bluuebunny/crossref_metadata_2025 huggingface dataset:
Repeat biopsy outcomes and change in QOL status at 1 year after active surveillance: Results from a Japanese multicenter prospective study and the PRIAS-JAPAN.
Authors: Sugimoto Mikio , Hirama Hiromi , Kakehi Yoshiyuki , Yamaguchi Akito , Koga Hirofumi , Hashine Katsuyoshi , Egawa Shin , Miki Jun , Shinohara Nobuo , Maruyama Satoru ,   PRIAS-JAPAN Study Group
Published: March 2020

e15127

Background: In Japan, two prospective multicenter active surveillance (AS) studies are under investigation. The 1st is a prospective Japanese AS study that has been carried out in favorable risk prostate cancer since 2002. The 2nd is the PRIAS-JAPAN; 30 institutions in Japan have been participating into the Prostate cancer Research International: Active Surveillance (PRIAS) study as the PRIAS-JAPAN since 2010. The objective of this study is to evaluate the outcomes of 1-year after AS including prostate re-biopsy and the change in QOL status using the two Japanese prospective cohorts. Methods: 134 patients with biopsy proven favorable risk prostate cancer were enrolled into study between January 2002 and December 2003. Triggers to start curable treatment were PSADT of 2 years or shorter or pathological progression at 1-year re-biopsy. AS remaining rate in 33.2% (median observation period: 78 months). On the other hand, PRIAS-JAPAN study was started since January 2010. Until December 2011, 189 patients were enrolled. 1-year after re-biopsy was recommended to all participants and QOL was assessed at enrollment and at 1-year after AS in both studies with Japanese version SF-36 and SF-8 respectively. Results: In the Japanese AS study, 64 patients who underwent re-biopsy, 42 met the pathological selection criteria again. Reclassification rate was 34.4%. In PRIAS-JAPAN, reclassification rate was 28% (p=0.467). There was no predictive parameter for reclassification in the Japanese AS study. On the other hand, number of positive cores was a significant predictive parameter for reclassification in PRIAS-Japan. Almost all domains of QOL at enrollment revealed better QOL than Norm-based Scoring (NBS). At 1-year after AS, there was no significant change and favorable QOL was maintained in both study. Conclusions: Instead of the time difference between the 2 studies was approximately 10 years, reclassification rate for the current AS cohort (PRIAS-J) was comparable or even lower than the former cohort. Health-related QOL of the Japanese patients who opted AS as an initial treatment was better than NBS and it has been maintained 1-year after AS.
Vinorelbine plus prednisone versus docetaxel plus prednisone as first-line treatment in metastatic hormone-refractory prostate cancer.
Authors: Abdel Halim Inas Ibraheim , El Sadda Wael M , Farouk Fatma , El Sherbeiny Esam , El Ashry Mohamed S
Published: March 2020

e15129

Background: Metastatic hormone refractory prostate cancer (mHRPC) is not curable and all attempts at therapeutic intervention have been based on palliating the disease. Androgen dependent prostate carcinoma responds poorly to chemotherapy. Recent protocols using vinorelbine, mitoxantrone and docetaxel have significantly improved response rate, survival and pain control for those patients. The study aims to compare the therapeutic benefit of the use of vinorelbine versus docetaxel both plus prednisone in patients with mHRPC. Methods: Sixty pts (50% gpA, 50% gpB) were enrolled between Mar 2005 and Sep 2007. All patients had histologically confirmed prostatic adencarcinoma with evidence of metastatic disease and progression on hormonal therapy. WHO PS O-2, adequate marrow, liver and renal functions. Patients were randomized to gpA; Vinorellrine (V) IV 30mg/m2 d1 and 8, or gpB; Docetaxe (D) IV 75mg/m2 d1. All patients received 5mg of prednisone orally twice daily for 5 days starting on day 1 of the tudy. Cycles repeated every 3 weeks. Patients with PD went off the study while those with CR, PR or SD continued treatment for 8 cycles maximum. Results: All pts were evaluable for response, toxicity and survival. The median age (gpA, gpB): 59 and 58 years, median WHO PS 1 (range 0-2) in both groups , Median basal PSA were 110 (90-780) and 120 (80-850) in group A&B respectively. The overall response rates were 53.3% (gpA) and 56.7% (gpB) P=0.24, the rates of PSA decline were higher in gpA than gpB (80% vs 70%) (p=0.27). Reduction of pain was better in patients receiving (V) than those treated with (D) (60% vs 50%) (p= 0.23). The improvement in the quality of life was higher in gp A than in gpB (50% vs 40%) but the difference was statistically insignificant. No WHO G3 or 4 toxicities in gp A. G3 alopecia (60%), G3 neutropenia (20%) were noted in gpB. Conclusions: Our results suggest that vinorelbine and docetaxel demonstrate similar efficacy as first line treatment for mHRPC. Vinorelbine is however better tolerated besides being a less costly therapeutic option in Egypt. Comparative phase III trial is needed to confirm these results.
Risk of mineralocorticoid excess syndrome with CYP17 inhibitor abiraterone in prostate cancer patients.
Authors: Itwaru Sandy Ann , Gopal Arun , Bashir Omer , Shim Joomee , Zhu Xiaolei , Wu Shenhong
Published: March 2020

