bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone scan index at baseline as a tool for predicting hematologic toxicity in metastatic castration-resistant prostate cancer patients eligible for radium-223 treatment.
Authors: Kothari Shalin , Sharif-Tabrizi Ahmad , Attwood Kristopher , Lamonica Dominick M , Levine Ellis Glenn , George Saby
Published: September 2018

e16513

Background: The prognosis of castration-resistant prostate cancer with skeletal metastasis (CRPCSM) is poor. The ALSYMPCA trial led to the approval of radium-223 (Ra223) in such patients. Factors that could predict hematologic toxicities associated with Ra223 remain poorly defined. We analyzed the utility of bone scan index (BSI) at baseline (BSI-B) as a predictive marker for such toxicities. Methods: This is a retrospective study of CRPCSM patients without visceral metastasis who received Ra223 at Roswell Park Cancer Institute from 2013 to 2015. BSI was defined utilizing the estimation of a numerical index (max, 70.8% for diffuse skeletal involvement) that expresses the fractional involvement of each bone by tumor. BSI-B values were classified into < first quartile ( < Q1), between first and third quartile (Q1-Q3), and > third quartile ( > Q3). The associations between BSI-B and different hematologic parameters [hemoglobin (Hgb), platelets (Plt), absolute neutrophil count (ANC)] over the Ra223 treatment duration were evaluated using linear mixed models. Results: A total of 79 patients were included in this analysis. The median Gleason score was 8 (range: 4-10) and the median age at first Ra223 was 71 years. Seventy percent of patients received 5 or more doses of Ra223. There was a significant association between BSI-B and Hgb (p = 0.005) and Plt (p = 0.011) levels at baseline and at all time points. The > Q3 BSI-B was associated with a greater drop in Plt from an elevated baseline with subsequent treatments of Ra223 [drop from a mean of 293.5±21.3 x109/L (n = 19) to 132.2±48.8 x109/L (n = 9) after sixth Ra223]; while such a decline was not observed for lower BSI-B (p < 0.001). The ANC decreased with each Ra223 in patients with > Q3 BSI-B but not in the ones with lower BSI-B (p = 0.003). Conclusions: Our work demonstrates that hematologic parameters at baseline and during Ra223 treatment are associated with higher BSI-B values, raising the possibility of BSI-B as a valuable tool for predicting the risk of cytopenias before initiating Ra223 in CRPCSM patients. Prospective validation is needed to confirm the utility of our findings.
Characterisation and treatment of patients with castration-resistant metastatic prostate cancer (mCRPC) developing neuroendocrine clonal divergence (NCD): A case series.
Authors: Bauernhofer Thomas , Belic Jelena , Pichler Martin , Bezan Angelika , Heitzer Ellen , Geigl Jochen Bernd , Stoger Herbert , Speicher Michael , Smolle Maria Anna
Published: September 2018

