninsured patients. Table 1 provides data stratified by risk status at diagnosis. Conclusions: Uninsured and Medicaid patients experienced higher PCSM and all-cause mortality compared to other insured patients across all disease severity. Medicaid patients experienced worse all-cause mortality compared with uninsured patients. Further studies are warranted to investigate factors related to poor survival outcomes among uninsured and Medicaid patients. [Table: see text]
PCA3 upregulation in prostate cancer: Analysis in a cohort of 497 subjects from TCGA.
Authors: Dias-Neto Emmanuel , Nunes Diana N. , Thomas Andrew M. , Smith Tracey L. , Rao Arpit , Lauer Richard C. , Chen Isan , Arap Wadih , Pasqualini Renata 
Published: September 2018

e16578 Background: Approved by the FDA as a diagnostic test, the long non-coding RNA PCA3 is the most specific human prostate cancer biomarker identified to date. The biological function of PCA3, which involves downregulating the tumor suppressor gene PRUNE2, has important therapeutic implications. Here we investigated RNA expression levels of these genes to better understand the dynamics of this regulatory process during cancer progression and its relevance for tumor aggressiveness. Methods: We downloaded clinical data, as well as PCA3 and PRUNE2 gene expression values (log2 RSEM), from 497 TCGA prostate cancer patients (totaling 550 samples) and their matched normal tissues using the Xena Browser. Expression values for both genes, and their ratios, were evaluated in terms of tumor vs non-tumor tissue, biochemical recurrence, pathologic T stage, Gleason scores and age at diagnosis. All p-values were obtained by the Wilcoxon rank Sum (2 groups) or the Kruskal-Wallis Test (3+ groups). Results: Using 52 malignant/non-malignant tissue pairs from our cohort, we confirmed previous findings that showed simultaneous PCA3 upregulation and PRUNE2 reduction in malignant samples when compared to non-malignant ( p<0.001). Normalized levels of PRUNE2 were informative for advanced tumors (Gleason >7) and in younger subjects (<50 years old), whereas PCA3/ PRUNE2ratios could discriminate all but the age at diagnosis group, and PCA3 levels were informative for all comparison groups. Conclusions: PCA3 appears to be a valuable marker of early stage disease or a less aggressive tumor. This suggests the activation of this oncogene to be an early event in PrCa, which may be later on replaced by other mechanisms that would sustain cancer progression and metastasis. [Table: see text]
Computer extracted shape features of prostate capsule from MRI to predict biochemical recurrence of prostate cancer post-treatment.
Authors: Ghose Soumya , Shiradkar Rakesh , Rusu Mirabela , Mitra Jhimli , Thawani Rajat , Gupta Amar , Purysko Andrei , Madabhushi Anant 
Published: September 2018

e16579 Background: Pre-treatment identification of biochemical recurrence (BCR) from MRI may enable the use of aggressive neo-adjuvant therapies for prostate cancer patients to improve prognosis. BCR is often associated with aggressive cancer growth and/or extra prostatic extension resulting in an irregular bulge and focal capsular retraction. This may induce differences in the shape of the prostate capsule between BCR positive (BCR+) and BCR negative (BCR-) patients as observed on MRI. In this work, we show that computer extracted shape features of the prostate capsule on MRI can identify patients that are at a risk of BCR post-treatment Methods: In a single centre IRB approved study, from a registry of 874 patients, availability of complete image datasets (T1w, T2w and ADC map); no treatment for PCa before MRI; presence of clinically localised PCa; availability of Gleason score; and data available for post-treatment PSA and follow-up for at least 3 years in patients without BCR were used as inclusion criteria to select 80 patients. The prostate capsule was manually segmented on T2w MRI by an experienced radiologist. Two atlases A+ and A- were created for BCR+ and BCR- patients respectively with similar Gleason score (6 to 9), similar numbers in each cohort (25 each) and similar tumor stage (T2 to T3). A t-test based analysis corrected for multiple comparison revealed statistically significant prostate shape differences between A+ and A- in surface of interest (SOI). Curvature features (magnitude and surface normal orientations) were extracted from SOI of the two cohorts. A random forest classifier was trained using the 50 training images (from A+ and A-) and validated using a hold-out validation set of 30 patients. Results: The inter-quartile range, variance, skewness and kurtosis of curvature magnitude and normal orientations were found to be predictive of BCR. The RF classifier trained using these features could predict BCR with an accuracy of 78% and an AUC of 0.71 in the validation set. Conclusions: Curvature magnitude and orientation features of the prostate capsule from the SOI may be predictive of BCR. In future a multi centre independent datasets will be used to validate the findings.
Early and late morbidity of radical hysterectomy with lymphadenectomy in early-stage cervical cancer: A prospective multicentric cohort of 232 patients.
Authors: Balaya Vincent , Rossi Léa , Ngo Charlotte , Bats Anne-Sophie , Mathevet Patrice , Lecuru Fabrice ,   SENTICOL Group
Published: September 2018