e15140

Background: CYP17 inhibitor abiraterone acetate has been used for the treatment of patients with metastatic castration-refractory prostate cancer (CRPC). Hypertension, hypokalemia and edema are the major side effects associated with its use, and may be secondary to the excess of mineralocorticoids due to CYP17 inhibition. We performed a systematic review and meta-analysis of published clinical trials to determine the effect of abiraterone on the development of these side effects. Methods: Databases including Pubmed (July, 1966 to July, 2011), Web of Science, and abstracts presented at the American Society of Clinical Oncology meetings from 2008 to 2011 were searched to identify relevant studies. Eligible studies were prospective clinical trials of patients with prostate cancer receiving abiraterone acetate at the starting dose of 1,000 mg daily with available data on hypertension, hypokalemia and edema. Incidence and relative risk (RR) were calculated using a random-effects or fixed-effects model. Results: A total of seven studies including 1,387 patients with CRPC were selected for analysis. The incidences of all-grade hypertension, hypokalemia, and edema were 13.3% (95% CI: 8.3 to 20.5%), 31.4 % (95% CI: 12.5-59.5%), and 23.4 % (95% CI: 15.6-33.5%) respectively. The incidences of high-grade (grade 3 and above) toxicity were low, with a rate of 3.6% (95% CI: 2.6-5.1%), 2.8 % (95% CI: 0.9 to 8.2%), and 2.1% (95%CI: 1.3-3.2%) for hypertension, hypokalemia, and edema respectively. The risk of hypertension and edema did not change with and without the addition of prednisone (p=0.48 and p=0.40, respectively); however, the risk of hypokalemia was significantly reduced with the addition of prednisone (p = 0.003). In comparison with prednisone alone, the addition of abiraterone did not increase the risk of hypertension (RR 1.22, 95% CI: 0.82 – 1.83, p=0.31), but significantly increased the risk of edema (RR 1.36, 95% CI: 1.10-1.69, p=0.004) and hypokalemia (RR 2.04, 95% CI: 1.42–2.92, p<0.001). Conclusions: There were differential effects of abiraterone on the development of hypertension, hypokalemia, and edema in patients with advanced prostate cancer. Further studies are recommended for optimal treatment.
C11-acetate PET for docetaxel prednisone (DP) response assessment in castrate-resistant prostate cancer (CRPC).
Authors: Sharma Nancy , Menda Yusuf , Boles-Ponto Laura , Vaena Daniel A.
Published: March 2020

e15143

Background: C11- acetate (acetate) positron-emission tomogram (PET) has shown promise in detection of metastasis in prostate cancer in recent studies. Our study tested the feasibility of acetate-PET to predict early response to DP in CRPC. Methods: Men with metastatic CRPC for whom DP was indicated were enrolled in a prospective study of acetate-PET imaging and bone scans. Patients (pts) were imaged with both modalities at study entry and after 3 cycles of DP. DP was continued beyond cycle 3 until PCWG2-defined progression or toxicity. Treating physicians were blinded to acetate-PET results. No pts were on statins. The study was IRB-approved. Results: 6 pts with documented bone metastases were imaged (5 both pre and post-therapy.) Pre-therapy acetate-PET identified osseous metastases in all 6 pts. Remarkably, in one pt with previous radiation therapy, pre-therapy acetate-PET was negative for disease in the radiated area whereas bone scan showed persistent activity. The median number of DP cycles was 7 (5-16). 4 pts had ≥ 50% PSA decline. The median time to progression (TTP) was 5 months (mo). Of the 4 pts with PSA response, 2 had response on acetate-PET with TTP 5 mo and 10 mo respectively. One pt had > 50% PSA response but progression after 3 cycles based on PET, and met PCWG2 criteria for progression at 3.5 mo. The 4th pt with PSA response had stable findings on post-therapy PET and had 13 mo TTP. The pt who had no PSA response had stable post-therapy PET and had 2 mo TTP. Bone scan was stable in 3 pts, showed progression in 1pt and showed response in 1 pt. Conclusions: Response or progression on acetate-PET can be seen after a few chemotherapy cycles for CRPC. This study supports the exploratory inclusion of acetate-PET in future therapeutic clinical trials, with the potential to enhance the early prediction of treatment outcome. Acetate-PET might also allow more precise identification of viable target lesions than bone scan.
The clonality of immunoglobulin repertoire in prostate cancer-infiltrating B cells.
Authors: Trepel Martin , Stahl Phillip R. , Bokemeyer Carsten , Flammiger Anna
Published: March 2020

e15168

Background: There is emerging evidence that inflammation plays a role in prostate carcinogenesis. To better understand the cellular biology of the immune response in prostate cancer, we investigated the immunoglobulin (Ig) repertoire of tumor-infiltrating B cells. Methods: The Ig heavy chain variable region (VH) usage reflects the antigenic experience of tumor-infiltrating B cells and may help to identify potential therapeutic targets. We analyzed IgM-VH and IgG-VH transcripts of tumor-infiltrating B cells in four tumor samples of localized prostate cancer. Immunohistochemical staining revealed groups of CD20+ B cells surrounding neoplastic prostate glands. To exclude PCR amplification bias, two cDNA librarys were prepared from separate tissue sections of each tumor. IgM-VH and IgG-VH transcripts were amplified by RT-PCR from each cDNA library, cloned and sequenced. Results: Sequencing of a total of 80 IgM-VH and 80 IgG-VH PCR products (10 IgM-VH and 10 IgG-VH PCR products from each cDNA library) revealed an oligoclonal Ig repertoire in 3 of 4 and evidence of antigen experience of B cells in 4 of 4 prostate cancer samples. IgM and IgG B cell clones, defined by the same complementarity-determining region 3 (CDR3) and detection in two separate cDNA librarys, were widely distributed in the prostate. Prostate cancer-infiltrating B cells showed somatic hypermutation, Ig class switch and insertions or deletions indicating antigen experience. Conclusions: Clonally related B cells are widely distributed in the neoplastic prostate gland suggesting the recognition of a limited number of epitopes. Future studies will identify the antigens eliciting this immune response.
βIII-tubulin expression as a predictor of docetaxel resistance in metastatic castrate-resistant prostate cancer.
Authors: Sanchez Bertha E. , Gupta Nilesh , Mahan Meredith , Barrack Evelyn R , Reddy Prem-veer , Hwang Clara
Published: March 2020