e16520

Background: The introduction of Abiraterone (Abi) and Enzalutamide (Enza) into treatment of mCRPC has led to a survival benefit. However, in a subset of patients treated with Enza/Abi, rapidly progressive disease with atpical metastatic spread develops. According to Eric Small et al. (ASCO 2015 Abstract 5003), 39% of metastases in mCRPC-patients treated with Enza/Abi have small cell neuroendocrine or mixed type histologies. Based on these findings we aimed at characterising NCD in a case series of 8 patients using 1) clinical, laboratory, radiological parameters, 2) molecular features generated by liquid biopsy and 3) to present outcome variables after treatment of these patients with combination chemotherapy carboplatin/etoposide (CE). Methods: Clinical, radiological, laboratory parameters, whole-genome sequencing of cfDNA (PlasmaSeq) and ctDNA taken at different time points during treatment were ascertained from 8 mCRPC-patients with NCD. Results: All patients presented with rapid tumour progression and atpical metastatic spread (3x liver, 3x lungs, 1x skin, 1x adrenal glands) during treatment with Enza/Abi. Laboratory findings revealed marked increase in CRP, AP and LDH levels and elevation of NSE ( > 5x times upper normal limit), whilst PSA levels were low or declining. All patients received Carboplatin AUC5 day 1 and Etoposid 100 mg/m3 day 1-3 q3w. In 7 out of 8 patients, initially high levels of CRP, LDH, AP and NSE decreased under CE therapy. Very good partial response on radiological examination was observed after 3-6 cycles of CE in these patients. One patient had progressive disease. Copy number profiles of ctDNA taken peri-interventionally revealed loss of androgen receptor and a clonal shift in comparison to profiles taken during endocrine treatment phase. Conclusions: Rapid clinical and radiologic progression, atypical metastases and sharp rise in LDH, CRP, AP and NSE levels combined with low PSA are indicative of NCD. For these patients, CE-based chemotherapy is a promising treatment option. In order to identify clonal shift from adenocarcinoma to neuroendocrine cancer, genetic profiling using ctDNA may be of use.
Prognostic value of neutrophil-to-lymphocyte ratio (NLR) in metastatic castration-resistant prostate cancer (mCRPC) pts receiving a new agent (NA)- based third line treatment: Final results from a multicenter Italian study.
Authors: Caffo Orazio , Bria Emilio , De Giorgi Ugo , Tucci Marcello , Biasco Elisa , Fratino Lucia , Facchini Gaetano , Iacovelli Roberto , Lo Re Giovanni , Scagnoli Simone , Morelli Franco , D'Angelo Alessandro , Verderame Francesco , Campadelli Enrico , Ricotta Riccardo , Napolitano Martina , Sartori Donata , Borsellino Nicolo , Sperduti Isabella , Maruzzo Marco
Published: September 2018

e16521

Background: High NLR has been reported to be a poor prognostic indicator in both first and second mCRPC lines, while no information is available concerning this issue in pts treated in third line therapy. The present study is aimed to assess the possible relationship between third line clinical outcomes and NLR in a series of mCRPC pts treated with a NA [abiraterone acetate (AA), cabazitaxel (CABA), or enzalutamide (ENZ)] after the failure of docetaxel (DOC) and another NA. Methods: We collected data of pts who received sequentially two NAs after DOC in 38 Italian hospitals. For each pt we recorded the clinical outcome of all treatments received after DOC. Cox regression analysis was used to assess the independent prognostic value of a series of pretreatment covariates, in terms of overall survival (OS), comprising NLR. Results: A consecutive series of 476 mCRPC pts with bone (86%), nodal (56%) or visceral (15%) mets, was collected. All pts received a NA-based third line: 135 received AA, 221 CABA and 120 ENZ. Data on NLR were available for 398 pts (84%). In the univariate analyses, the NLR as a discrete variable dichotomized according to the Maximally Selected Log-Rank statistics (optimal cut-off: 3.66), was significantly associated with both OS and progression free survival (PFS), calculated from the third line start (p < 0.0001). At the multivariate analysis, NLR, performance status, pain, hemoglobin, alkaline phosphatase, treatment with AA and with CABA were independent prognostic factors for PFS, while NLR, performance status, hemoglobin, PSA, and lactate dehydrogenase were independent prognostic factors for OS. In Kaplan-Meier analysis, the median OS from the start of third-line was higher (14.2 vs 9.3 mos) in pts with NLR ≤ 3.1 compared to those with NLR > 3.1 (log-rank; P < 0.0001). Similarly, the median PFS was 5.5 and 3.8 (log-rank; P < 0.0001) in pts with NLR ≤ 3.66 and > 3.66, respectively. Conclusions: Our results, observed in the largest cohort of mCRCP pts treated with NA-based third line after DOC and another NA, confirms that NLR is an independent factor for PFS and OS also in this population.
Expression of NY-ESO-1 cancer testis antigen in prostate cancer.
Authors: Jain Rohit K. , Xu Bo , Mehta Rutika Jitesh , Pop Elena , Mohler James , Odunsi Kunle , Chatta Gurkamal S.
Published: September 2018