e17007 Background: The aim of this study was to assess the early and late post-operative morbidity of patients who have undergone a radical hysterectomy (RH) for early-stage cervical cancer. Methods: We retrospectively analyzed the data of two prospective trials on sentinel node biopsy for cervical cancer (SENTICOL I & II). Patients underwent a radical hysterectomy for early-stage cervical cancer between January 2005 and March 2012 in 23 French oncologic centers. Results: A total of 412 patients were enrolled and 284 had a radical hysterectomy. Data were complete for 232 patients: 115 by laparoscopic-assisted vaginal way, 80 patients by total laparoscopic way, 9 patients by total vaginal way, 22 patients by laparotomy and 6 patients by robot-assisted way. The median age was 44 years (range = 25-85 years). 89.6 % of patients had a stage IB1 disease. 72.4% were epidermoid carcinoma and 24.6% adenocarcinoma. Eighty-one patients (35%) had only a sentinel lymph node biopsy and 151 patients (65%) had an additional pelvic lymphadenectomy. There were 45 cases of urinary infections (19.4%), 17 cases of dysuria (7.3%), 10 cases of urinary incontinence (4.3%), and 6 cases of ureteral or vesical fistula (2.6%). The genito-femoral nerve was injured in 25 cases (10.7%) and the obturator nerve was injured in 22 cases (9.5%). There were 38 cases of limb lymphedema (16.3%) and 14 cases of pelvic lymphocyst (6%). Conclusions: These complications rates are similar with those found in the current literature. Urinary infections and limb lymphedema are the main complications of RH. The functional outcomes could be improved by applying nerve-sparing techniques. [Table: see text]
Diagnostic value of 18F-FDG PET/MRI for the detection of lymph node metastasis in gynecologic cancer.
Authors: Tsuyoshi Hideaki , Tsujikawa Tetsuya , Okazawa Hidehiko , Yoshida Yoshio 
Published: September 2018

