bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of oligoprogressive, metastatic castration-resistant prostate cancer (mCRPC) amenable to stereotactic ablative radiotherapy (SABR) in men undergoing abiraterone acetate (AA) therapy.
Authors: McDonald Erica , Cheng Sierra , Arciero Vanessa Sarah , Saluja Ronak , Zukotynski Katherine A. , Cheung Patrick , Emmenegger Urban
Published: September 2018

e16509

Background: SABR is increasingly used for treating men with oligometastatic prostate cancer, a state between loco-regional and widespread metastatic disease that exists de novo, presents as oligorecurrence, is treatment-induced, or occurs as oligoprogression. The latter is a clinical situation where a limited number of metastatic tumor sites progress (usually defined as ≤3-5), while all other metastases are controlled by a given systemic therapy. The frequency of oligoprogression amenable to SABR is unknown. Methods: Thus, in a retrospective chart analysis we studied the progression pattern of 35 men with chemotherapy-naïve mCRPC undergoing AA therapy, and of 20 men undergoing AA therapy after docetaxel chemotherapy. Applying RECIST1.1 and/or PCWG2 criteria, patients (pts) were considered SABR candidates if they radiologically progressed in ≤5 distinct metastatic locations, while all other sites were stable or responding. Results: In chemotherapy-naïve men, pre-AA metastatic lesions were located in bone (94%), lymph nodes (49%), lungs (17%) and liver (3%), whereas progression during AA therapy occurred in bone (89%), lymph nodes (49%), lungs (14%) and liver (9%). 12 pts (34%) met the criteria of oligoprogression with a median of 2 progressive lesions/pt (range 1-5). 8 pts presented with bone progression only, 3 with nodal progression, and 1 pt with combined bone/nodal progression. Post-docetaxel pts had pre-AA metastatic lesions located in bone (75%), lymph nodes (35%), lungs (5%) and liver (5%). Progression during AA therapy occurred in bone (80%), lymph nodes (75%), lungs (20%) and liver (5%). Only 1 pt met oligoprogression criteria with a single progressive bone metastasis. Conclusions: A sizeable number of men with chemotherapy-naïve mCRPC progressing during AA therapy might be considered for SABR. By contrast, progression of post-docetaxel mCRPC treated with AA is typically widespread. Further efforts are needed to identify criteria for oligoprogressive pts most suitable for SABR with sustained benefit versus men that may progress rapidly with widespread metastases following radiotherapy.
A pilot study of the effects of androgen deprivation therapy on physical function and comprehensive geriatric health in older men with prostate cancer.
Authors: Kessler Elizabeth Riley , Flaig Thomas W. , Lam Elaine Tat , Breaker Kathryn M. , Wacker Michael , Jankowski Catherine
Published: September 2018

e16510

Background: Alteration of the androgen axis through androgen deprivation therapy (ADT) is the mainstay of prostate cancer (PCa) treatment. Unfortunately, the resultant hypogonadal state has detrimental effects on muscle and bone and may impair physical function (PF). Older patients may be more vulnerable to PF changes while on ADT. We conducted a pilot study to evaluate the changes in PF and geriatric health in older men initiating ADT using tests easily employed in routine clinical practice. Methods: Men with PCa initiating ADT were enrolled and were assessed every 3 months (mos) for up to 12 mos. PF was measured using the short physical performance battery (SPPB) and geriatric health was screened using the Vulnerable Elders Survey (VES13) which predicts potential death or decline over 2 years. The primary endpoint was change in SPPB and VES13 at 3 mos. Results: We enrolled 17 patients with a median age of 75 years (range 67-85) beginning ADT therapy. Fourteen patients had metastasis, 2 had locally advanced disease, and 1 had biochemical recurrence. The majority had Gleason score (GS) 7 cancer (9/17), 7/17 GS 8-10, and 1/17 with GS 6. Eight patients had normal SPPB baseline scores and 9 had moderate impairment (moderate frailty risk) (Mean 10, SD 1.71). Seven had a clinically significant decline in the SPPB at 3 mos, with 1 patient testing as severely impaired. The VES13 screening tool identified 6/17 patients as vulnerable at baseline (Mean 3, SD 3.92). At 3 months, 3/17 patients had a decline in VES13 and 6/17 with an improvement. Of the 10 patients who were followed for at least 6 months, 5 had worsening of the VES13 and 2 had a worsening in SPPB. Conclusions: Older patients initiating ADT have baseline vulnerabilities in geriatric health with little immediate detriment after treatment initiation, perhaps due to overall health improvement with treatment initiation. Changes in PF, however, are seen within the first 3 months of ADT in nearly half of our patients, warranting further investigation into early rehabilitation of men even on short-term ADT. The SPPB is easily employed in clinic and important as reliance on VES13 alone is likely to miss patients with PF impairments.
Hospital admissions (HA) among chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) patients newly treated with enzalutamide (ENZA) or abiraterone (ABI).
Authors: Quek Ruben G.W. , Gilligan Adrienne M. , Kent Shia T. , Gregory Christopher , Schultz Neil M. , Flanders Scott , Brown Bruce A. , Wong Elaine Karol , Barlev Arie
Published: September 2018