e16544

Background: Poor outcomes in castrate resistant prostate cancer (CRPC) patients is a growing concern urging the need for innovative treatments. Cancer testis antigens (CTAs) like NY-ESO-1 are aberrantly expressed in several cancers including prostate cancer (PC). Given its tumor-restricted expression and ability to elicit spontaneous cytotoxic & antibody-mediated immune responses, NY-ESO-1 shows promise as an immunotherapy target. With the expertise of RPCI in NY-ESO-1 targeted therapeutics and limited information on NY-ESO-1 expression in CRPC, we sought this study. Methods: Immunohistochemical expression of NY-ESO-1 was analyzed in a series of PC samples from 2 different institutions. Two TMAs consisted of triplicate cores from 37 patients with localized PC (with cores from cancerous areas & the normal tissue adjacent to it), and 36 mCRPC patients. We also included 17 mCRPC whole sections for analyses. Intensity and percentage of NY-ESO-1 staining were recorded. The intensity was characterized as low (0-1+) and high (2-3+). Results: The median age in this cohort was 62 years. NY-ESO-1 IHC was positive for cytoplasmic staining in 33 of 111 (26.4%) evaluable cases including 41% in localized PC, 22.6% in benign areas adjacent to tumor, and 35.5% in CRPC. 23 (18.4%) had 1+, 7 (5.6%) had 2+ and 3 (2.4%) had 3+ cytoplasmic staining intensity. No statistical difference was noted in cytoplasmic staining with tumor grade. Gleason grade 8 -10 tumors (33 of 103 [35.4%]) correlated with lower intensity staining (0-1+) pattern (p = 0.028). NY-ESO-1 expression did not correlate with age, race, disease free or overall survival in this cohort. Conclusions: Heterogeneous NY-ESO-1 expression in PC and other tumors is linked to DNA methylation status of its promoter and tumor cells. We noted NY-ESO-1 expression in a third of the patients with CRPC, making it a credible immunotherapeutic target. NY-ESO-1 expression has been shown to be induced and upregulated in cancer by treatment with demethylating agent. Thus targeting NY-ESO-1 in concert with epigenetic modulation maybe therapeutically meaningful in patients with CRPC. Additional efforts at validating NY-ESO-1 expression in CRPC with CLIA approved IHC and qPCR assays (Omniseq) are ongoing and will be reported.
Variation in radiation oncology referral and adjuvant radiotherapy use following prostatectomy: A population-based study of health system performance.
Authors: Jin Chunzi Jenny , Hanna Timothy , Cook Earl Francis , Miao Qun , Brundage Michael Donald
Published: September 2018