e15174

Background: Docetaxel is a tubulin-targeting cytotoxic that remains first-line therapy in metastatic castrate-resistant prostate cancer (mCRPC) patients (pts) even though half of pts are reported to be non-responders. A predictive marker to identify those who will benefit from docetaxel-therapy will assist clinical decision making. High βIII-tubulin (TUBB3) expression has previously been reported to correlate with lack of response to taxanes in other cancers. We evaluated TUBB3 expression as a predictor of docetaxel-resistance in mCRPC. Methods: mCRPC pts treated with at least 3 cycles of docetaxel between 1990 and 2011 were identified retrospectively. TUBB3 immunostaining was performed on archival formalin-fixed, paraffin-embedded tissue. Stain intensity was scored from 0 to 3; 2 and 3 were interpreted as positive. Rates of PSA response were compared between pts with positive (+) and negative (-) TUBB3 expression. Two definitions of PSA response were evaluated (any PSA decline and at least 50% decline). Overall survival (OS) distribution between TUBB3+ and TUBB3- pts was estimated by the Kaplan-Meier method. Results: Of 73 pts, 26 (35%) expressed TUBB3. At diagnosis, the mean age was 65.7 years and the median Gleason score was 8. At the time of docetaxel therapy, the mean age was 71.2 years, the median PSA level was 70.9 (range, 0.2-5253) and 76% had ECOG performance status ≤1. The median number of docetaxel cycles was 7 (range, 3-18). The total dose of docetaxel was not different between groups (p=0.705). The median OS was 19.2 mo. TUBB3 expression was not correlated with any clinical or pathological characteristic (age, Gleason score, stage, ECOG, PSA, LDH, alkaline phosphatase, hemoglobin, visceral disease or chemotherapy before docetaxel). 65% of TUBB3+ pts had any PSA decline compared to 89% of pts with TUBB3- (p=0.0267). 52% of TUBB3+ pts had a PSA decline of ≥ 50% compared to 70% of TUBB3- pts (p=0.0144). Median OS for TUBB3+ pts was 16.8 mo compared to 20.4 mo in TUBB3- pts (p=0.039). Conclusions: High TUBB3 expression was associated with shorter OS and lower PSA response rates in mCRPC pts treated with docetaxel. These findings need to be validated prospectively.
A matched case control study in veteran patients with high cardiovascular risk (CVR) examining cardiac medication (CMed) prescribing differences between prostate cancer (PC) patients on androgen deprivation therapy (ADT) and men without PC.
Authors: Patel Yash R. , Reed Angela D. , Moore Marietta L. , Canfield Angela C. , Kruer James A , Hahn Noah M.
Published: March 2020

e15179

Background: Conflicting reports exist on associations between ADT and CVR in PC patients (pts). The current study tests the hypothesis that underutilization of CMeds in PC pts with known CVR contributes to their increased cardiac event rates. Methods: Veteran men without malignancy (no-PC, controls) and men with PC on ADT (cases) were consented through the IUSCC IRB-approved biorepository protocol. All pts had high CVR defined as the presence of > 2 of the following: age > 45, Body mass index (BMI) > 30 kg/m2, hypertension (HTN), hyperlipidemia (HL), diabetes (DM), and smoking history (SmHx). Prior coronary artery disease (CAD) qualified pts as severe CVR. Each case was matched with 2 controls in the following order of priority: prior CAD, HTN, DM, HL, SmHx, age, BMI, and race. CMeds prescriptions included in the table below were verified via VAMC pharmacy records. CMeds prescription differences between cases and controls were tested by one-sided chi-Squared testing for each medication and by logistic regression for different classes of medications. Results: Between 1/2007 and 6/2011, 53 cases and 254 controls were enrolled in the IUSCC VAMC clinics. After 2:1 matching, the final cohort included 53 cases and 106 controls. Demographics included: prior CAD – 27%, HTN – 60%, DM – 31%, HL – 40%, SmHx – 63%, BMI – median 29.7 kg/m2, Age – median 66 yrs. Controls were younger than cases (71.4 yrs cases – 63.1 yrs controls, p<0.0001). No statistically significant differences in CMed prescribing frequency were observed between the two groups. Conclusions: Differences in CMed prescribing practices between PC pts and no-PC men with high CVR is not a factor contributing to increased cardiac events in PC pts on ADT in our Veteran population. The study size warrants confirmation in a larger dataset. [Table: see text]
Survival benefits of second-line chemotherapy in metastatic castrate-resistant prostate cancer (CRPC) in a southeastern oncology community practice.
Authors: Gilmore James W. , Haislip Sally , Szabo Stephen , Sullivan Sean D , Ramsey Scott David , Kreilick Charles , Foltz Boklage Susan H , Sarma Syam , Asche Carl V , Shermock Kenneth M. , Sun Kai , Valluri Satish , Seal Brian S.
Published: March 2020