e16524

Background: ENZA and ABI are approved to treat mCRPC in chemotherapy-naïve patients; few real-world analyses exist to compare HA pre- and post-treatment. This study characterized and compared incidence and incidence rate ratios (IRRs) of HA pre/post initiation of ENZA or ABI in chemotherapy-naïve mCRPC patients in the US. Methods: Patients aged ≥ 18 years who initiated ENZA or ABI (2 cohorts) from Jan 2014–Dec 2015 were identified retrospectively from MarketScan® Databases. The index date was the initiation of ENZA or ABI after ≥ 6 months of pre-index continuous health plan enrollment. We identified the top 10 HA incidences using ICD-9/10 CM inpatient claims (separate primary and any position) and assessed pre-/post-index IRRs within each cohort. Generalized estimating equations accounting for within-patient correlation and difference-in-differences regression were fitted to compare IRRs between cohorts. Results: A total of 1603 (ENZA, 656; ABI, 947) patients were included. Mean age was 73 years in both cohorts; mean (standard deviation) Deyo-Charlson Comorbidity Index was 7.9 (2.8) for ENZA and 7.8 (2.9) for ABI; the top 10 HA incidences included cardiac disorder, dyspnea, hypokalemia, liver toxicity, pneumonia, renal impairment, skeletal-related events (any, surgery and fracture) and urinary tract infection. IRRs of HA (any position) due to cardiac disorder, dyspnea, hypokalemia, liver toxicity and pneumonia were significantly higher for post- vs pre-ABI-treated patients (IRR [95% CI]: 1.63 [1.22–2.17], 1.90 [1.21–2.98], 3.13 [1.46–6.71], 2.24 [1.36–3.69] and 2.40 [1.41–4.10]). IRRs of HA (any position) due to cardiac disorder, dyspnea and hypokalemia were significantly lower in the ENZA cohort than ABI cohort (1.02 vs 1.63, 0.84 vs 1.90, 0.65 vs 3.13; all P < 0.05). No statistical significance was observed for any other HA comparisons (primary or any position) between or within ENZA and ABI cohorts. Conclusions: Among chemotherapy-naïve mCRPC patients, significant increases in multiple HA IRRs were observed post- vs pre-ABI treatment, and IRRs were significantly lower for ENZA- vs ABI-treated patients for multiple HA.
Racial differences in patterns of treatment among men first diagnosed with advanced prostate cancer.
Authors: Beebe-Dimmer Jennifer Lynn , Ruterbusch Julie J. , Schwartz Ann G. , Schwartz Kendra L. , Holowatyj Andreana , Heath Elisabeth I.
Published: September 2018

e16527

Background: A small proportion of men (~4%) are newly-diagnosed with advanced stage prostate cancer (PCa) and experience poorer survival compared to men diagnosed with local or regionally-advanced disease. Prostate cancer mortality is higher in African Americans (AA) than in non-Hispanic whites (NHW), with a marginally higher proportion of AA men first diagnosed with advanced disease. We sought to describe recent patterns of treatment among men diagnosed with de novo AJCC stage IV PCa. Methods: We used the Surveillance, Epidemiology and End Results database linked to Medicare Claims files to identify men diagnosed with advanced PCa between 2007 and 2011, with follow-up through 12/31/2013. We examined patterns of treatment (surgery, radiation, chemotherapy, and hormonal therapies) as well as rarer modalities and drugs included in Medicare Part D, both overall and by race. Results: Of the 6,906 men eligible for this study, 74.6% were NHW and 13.1% were AA with a median survival of 32 months among all patients. Survival was poorer among AA compared to NHW (p < 0.0001). Among the significant predictors of mortality were TNM stage, age at diagnosis, race, Gleason grade, and the presence of comorbid conditions. Androgen Deprivation Therapy (ADT) was the most widely-used treatment (78.7%), followed by radiation therapy (31.2%) and chemotherapy (30.2%). AA patients were significantly more likely to go without treatment (p < 0.0001) compared to NHW patients. This finding did not change after excluding men who died within 3 months of diagnosis or men without distant metastatic disease (T4 or N1 and M0/MX). The frequency of nearly all forms of treatment was lower among AA patients with two notable exceptions; orchiectomy was significantly higher (11.8% vs. 6.9%), and among Medicare Part D enrollees, use of the progesterone Megace (27.7% vs. 17.2%). Conclusions: ElderlyAA patients newly diagnosed with stage IV PCa have shorter overall and disease-specific survival compared with NHW. Results from this study suggest less aggressive treatment may contribute to poorer survival. Understanding drivers of treatment-related decisions are critical in reducing racial disparities in survival among men with advanced PCa.
Association of neuroendocrine phenotype with platinum chemotherapy outcomes in men with metastatic prostate cancer.
Authors: Humeniuk Michael Sandon , Gupta Rajan T , McNamara Megan Ann , Ramalingam Sundhar , Harrison Michael Roger , George Daniel J. , Wu Yuan , Healy Patrick , Armstrong Andrew J.
Published: September 2018