e16551

Background: Evidence-based guidelines confirm a survival advantage of adjuvant radiotherapy (ART) for prostatectomy (RP) patients with high-risk pathology. The efficacy of deferred salvage RT is under evaluation as an alternative strategy, and guidelines recommend radiation oncology (RO) referral for discussion of options. We report RO referral patterns, ART use, and factors associated with these patterns in a contemporary population-based RP cohort. Methods: Electronic treatment records were linked to Ontario's cancer registry. Multivariable regression was used to evaluate clinical and health systems factors associated with RO referral and ART use ≤ 6 months post-RP. Results: From January to November 2012, 2,663 prostate cancer patients received RP in Ontario. Among 1,261 with adverse pathology, 492 (39%) were referred to RO ≤ 6 months post-RP, of which 51% received ART. Multivariable analysis demonstrated that RO referral was more frequent for cases of T3b/T4 disease [OR 17.87; p < 0.0001], T3a disease [OR 5.24; p < 0.0001], Gleason score 8-10 disease [OR 11.32; p < 0.0001], Gleason score 7 disease [OR 4.18; p < 0.0001], at least one non-apex margin positive [OR 4.20; p < 0.0001], an apex only positive margin [OR 2.60; p < 0.0001], RO referral prior to RP [OR 1.95; p < 0.0001], low RP volume hospitals [OR 2.50; p < 0.0001], and increased distance of patient residence from cancer center [OR 1.73; p = 0.01]. There was wide geographic variation in RO referral rates (range 6%-66%; p < 0.0001). Among patients seen by RO, only T3b/T4 disease [OR 5.37; p < 0.0001], T3a disease [OR 2.72; p < 0.0001], at least one non-apex positive margin [OR 2.81; p < 0.0001], and an apex only positive margin [OR 1.32; p < 0.0001] remained predictive of ART on multivariable analysis. Conclusions: Nonmedical factors are important determinants of whether patients are referred for discussion of ART post-RP. Post-RO consultation, treatment decisions are correlated with pathologic findings. Large inter-center variations persist in referral and treatment post-RP, suggesting that further understanding of the reasons for variation could improve access to potentially curative RT in this setting.
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.
Prognostic value of various subtypes of circulating DNA in ovarian cancer patients.
Authors: Minarik Tomas , Vlkova Barbora , Kalavska Katarina , Manasova Denisa , Kubickova Michaela , Jurik Andrej , Lengyel Tibor , Slezak Igor , Sadovsky Oliver , Niznansky Bohumil , Krkoska Milan , Kocova Lucia , Mardiak Jozef , Sufliarsky Jozef , Celec Peter , Mego Michal
Published: September 2018

e17092

Background: Patients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Circulating tumor DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Whether total circulating DNA, which can be assessed much easier without knowing the tumor-specific mutations, has similar informative value is currently unknown. The aim of this study was to evaluate the prognostic value of circulating DNA in advanced ovarian cancer. Methods: This prospective study included 67 patients (pts) with ovarian cancer treated with 1st line paclitaxel and carboplatin (25 pts) and bevacizumab (42 pts). Thirty-five patients had optimal debulking before chemotherapy. Circulating plasma DNA was quantified using real time PCR before administration of chemotherapy (67 pts) and after 6 cycles of chemotherapy (44 pts). Results: Total extracellular DNA (ecDNA), as well as extracellular DNA of nuclear (nDNA) and mitochondrial origin (mtDNA) significantly (p < 0.05) decreased after 6 cycles of chemotherapy (by 54%, 63% and 52%, respectively. Patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV (8604 vs. 16984 ge/mL, p = 0.03). Patients with lower baseline nDNA had superior progression-free (HR=0.35 (0.14-0.86)) and overall survival (HR=0.18 (0.04-0.77). The prognostic value of nDNA was confirmed independent of tumor stage and confirmed in multivariate analysis. Conclusions: Our data suggest that ecDNA of both, nuclear and mitochondrial origin, could be added to prognostic markers in ovarian cancer. This is of importance as this analysis does not require the knowledge of tumor-specific mutations in contrast to the quantification of tumor-derived ecDNA. Analysis of the dynamics and cell type-specific source of the ecDNA could shed light on its biology in cancer and might help to direct the treatment of ovarian cancer.
Survival disparity and racial differences in the use of neoadjuvant chemotherapy (NAC) compared with primary debulking surgery (PDS) in women with ovarian cancer.
Authors: Miller Eirwen M , Tymon-Rosario Joan , Xie Xianhong , Smith Harriet Olivia , Goldberg Gary L. , Kuo Dennis Yi-Shin , Nevadunsky Nicole Suzanne
Published: September 2018