e15183

Background: Clinical studies showed that chemotherapy (CT) yields survival benefits for Metastatic Castrate resistant prostate cancer (CRPC) patients. This study investigated the relationship between patients with 2nd CT and OS using a real-world data. Methods: TheGeorgia Cancer Specialist Database containing chemotherapy, medical and pharmacy information, and lab results for patients with various types of cancer (2005-2011) was used. Patients (PTs) over 18 years of age with initial stage IV CRPC were followed from the first administration of CT (index date, ID) to the earlier of death or loss to follow-up (FU). PTs with one type of CT protocol (PL) were defined as first line CT PTs (1st), those with two types were identified as second line PTs (2nd), and those with three or more types were (3rd) line PTs. Kaplan-Meier survival curve was compared across the three groups using log-rank test. The impact of line of therapy on OS was further examined using multivariate Cox model with adjustment of PTs’ baseline age, race, Charlson Comorbidity Index (CCI), bisphosphonate use, and ECOG performance scores. Sensitivity analyses (SA) was conducted using different definition to define CT lines. Results: The study included148 PTs, with 86 (58.1%) as 1st, 38 (25.7%) as 2nd, and 24 (16.2%) as 3rd, 29 (19.6%) median age 73 with a range from 18 to over 82, 52.7% as race White, 33.8% African American, and 13.5% other or unknown race, average weight was 179 LB (range 100-279), average baseline PSA was 694 ng/ml (range: 0.05-21,743), 14 (9.5%) patients ECOG score of 3 or 4, 131 (88.5%) with one or more CCI comorbid conditions. Median survival was 17 months for overall, and 12, 19, and 23 months for 1st, 2nd, and 3rd line PTs, respectively (P=0.0355). Multivariate COX model found a higher likelihood of survival for 2nd line PTs (HR=0.361, P=0.006), but not for 3rd line PTs (HR=1.25, P=0.648). SA showed same results. Conclusions: This study suggested that second line of CT was associated with prolonged OS in metastatic CRPC. 3rd line CT survival benefit was not observed. Limitations include potential channeling bias and small sample size.
Changes in prostate-specific antigen doubling time (PSADT) prior to and after treatment with hormonal therapy (HT) in men with biochemically recurrent prostate cancer (BRPC): A preliminary analysis.
Authors: Sinibaldi Victoria J. , Huang Peng , Antonarakis Emmanuel S. , Carducci Michael Anthony , Eisenberger Mario A.
Published: March 2020

e15188

Background: PSADT is an important prognostic parameter in all clinical states of PCA. Intra -subject changes in PSADT prior to and after HT remains undefined. Methods: Men with rising serum PSA levels after local therapy were longitudinally followed from the hormone-sensitive (HS) to the castration-resistant (CR) state. PSADT was calculated according to standard formulas ( Pound et al., JAMA 1999) and previously identified prognostic subgroups (Antonarakis et al., BJU Int 2012; Freedland et al., JCO 2007) were used to evaluate the potential clinical significance of PSADT according to the following subgroups: [1] < 3 months (mo); [2] 3-8.9 mo, [3] 9-14.9 mo, and [4] ≥ 15 mo). Results: 55 men with BRPC who eventually developed CR disease on HT were retrospectively analyzed. The median age of HS men was 60 y (range (r) 43-78); CR men 66 y (r 43-87). Of all men, 28 had prior surgery (S), 5 had radiation (R), 14 had S+R, 7 had neoadjuvant /adjuvant HT + local therapy, and 1 had no local therapy. PSADT in the CR state was shorter than PSADT in the HS state (signed –rank test; p=0 .012). HS men with PSADT < 4 m had shorter overall survival than those with PSADT ≥ 4 mo ( 13.9 vs. 20.1 mo; HR ; 8.46). Changes in PSADT from the HS to the CR state are summarized in the Table below. The majority of men converted from a more favorable to a less favorable PSADT subgroup as they progressed from HS to CR states. Conclusions: PSADT tends to shorten from the HS to the CR states. The prediction of clinical outcome based on PSADT needs to account for the clinical state the patient is in, as PSADT may change within the same patient from state to state. [Table: see text]
Hormonal impact of salvage chemotherapy with carboplatin plus weekly docetaxel in patients with castration- and docetaxel-resistant prostate cancer (DRPC).
Authors: Reuter Christoph W. , Morgan Michael A. , Fenner Martin , Ivanyi Philipp , Grünwald Viktor , Ganser Arnold
Published: March 2020

e15190

Background: Recent data suggest that carboplatin may be effective in combination with docetaxel in DRPC. Platinum(II)-complexes interfere with steroid biosynthesis lowering testosterone levels by inhibiting CYP11A1, HSD3B1,2 and CYP17A1. Methods: Docetaxel failure/resistance was defined according to the Prostate Cancer Working Group (PCWG2007) criteria. Since February 2005, 68 consecutive DRPC pts were treated with at least two cycles of carboplatin (C) AUC5 iv for 30 min on day 1 every 4 weeks (q4w), docetaxel (D) at a dose of 35 mg/m2 iv for one hour on days 1, 8, (15) plus prednisone 2x5mg/day orally after receiving informed consent until disease progression or occurrence of intolerable adverse effects. Efficacy measures were done following PCWG recommendations. Free testosterone levels were measured before (n=42) and during DC chemotherapy (n=36). Results: Response of prostate-specific antigen (PSAR; ≥50% PSA) was observed in 32/68 (47.1%) patients. At the time of the current analysis (9/30/11) the median follow-up time was 13.6 months, 42/68 patients had died and 48/68 had progressive disease. Median progression-free survival (PFS) for all patients was 7.5 months (CI 95% 5.4, 9.6) and median overall survival (OS) was 18.6 months (CI 95% 11.7, 25.5). This regimen was reasonably well tolerated, with leukopenia/neutropenia as the most common reversible grade 3/4 toxicity (45.6/39.7%). Median free testosterone levels were 0.935 pg/ml before and 0.185 pg/ml during DC treatment (nadir levels, p<0.001; detection limit <0.18 pg/ml). Median serum androgene levels (T+DHT) were 0.26 ng/ml before and below the detection limit of <0.05 ng/ml during DC treatment (median nadir levels). While free testosterone levels before DC treatment were associated with lower PSAR (HR 6.32 CI 1.60, 25,0; p=0.009), free testosterone nadir levels <0.18 pg/ml during DC treatment were associated with higher PFS (HR 0.126 CI 0.04, 0.46, p=0.002) and OS (HR 0.07 CI 0.01, 0.59; p=0.014). Conclusions: These data suggest that carboplatin plus weekly docetaxel may be an important second-line treatment option for DRPC patients by inhibiting the testosterone biosynthesis.
Next-generation point-of-care immunoassay system for rapid and accurate determination of cancer markers in the physician office.
Authors: Zappala Stephen M , Libertino John A , Wein Alan J. , Vaughan E. Darracott , Scardino Peter T.
Published: March 2020