e17014 Background: Integrated PET/MRI simultaneously provides the metabolic (PET) and functional (DWI) information. It may provide high diagnostic performance in gynecologic malignancies due to the excellent soft tissue contrast. However, up to the present date, only a few studies have shown the diagnostic value of PET/MRI in gynecologic cancer. The aim of our study was to clarify the diagnostic ability of PET/MRI for the detection of lymph node metastasis which can correlate to the prognosis of gynecologic cancer patients. Methods: Eighteen patients with a primary or a suspected recurrent gynecologic cancer (cervical, endometrial and ovarian cancer) were included. They underwent preoperative PET/MRI and CT scans. The morphological criterion on CT was based on the size of lymph nodes which was larger than 1.0 cm in the long axis. The PET criterion was based on the positivity which was higher 18F-FDG uptake compared with the surrounding tissue. On DWI, lymph node was defined as positive in the presence of higher signal intensity compared with the surrounding tissue. The presence or absence of lymph node metastasis was confirmed by surgical pathology. McNemar test was used for the comparison of the diagnostic ability of lymph node metastasis among PET, DWI and CT. Results: Lesion-based sensitivity, specificity and diagnostic accuracy were 23.8%, 96.9% and 84.0% for CT, 93.75%, 87.50% and 88.46% for DWI and 90.48%, 92.86% and 92.44% for PET. PET had a significantly higher sensitivity (P < 0.001) and a higher accuracy (P < 0.05) than CT for the detection of lymph node metastasis. PET also tended to have a higher specificity compared with DWI (P = 0.074). The combination of PET with DWI correctly detected 2 additional lesions to PET alone. Conclusions: Our results demonstrate that integrated PET/MRI can offer a high diagnostic value for the detection of lymph node metastasis in gyn ecologic cancer. The combination of PET with DWI may provide a higher diagnostic accuracy than two separate devices.
Identification of ideal strategy of cervical cancer screening in Japan based on Fukui cervical cancer screening study.
Authors: Kurokawa Tetsuji , Shinagawa Akiko , Chino Yoko , Kobayashi Motohiro , Yoshida Yoshio 
Published: September 2018

e17025 Background:The estimated age-standardized incidence rate for cervical cancer is higher in Japan than in North America and the UK. It is important to improve cancer screening. The introduction of HPV testing with cytology for triage of those that test positive for cervical cancer screening has been challenging. The Fukui Cervical Cancer Screening (FCCS) study was designed to determine the best cervical cancer screening method in the Japanese population. We performed a subanalysis using baseline data of FCCS study to determine the performance of cytology, the human papillomavirus (HPV) testing and cotesting with cytology and HPV testing, and to evaluate whether the stratification of HPV16, HPV18, and 12 other hrHPV types appropriately balances risks and harms in the Japanese cancer screening population. Methods:The study enrolled 7,584 women aged 25 years or older undergoing routine screening. All women underwent liquid-based cytology (LBC) and cobas HPV testing. Women with abnormal cytology regardless of the HPV status, women with positive hrHPV results regardless of cytology results, and women randomly selected from among those with normal cytology and negative hrHPV results were referred for colposcopy. Results:The prevalence of hrHPV, HPV16, and HPV18 was 6.8%, 1.2%, and 0.5%, respectively. The estimated sensitivities for cervical intraepithelial neoplasia (CIN) 2 or worse for cytology, HPV testing, and cotesting with cytology and HPV testing were 71%, 92%, and 100%, respectively. The estimated positive predictive values for cytology, HPV testing, and cotesting with cytology and HPV testing were 33%, 21% and 21%, respectively. Using a strategy whereby those with abnormal cytology or positive HPV16 genotype undergo colposcopy and biopsy results in a sensitivity of 85% and a positive predictive value of 33%. This strategy results in improved sensitivity while at the same time maintains the positive predictive value compared to screening with cytology alone. Conclusions:Baseline data from the FCCS study suggests that strategy of using colposcopy for women with abnormal cytology and/or HPV16 positivity appropriately balances risks and harms for Japanese women. Clinical trial information: UMIN000025977.
A first report of robotic-assisted sentinel lymph node mapping and inguinal lymph node dissection, using near-infared fluorescence, in vulvar cancer.
Authors: Hunter Mark , Kremer Kevin , Wymore Kristen 
Published: September 2018