e17099

Background: Studies demonstrate racial disparity in ovarian cancer survival though survival differences seem to be mitigated when patients receive similar care. We sought to identify whether racial disparity exists in the use of NAC or PDS for women with ovarian cancer. Methods: After IRB approval, all patients with epithelial ovarian cancer who received primary treatment at our institution from 2005-2016 were identified from our tumor registry. Charts were retrospectively reviewed for clinicopathologic and survival data. Categorical variables were compared with chi-squared and continuous variables with the student t-test. Kaplan-Meier was used to compare survival probabilities. Results: 302 evaluable patients were identified. 240 (79%) patients underwent PDS and 62 (21%) received NAC. Older patients, black patients, and those with stage III/IV disease were more likely to receive NAC. In a multivariate analysis controlling for stage and age, black race remained associated with NAC [OR 3.25 (95% CI 1.41-7.47), p < 0.01]. In a subgroup of advanced disease, stage III patients (n = 138) were more likely than stage IV patients (n = 52) to undergo PDS (78% v 44%, p < 0.01) and black patients were more likely than others to present with stage IV disease (39% v 22%, p = 0.01). NAC was utilized more frequently (48% v 24%, p < 0.01) in black patients compared with all other races. In the advanced stage subgroup analysis, patients that underwent PDS had a longer PFS than those that received NAC [HR 2.21 (95% CI 1.26-3.89), p = 0.01]. Conclusions: Racial disparity exists in the selection of PDS compared with NAC for patients with ovarian cancer and this disparity persists when controlling for stage and age. The choice of NAC or PDS may result in survival disparity. Further investigation is needed to examine other reasons, such as medical co-morbidities and disease distribution, for racial disparity in management. [Table: see text]
Acceptability of FitBit activity trackers for socioculturally diverse endometrial cancer survivors: A pilot study.
Authors: Miller Eirwen Murray , Rossi Amerigo , Samuel David , Ramirez Carolina , Viswanathan Shankar , Kuo Dennis Yi-Shin , Nevadunsky Nicole Suzanne
Published: September 2018

e17103

Background: Endometrial cancer survivors are the least physically active of all cancer groups. In past feasibility studies of a physical activity intervention for obese endometrial cancer survivors, we have found high adherence and significant improvements in quality of life and body composition but low recruitment (48%). The primary objective of this study was to assess the acceptability the FitBit Alta activity tracker among socioculturally diverse endometrial cancer survivors. Methods: After IRB approval, patients were approached for study participation at the time of routine follow-up in gynecologic oncology clinic. Eligible patients included those with a history of stage I-IV endometrial cancer diagnosed within the past 10 years who were not undergoing active therapy at the time of study participation. Participants were instructed to wear a FitBit Alta for 30 days. At the conclusion of the study period, patients received a phone call to complete an acceptability questionnaire. After 30 days of use, the FitBits were returned to provide detailed daily activity data for the duration of the study period. Results: Of 37 eligible identified patients, 30 agreed to participate in the study (81%). Recruitment to this study was significantly higher as compared with our historical exercise lifestyle intervention (48%, p < 0.01). Mean age was 65 and BMI 33 kg/m2 (19-64kg/m2). 70% reported stage I and II disease. Patients self-identified as 53% white, 23% black, and 33% Hispanic. 40% of patients had household incomes < $60,000 per year. Preliminary data shows that patients walk between 2,500 and 12,000 steps per day. Conclusions: Recruitment to the FitBit Alta was significantly higher than historically reported exercise lifestyle interventions at our institution. Additional research is needed to understand retention and patient satisfaction with lifestyle interventions using wearable technology.
Incidence and epigenetic factors associated with endometrial cancer in Appalachian Kentucky.
Authors: Manda Rohini , Raja Naga Praneeth , Shankar Uday , Dignan Mark , Kandagari Nagapavani
Published: September 2018