e15196

Background: Claros Diagnostics (Woburn, MA) has developed a novel multiplex immunoassay system designed to transition diagnostic tests performed at the centralized laboratory to the point-of-care (POC). The credit card-sized microfluidics disposable analyzes a fingerstick drop of whole blood with laboratory-quality results in 10 minutes, with significant ease-of-use. Total PSA was selected as an initial test to validate that this platform technology can achieve equivalent sensitivity, absence of interferences, etc. as compared to the reference laboratory. Further, the need to clinically validate the use incentives of such a POC system in optimizing the patient-physician encounter, practice efficiency, and overall quality of care were explored. Methods: We completed two consecutive studies measuring PSA in whole blood with the Claros system against the laboratory results in a matching serum sample. The first study entailed 72 patients from two sites and compared fingerstick samples against the laboratory Siemens Centaur serum assay, while the second study compared PSA results from 34 patients’ whole blood against the laboratory Roche E-170 serum assay. All studies were conducted under IRB approved protocols. Results: The PSA values measured in the 72 patients ranged from <0.1 to 8.3 ng/mL. Linear regression yielded a slope of 1.05 and a R2 value of 0.94. Range of PSA values in the second study on 34 patients were <0.1 to 13.5 ng/mL, from which the linear regression analysis yielded a slope of 1.04 and a R2 value of 0.98. In addition, specific data obtained between 0.1 and 1 ng/mL yielded an excellent correlation with a slope of 0.93 and a R2 value of 0.94. Overall (n=106) 7 patients were measured <0.1ng/mL by both assays. Conclusions: Quantitative results obtained with the Claros POC system using a fingerstick of whole blood correlated extremely well with laboratory assays over the clinically relevant range of PSA, including at very low PSA concentrations (essential to detect cancer recurrence post-intervention). Overall ease of use, the ability to use fingerstick blood and short time-to-result converge in improving physician practice efficiency and patient-physician interactions.
Clinical implications of insulin-like growth factor I (IGF-I) and II (IGF-II) in stage IIIB cervical cancer.
Authors: Patel Pooja Nandwani , Vyas Rakesh , Mehta Maitrik
Published: March 2020

e15505

Background: The IGF (Insulin like Growth Factor) family has been implicated in the pathogenesis of cervical cancer. We aim to correlate pre and post treatment levels of IGF-I and IGF-II in stage IIIB cervical cancer and identify if serum IGF-I and IGF-II can be used as a marker to predict response to chemo-radiotherapy. Methods: We recruited 80 previously untreated patients of histopathologically proven squamous cell carcinoma of stage IIIB cancer of uterine cervix from January 2011 to May 2011. The age of patients ranged from 30 to 65 years and were of ECOG performance status of less than or equal to 2. Along with the routine investigations the pretreatment serum levels of IGF-I and IGF-II were done by ELISA kits in all the patients. The serum level of IGF-I was 246.3 ± 72.5 ng/ml and IGF-II was 1585 ± 352 ng/ml. All patients were given concurrent cisplatin (30 mg/m2) weekly along with radiation (50Gy/25#) with conventional portals followed by two sittings of intracavitory radiotherapy (7.5 Gy each) on mHDR. Blood samples for IGF-I and IGF-II levels were collected before the start of the therapy, 1 month after the completion of treatment and 6 months after the completion of the treatment. Results: The trend seen was that mean IGF-I levels were always in the lower range as compared to IGF-II levels in all individuals. The mean serum levels of IGF-I and IGF-II in patients who achieve complete response (45%) returned to normal whereas the mean serum levels of IGF-I and IGF-II in patients who achieved partial response (43%) was 149 ng/ml and 838 ng/ml respectively. The mean serum levels of IGF-I and IGF-II in patients who achieved no response (12%) was 331 ng/ml and 1840 ng/ml respectively. Conclusions: The serum levels of IGF-I and IGF-II may be a reliable prognostic and predictive marker in cervical cancer however further large randomized studies are required to validate the results. IGF-I and IGF-II can serve as potential markers in cervical cancer to risk stratify patients, assess treatment response and possibly act as therapeutic targets in the future.
Using hospital claims data to identify ovarian cancer recurrence: A validation study.
Authors: Livaudais Jennifer C. , Egorova Natalia , Hayes Monica Prasad , Howell Elizabeth A. , Wisnivesky Juan P. , Franco Rebeca , Bickell Nina
Published: March 2020

e15513

Background: The use of administrative hospital claims data in research studies offers a promising alternative to conducting expensive chart abstraction to assess utilization and health outcomes. However, the validity of using claims data to capture ovarian cancer recurrence is unknown. Methods: We used two strategies to identify recurrent ovarian cancer: 1) a previously validated algorithm of secondary malignancy diagnosis codes used to identify recurrent breast cancer, adapted to ovarian cancer and 2) a new algorithm we created based on the timing and utilization of secondary chemotherapy or secondary debulking surgery for ovarian cancer. To identify secondary debulking surgery, which does not have its own billing code, weobtained codes used by gynecologic oncology billers from across the nation to identify these procedures. We identified all ovarian cancer patients who had undergone primary debulking surgery followed by initiation of primary chemotherapy at a single academic medical institution in NYC, between 2003 and 2010. We then ran the two recurrence algorithms on this population and randomly selected a sample of 50 patients to assess the sensitivity and specificity of each algorithm versus gold-standard chart abstraction data. Results: When applied to our sample of ovarian cancer patients, the sensitivity of the previously validated algorithm was 91% (95% CI: 57% to 99%), the specificity was 28% (95% CI 16% to 45%), the PPV was 26% (95% CI: 14% to 43%) and the NPV was 92% (95% CI: 66% to 99%). In contrast, the sensitivity of our newly developed algorithm to detect ovarian cancer recurrence based on hospital claims data was 100% (95% CI: 68% to 100%), the specificity was 87% (95% CI: 72% to 95%), the PPV was 69% (95% CI: 41% to 88%) and the NPV was 100% (95% CI: 87% to 100%). Conclusions: An algorithm culled from billers and clinical experts identifying timing and utilization of procedures measured ovarian cancer recurrence with a greater degree of accuracy than a previously validated algorithm to detect cancer recurrence. When complex chart reviews are not feasible, our claims-based algorithm can be used by researchers to answer important questions about ovarian cancer treatment effectiveness.
Features of clinical course of vulva cancer in reproductive patients.
Authors: Nerodo Ekaterina , Nerodo Galina A.
Published: March 2020