e17027 Background: Vulvar carcinoma is a rare gynecologic malignancy which has seen a considerable evolution in surgical techniques over the last several decades. However, the morbidity associated with inguinal lymph node dissections remains significant. The majority of patients undergoing full lymphadenectomy will have some complication, with wound breakdown being the most common. In males, robotic inguinal lymph node dissection has been described for penile cancer. This report represents a first use of near-infared fluorescence for sentinel inguinal lymph node mapping, and the first description of complete robotic inguinal lymph node dissection for patients with vulvar malignancies. Methods: Bilateral robotic-assisted inguinal lymph node mapping and and lymphadenectomy was performed using the daVinci Xi system with a near-infared fluourescence. Results: The patient presented at 81 years old with a 3 cm lesion on the left labia. In the operating room, the vulvar lesion was injected circumferentially with indocyanine green. A 1 cm incision was made in the skin over the apex of the left femoral triangle carried past the underlying campers fascia. The tissue plain was developed overlying the femoral triangle using a tissue expander balloon. Under visual guidance, an 8 mm camera port and two 8 mm instrument ports were placed and the robot docked. The ipsilateral sentinel lymph nodes were identified using near-infared fluorescence and resected. We then performed a complete left superficial inguinal lymph node dissection. The right side was then performed in identical fashion. No sentinel node was identified on the right side. Radical hemivulvectomy was then performed without difficulty. All 11 lymph nodes were negative for disease. She was returned to the OR once for replacement of her JP drains. Her postoperative course was otherwise unremarkable and she is currently 15 months postoperative without complications or recurrence. Conclusions: Sentinel lymph node mapping and superficial inguinal lymph node dissection using robotic-assisted techniques and near-infared fluorescence is feasible and warrants further investigation.
Safety and efficacy outcomes for patients ages 65 and older treated with dose-dense chemotherapy for epithelial ovarian cancer.
Authors: Teplinsky Eleonora , Caldwell Haven Lindsay , Kohn Nina , Cheng Kit , Hoffman Mark Allan , Dos Santos Lisa A. , Sakaris Antoinette , Shih Karin , Lovecchio John L. , Whyte Jill Suzanne , Menzin Andrew , John Veena S. 
Published: September 2018

e17058 Background: Dose-dense chemotherapy is increasingly more utilized in the adjuvant treatment of patients (pts) with epithelial ovarian, fallopian tube, or primary peritoneal carcinoma (EOC), as compared to the conventional q3 week chemotherapy regimen. The safety and tolerability of the dose-dense regimen in pts ≥65 yrs old has not been well studied. We performed a retrospective analysis of pts with stage II-IV EOC treated at our institution with either regimen. Methods: We identified pts with stage II-IV EOC treated at Northwell Health from 2010-2015 who received adjuvant chemotherapy with the dose-dense (carboplatin q3 weeks/weekly paclitaxel) or the conventional (carboplatin and paclitaxel q3 weeks) regimen. Pts who received IP chemotherapy were excluded. Demographics, adverse events (AEs), dose delays/reductions and efficacy outcomes were evaluated. Results: 38 pts received conventional chemotherapy (median age 68 yrs) and 29 pts received dose-dense chemotherapy (median age 61 yrs). There were no differences in the frequency of grade ≥3 hematologic toxicities b/w the two arms. There were no differences in delayed or missed doses between the two arms but a higher proportion of dose reductions in the dose-dense arm ( P= 0.0472). Among pts treated in the dose-dense arm, 87.5% of women < 65 yrs old had at least one grade ≥3 AE when compared to 38.5% of women ≥ 65 yrs old ( P= 0.0161). There were no differences in dose delays, dose reductions, or missed doses when compared by age in the dose-dense arm. In the dose-dense arm, stage III-IV pts < 65 yrs old had a median time to progression (TTP) of 13.0 mo (95% CI, 6.7-13.8) and a median overall survival (OS) of 48.3 months (95% CI, 11.5-48.3). Pts ≥ 65 yrs old had a median TTP of 10.9 mo (95% CI, 8.7-12.7) and median OS of 35.9 mo (95% CI, 30.8-not reached). There was no difference in TTP ( P= 0.2154) or OS ( P= 0.9260) between the two cohorts. Conclusions: Our institutional experience of administering dose-dense adjuvant chemotherapy to women with EOC suggests that this regimen is likely safe in women ≥ 65 yrs old, with similar efficacy outcomes and should be considered for this population. Further study with larger sample sizes and in prospective trials is warranted.