e17113

Background: Data from the US Cancer Statistics Working Group shows that the age-adjusted incidence of endometrial cancer was 25.6/100,000, 2009-2013 for the US and 24.9/100,000 for the Commonwealth of Kentucky. However, for the Kentucky River Area Development District (KR) in the Appalachian region, the rate was higher at 34.2/100,000. This investigation was designed to explore epigenetic factors related to the elevated incidence of endometrial cancer in the KR region of Kentucky. Methods: With IRB approval, retrospective data on women with endometrial cancer were abstracted from tumor registry records for the period 2005-2015. Data including age at diagnosis, family history of cancer, smoking, diabetes and demographic characteristics were analyzed using SPSS. Results: Data on 41 cases of endometrial cancer from 2005-2015 were included in the analyses. The age range was 37-87 with mean age 62. Of the 41 cases, 19.5% (8/41) were under age 50 at diagnosis. 2 out of 8 (25%) had family history of Lynch syndrome associated malignancies. 9 (22.0%) had family history of cancer. No significant associations between smoking, age at diagnosis and diabetes were noted. Conclusions: There is an increased incidence of endometrial carcinoma in Appalachian Kentucky in general, and elevated rates in women under age 50 compared to statewide and US rates. We have shown from our previous research that there is a higher incidence of lynch syndrome among young patients with colon cancer in Appalachian Kentucky. Similar findings were observed with endometrial cancer from this analysis. Further evaluation and genetic testing for any association with Lynch syndrome in this age group is needed.
Prognostic significance of performance status in patients with head and neck squamous cell carcinomas (HNSCC) receiving immune checkpoint monoclonal antibodies (ICmAB) in a single institution.
Authors: Hwang Victoria , Martins Renato G. , Eaton Keith D. , Chow Laura Quan Man , Baik Christina S. , Goulart Bernardo H. L. , Lee Sylvia Mina , Santana-Davila Rafael , Rodriguez Cristina P.
Published: September 2018

e17506

Background: The anti-PD1/-PDL1 ICmABs can result in objective responses in some (13-20%) patients (pts) with HNSCC. We evaluated clinical factors that may predict oncologic outcomes. Methods: We identified pts who received an ICmAB at our institution and retrospectively collected demographic, tumor, treatment, progression, and survival data. The Kaplan Meier method was used to estimate survival. Log-rank and Wilcoxon tests were used to explore associations between clinical features and outcomes. Results: 55 pts received ICmAB in a clinical trial at our center from 8/2012 to 12/2016. The median age was 64 years, 13 (24%) were female, and 45 (82%) were white. ECOG Performance Status (PS) was 0 and 1 in 23 (42%) and 32 (58%) pts, respectively. 29 (53%) were current/former smokers who smoked a median of 20 (range 0-70) pack years. Primary sites included: oropharynx (OP) 31 (56%), oral cavity 9 (16%), nasopharynx 6 (11%), nasal cavity 3 (5%), hypopharynx (HP) 2 (4%), unknown (UK) 2 (4%), and skin 2 (4%). 28 (51%) were p16+, with the following primary sites: OP in 26, UK in 1, and HP in 1. 53 (96%) received prior curative intent therapy. A median of 2 (range 0-5) lines of systemic therapy (including curative intent) were given prior to ICmAB initiation, and 31 received an ICmAB as a single agent. There were 19 (35%) objective responses with 1 complete response, and 14 (25%) had stable disease. With a median follow-up of 12 months (m), the median overall survival (OS) was 15m (95% CI 11,47), and median time to progression was 4m (95% CI 2.2, 6.8). An ECOG PS of 0 vs 1 was associated with superior OS (36m vs 11m p = 0.001). Tobacco use, p16+ disease, single agent ICmAB vs. combination, number of lines of prior systemic therapy, or radiation therapy within 3m prior to ICmAB initiation did not appear to have a relationship with survival. Conclusions: A PS of 0 predicted for more favorable OS among HNSCC pts receiving ICmAB in this single center retrospective cohort. In contrast to data with chemotherapy, established prognostic markers (including p16+ and limited/no tobacco use) did not appear to impact survival.