e15519

Background: The significant increase of vulva cancer patients in young and middle age is observed during the last ten years. Methods: To compare the clinical course of vulva cancer in reproductive patients (under 50 years of age) with the one in elderly agewe performed the comparative analysis of clinical characteristics of 839 vulva cancer patients, aged 20-90, with stages I-IV carcinoma who underwent standard complex antitumour treatment. Results: The reproductive group included 64 patients (7.6%), 775 patients (92.4%) were over 50 years. These included prevailed groups of 61-70 years of age – 38% and 71-80 years of age – 34%. Early stages of the disease were observed in 48% of all cases, st. III-IV – in 52%. In the reproductive group st. I was observed in 18.75%, st. II – 51.56%, st. III – 23.43%, st. IV – 6.25%. 70.03% patients of reproductive age had early stages of the disease, that is significantly higher than in the group of elderly patients: 51-70 years of age – 55%, 71-80 years of age – 40%, more than 80 years of age – only 25%(p<0.05). Age characteristics of vulva cancer patients in reproductive group were the following: 20-30 years of age – 10.9%, 31-40 years of age – 32.8%, 41-50 years of age – 56.25%. Organ-preserving operations carried out according to strict individual indications were performed to 35 sexually active patients in early stages. Relapses of the disease were revealed in 11 patients out of 64 (17%) in the reproductive group, and in 180 out of 775 (23.2%) patients in the elderly group(p<0,05) Relapses occurred in 8% of reproductive patients with st. I of the disease, st. II – 9%, st. III – 46%. Med locoregional free-survival was in st.I-72,3 mon. ,in st. II-61,3 mon., in st III-17,3 mon. All patients with inoperable tumour relapse underwent chemotherapy with subsequent tumour removal. Conclusions: Vulva cancer in patients of reproductive age is revealed in early stages more often that in elderly patients. There is a possibility to perform organ-preserving operations in young patients, which doesn't lead to relapse increase.
Human papillomavirus pevalence and persistence after chemoradiotherapy for carcinoma of the uterine cervix.
Authors: Noriega-Iriondo Maria Fernanda , Martinez Garza Laura Elia , Gonzalez Guerrero Juan Francisco , Barboza Quintana Oralia , Ruiz Sanchez Daneli , Zamudio Osuna Michelle , Martinez Rodriguez Jorge Luis , Gonzalez Vela Jose Luis
Published: March 2020

e15525

Background: Human papillomavirus (HPV) is associated with carcinoma of the cervix (CC). There is evidence that clearance of the virus occurs after chemoradiotherapy which is the standard treatment for this disease. Methods: Eligible patients with bulky IB to IVA CC were treated with once weekly cisplatin (40 mg/m2) chemotherapy and standard pelvic teletherapy and brachyterapy. HPV detection and typing was performed with DNA microarrays from liquid based cytologies before and 4 to 6 weeks after treatment completion. Clinical response was assesed by physical exam and liquid based cytology. Results: 23 patients (pt) with CC , were tested for HPV. Their age ranged from 33 to 80 years (mean 65), clinical stage I 8.6%, StageII 39%, stageIII 25.9% and stageIV 26.5%.VPH was found in 20 patients (87%). 34% of the patients had more than one type of HPV. 13 types of VPH were found,the most prevalent type was 16 in 47.8%, followed by type 72 in 13%.7 patients were lost to follow up during therapy. 16 patients were tested after completion of therapy ,there was HPV persistence in 5 patients (38.5%),whereas 61.5% cleared the virus. Of the persisting HPV the most prevalent type was 16 in two pt. and 61 in two pt. three pt had more than one HPV type after completion of therapy (types 11,81,35,39,56,84,66were found in different combinations in the pts). Response rate was as follows, 84.6% complete response,and two pt. had partial response. Viral clearance did not correlate with complete response in this study. Conclusions: HPV types 16 and 72 were the most prevalent in this population from northern Mexico. Infection with multiple viral types was common. Viral clearance occured in 61.5% and this did not correlate with complete clinical response. Persistence of multiple HPV types after completion of therapy may have unknown clinical and prognostic implications.
Clinical findings and medical management of hereditary breast-ovarian cancer without molecular diagnosis in a referral cancer center.
Authors: Morales-Vasquez Flavia , López-Basave Horacio Noe , Caballero Hector M , Mendez Herrera Maria del Carmen , Tirado Gomez Laura Leticia , Gallardo Rincon Dolores , Ruvalcaba Limon Eva , Herrera MaryTere , Urzua Lorena , Namendys-Silva Silvio A , Vidal Silvia ,   GICOM
Published: March 2020

e15527

Background: Ovarian cancer is the leading cause of death from gynecologic malignancies. Women at high risk of hereditary breast and/or ovarian cancer (HBOC) require specific management strategies. The goal of this study was to determine the prevalence of HBOC among patients in a referral cancer center. To analyze the pathologic and clinical characteristics of HBOC and examine whether survival is influenced by family history of breast or ovarian cancer. Methods: This retrospective study included all epithelial ovarian cancers seen at the National Cancer Institute of México from 2000-2009. Epidemiological and clinical variables were collected from the patients' medical records. Results: In 1071 cases, we found 15 patients with HBOC. The first pathology was breast cancer, and the ovarian cancer was diagnosed in average 8.23 years later. Only in 2 patients the ovarian cancer was before than breast cancer. The median age was 53 (35-69) years old at diagnosis for breast cancer and 51(40-75) years old in ovarian cancer. The advanced clinical stage was 13% for breast cancer versus 60% for the ovarian cancer. The histology was ductal carcinoma for breast cancer and serous papillary carcinoma for ovarian cancer with high grade. The recurrent disease was frequent for ovarian cancer. The median overall survival was 8 years (1-20 years). Conclusions: Recognition of when ovarian cancer is a substantial risk (in BRCA1 and BRCA2 carriers) is essential. However, the appropriate intervention is difficult to judge, and careful balancing is needed.
ESR-alpha promoter methylation to predict survival in low-grade ovarian cancer.
Authors: Engelstaedter Verena , Shi Rong , Heublein Sabine , Kuhn Christina , Friese Klaus , Mayr Doris , Jeschke Udo
Published: March 2020

e15529

Background: Ovarian cancer is one of the most lethal gynecologic malignancies and the leading cause of death among women with gynecological cancers. Different molecular markers have been studied for their prognostic relevance, but to date only CA 12-5 is used in routine diagnostic. Aberrant methylation of the estrogen receptor promoter (ESRp) was first described in colorectal cancer. Previous studies that described methylation of the ESRp in ovarian cancer suggested a potential role in cancer development. The aim of this study was to examine the methylation of the ESRp in a cohort of ovarian cancer patients in regard to its prognostic relevance. Methods: The study cohort consisted of 77 ovarian cancer patients that were diagnosed between 2000 and 2009 at the Department of OBGYN of the LMU Munich. A total of 50 patients died, 25 are still alive, 2 were lost to follow-up. Genomic DNA was isolated from paraffin-embedded cancer tissue and followed by bisulfite treatment. For detection of the methylated ESRp we used a sensitive real-time PCR. Results: Survival was significantly shorter for patients with aberrant promoter methylation within the subgroup of borderline, G1 and G2 tumors (31 patients; survival for methylated cases was 3.48 vs 4.91 years for unmethylated cases (p=0.010)). Within the small subgroup of borderline and G1 tumors (10 patients) survival for methylated cases was 4.73 vs 6.08 years for unmethylated cases (p=0.014). No significant difference of survival was observed for high grade (G3) ovarian cancer patients (p=0.745). Conclusions: We demonstrated for the first time that the methylation status of the ESRp might be a promising prognostic marker in ovarian cancer. ESRp methylation does not seem to be of prognostic relevance in high-grade ovarian cancer. In our study cohort a three-step grading system was used, but recent publications favor a two-step grading system. Thus, the G2 cases should be reevaluated to see whether they are G1 or G3. The difference in tumor etiology of low and high grade ovarian cancer might be responsible for the different prognostic relevance of ESRp methylation. Since our subgroup of borderline and G1 tumors is very small, these are preliminary results that have to be confirmed in a larger patient cohort.
Correlation between marital status and adequate pap test screening among Canadian women: An analysis of sociodemographic factors from the Canadian community health survey, 2007–2008.
Authors: Moretto Patricia , Canil Christina M. , Weberpals Johanne Ingrid
Published: March 2020

e15537

Background: Medical literature shows that marital status serves as an important factor which influences the likelihood of women undergoing cervical cancer screening. In Canada, women have universal access to health care as well as cancer screening facilities. This study was conducted to determine the association between adequate Pap test screening (APT) and marital status, stratified by age, and the prevalence of APT among the Canadian women. Methods: Data for the analysis were obtained from the Canadian Community Health Survey (CCHS), a national cross-sectional study, conducted during 2007 and 2008. The analysis included 22,530 women who were 18 to 69 years of age. The regression model used accounted for potential effect modification and confounders to assess the association between marital status (being married), and adequate cervical cancer screening (APT). Results: The weighted prevalence of APT was 75%, and was higher among married women (79%). The group with APT had a higher weighted prevalence of presence of a regular doctor, were white, had higher educational level and were non-obese, in comparison to the group with inadequate pap test (IPT). After adjusting for covariates, stratifying by age and weighting for the general population, married women, in the age groups 18-29 (RR 1.32, 95% CI 1.27;1.37), 40-49 (RR 1.07, 95% CI 1.03;1.12) and 60-69 years (RR 1.10, 95% CI 1.02;1.2) had a statistically significant increase in the risk of APT compared to non-married women. Conclusions: Marital status is associated with an increase in adequate Pap test screening in almost all age groups of the Canadian female population. This finding reinforces that providers of cancer screening services should target their efforts to improve the results among non-married women.
Aldehyde dehydrogenase activity in serous ovarian carcinoma.
Authors: Bareiss Petra M. , Fehm Tanja N. , Fischer Anna , Grauer Matthias , Kokorsch Philipp , Buehring Hans-Joerg , Pham Deborah , Staebler Annette , Wallwiener Diethelm , Fend Falko , Kanz Lothar , Lengerke Claudia
Published: March 2020

e15577

Background: Only specific subpopulations of tumor cells, so called cancer stem cells (CSC) may initiate and maintain tumors. The phenotype and molecular properties of ovarian CSC remain elusive. Aldehyde dehydrogenase (ALDH) activity characterizes (cancer) stem cells in different tissues and has been associated with ovarian CSC (Silva et al, 2011; Kryczek et al, 2012). Contradictory results have been reported on ALDH1 expression and prognosis in ovarian carcinoma. In this study, we explore the role of ALDH in serous ovarian carcinoma (SOC). Methods: Aldefluor-staining was used to assess ALDH activity in different ovarian carcinoma cell-lines and patient samples. ALDH+ and ALDH- cells isolated by FACS and ALDH1 versus control siRNA treated cells were analyzed in sphere forming, proliferation, BrdU and cell cycle assays. In vivo tumorigenicity assays including serial re-transplantations were performed in NOD/SCID/IL2Rγnull mice. ALDH1 and Ki67 expression were assessed immunohistochemically on a tissue microarray of 152 SOC samples. Results: ALDH+ cells formed more tumor spheres than ALDH- cells from the OVCAR-3 cell line and primary SOC and larger spheres (> 5.000 µm²) developed solely from ALDH+ cells. However, in vivo both cell fractions gave rise to tumors. Tumors contained both ALDH+ and ALDH- cells irrespective of the starting population. Notably, ALDH+ cells generated tumors more rapidly and induced larger tumors, suggesting a higher proliferative capacity. Immunohistochemical analysis of a larger cohort of SOC patients confirmed association of ALDH1 expression with the proliferation marker Ki67 (p=0.007). Surprisingly, co-stainings revealed that ALDH1 positive cells were mostly Ki67 negative and cell cycle synchronisation experiments using different agents showed ALDH induction in G0-enriched OVCAR-3 cells. However, inhibition of ALDH by treatment with three distinct siRNAs against ALDH1 did not alter cell cycle distribution. Conclusions: Our data suggest that ALDH is a correlative marker indicating, but not actively sustaining a quiescent stem-cell like state in SOC. Upon exit from G0, ALDH+ cells lose ALDH expression and induce a proliferative response.
Expression of vascular endothelial growth factor receptor (VEGF-R) and CD31 receptor (CD31-R) in high-grade neuroendocrine carcinoma of the uterine cervix (cNEC) and its association with prognosis.
Authors: Kuzman James A , Naraev Boris G. , Button Anna M , Samuelson Megan I , Goodheart Michael J , DeYoung Barry , O'Dorisio Thomas M. , Halfdanarson Thorvardur Ragnar
Published: March 2020

e15580

Background: High-grade cNEC is uncommon cancer, and the optimal treatment is unclear. It is not known if cNEC expresses surface proteins related to angiogenesis. The aim of this study is to evaluate the expression of proteins involved in angiogenesis, as well as their possible association with clinical outcomes. Methods: Expression of VEGF-R and CD31-R was analyzed with standard immunohistochemical methods in tumor specimens from 16 patients with cNEC seen at our institution from 1977 to 2010. CD31-R expression was estimated by analyzing microvessel density using a CD31 specific antibody. Intensity and percentage of cells expressing VEGF-R was determined. Univariate survival analysis was performed using a Cox Proportional Hazard Model. Results: VEGF-R was expressed in 15 out of 16 specimens whereas CD31-R was expressed in all specimens. Increased VEGF-R expression correlated with shortened survival but the association was not statistically significant (p=0.0544, hazard ratio=1.514, CI=0.992-2.309). A one unit increase in VEGF-R expression correlated with increase in the risk of death by 51.4%. CD31-R expression showed no significant association with survival (p=0.9638,CI=0.865-1.165). Conclusions: VEGF-R and CD31-R are expressed by most cNECs. Increased VEGF-R, but not CD31-R, expression may be associated with worse survival. Further exploration of the role of angiogenesis in cervical NETs is warranted.
Intraarterial high-dose cisplatinum (IAHDP) as a part of the treatment of relapsed or locally advanced tumors of the head and neck (H&N): A feasibility study.
Authors: Gonzalez Manuel Sureda , Moreno Antonio , Rebollo Joseba , Brugarolas A. , Cañon Rosa , Azinovic Ignacio , Crespo Aurora
Published: March 2020

e16000

Background: IAHDP has been employed as a part of the treatment of relapsed or locally advanced H&N tumors with controversial results (RADPLAT protocol). We hypothesize that patients (pts) with relapsed or locally advanced tumors in several locations can be treated with IAHDP, in order to achieve a response, to be followed by a consolidation with radiotherapy, surgery or both. Methods: Pts with relapsed or locally advanced tumors of the H&N were treated with IAHDP (150 mg/m2/wk), after an initial supraselective angiography performed with the goal of mapping adequately the arterial supply. Prevention of toxicity with hyperhydration and simultaneous and delayed thiosulfate was done according to the previous schema of the RADPLAT protocol. Results: From June 2007 to September 2011, 11 patients – 8 M/ 3F; age 37-77 y, median 56 y- were treated (10 H&N epidermoid carcinomas, 1 orbitary mts of adenocarcinoma of unknown origin). A total of 50 cycles were administered (2-9 per pt, median 4). In 4 pts IAHDP was part of the primary treatment; 7 pts were treated in relapse. Three pts were retreated after relapse, one of them two times. Five pts received radiotherapy simultaneously with IAHDP. Toxicity was generally mild and reversible. Mucositis g4 was observed in 3 cycles, facial edema requiring extra dexametasone in 7, pain during infusion in 9, nausea and vomiting in 3, lasting ipsilateral hypoacusia in 1, persistent trismus in 1. No significant alterations of renal function were observed. One pt progressed after the first cycle; 7 pts presented partial response (duration 1-6 m, median 2 m; 2 of them were converted to a complete response with surgery); 2 pts presented complete response with IAHDP simultaneous to radiotherapy. Four pts remained with no evidence of disease at 3+, 15+, 16+ and 38+ m respectively. Conclusions: IAHDP constitutes a feasible and promising therapeutic option for selected pts and a consolidation with surgery and/or radiotherapy after IAHDP is possible. Further development of this approach is warranted.