e16532

Background: DNA repair defects are common in men with mCRPC, and platinum chemotherapy may have a role in selected patients. We aimed to determine whether neuroendocrine variant prostate cancer (NEPC) is associated with a greater response to platinum chemotherapy, as compared to CRPC with adenocarcinoma histology (AdenoCRPC). Methods: We conducted a retrospective cohort analysis of all patients with prostate cancer treated with platinum chemotherapy at the Duke Cancer Center between 2005-15. The primary endpoint was objective response rate (RESIST v1.1; ORR); secondary endpoints were PSA decline, progression-free (PFS) and overall survival (OS). Outcomes were compared by histologic phenotype (NEPC vs. AdenoCRPC). Results: Between 2005-2015, 73 men, including 56 with AdenoCRPC and 17 with NEPC, were treated with platinum-based chemotherapy for mCRPC. Carboplatin-docetaxel and carboplatin/cisplatin etoposide were the most common regimens. Fifteen men (21%) were M1 at diagnosis. Among NEPC patients, 3 had primary NEPC/small cell carcinoma at diagnosis, while 14 had NEPC transformation after hormonal therapy. Overall, 24% of NEPC men received prior docetaxel vs. 75% of AdenoCRPC men. Partial responses were observed in 59% in men with NEPC vs. 25% for AdenoCRPC. Primary progressive disease occurred in 24% (NEPC) vs. 48% (AdenoCRPC). PSA declines with platinum chemotherapy were more common in NEPC (median 72% decline) vs. AdenoCRPC (median 24% decline). There was no significant difference in median PFS or OS between phenotypes (NEPC PFS 5.1 mo, OS 8.5 mo; AdenoCRPC PFS 4.3 mo, OS 10.0 mo; p = NS). For second platinum chemotherapy, ORR and PFS in NEPC vs AdenoCRPC were 67% and 5.2 months vs. 14% and 4.6 months. Conclusions: Our data suggest that men with NEPC histology have a greater probability of objective response and PSA decline with platinum chemotherapy vs. men with AdenoCRPC. However, PFS and OS are similar across histologic phenotypes, indicating similar times to resistance to platinum chemotherapy. Biomarkers of platinum sensitivity are needed, and evaluation of DNA repair defects in this setting may provide a greater opportunity for precision medicine approaches to DNA damaging agents.
Prostate clinical outlook visualization for patients and clinicians considering cyberknife treatment: A personalized approach.
Authors: Park Jihwan , Rho Mi Jung , Dritschilo Anatoly , Collins Sean P. , Suy Simeng , Choi In Young , Mun Seong K.
Published: September 2018

e16549

Background: When a patient presents with localized prostate cancer, referral for radiation oncology consultation includes a discussion of likely outcomes of therapy. Among current radiation treatments for prostate cancers, hypo-fractionated stereotactic body radiation therapy (SBRT) has gained clinical acceptance based on efficacy, short duration of treatment and potential radiobiological advantages. The prostate Clinical Outlook (PCO) visualization system was developed to provide the patient and the clinician with a tool to visualize probable treatment outcomes using institutional, patient specific data for comparing results of treatment. Methods: We calculated the prostate cancer outlooks for each prospective patient using the EPIC-26 quality of life parameters based on clinical outcomes data of 580 cyberknife SBRT treated prostate cancer patients. We applied Kaplan-Meier analysis using the ASTRO method for disease free likely outcome and the PCO nomogram to calculate parameters for quality of life. Open source R, R/Shiny, and MySQL were used to develop a modularized architecture system. Results: PCO presents patient specific risk scores in a gauge chart style and risk free probability bar plots to compare treatment data of cyberknife patients. PCO generates reports, in PDF and HTML, which consist of a comparison chart of risk free probabilities and gauge charts of risk scores. This system is now being expanded as a web-based service to patients. Conclusions: PCO visualized patient specific likely outcomes were compared to treatment data from a single department, helping the patient and the clinician to visualize likely outcomes. The PCO approach can be expanded to other specialties of oncology with the flexible, modularized architecture which can be customized by changing parameter variables for the modules.
Evaluation of microarrays for measuring cell cycle progression (CCP) gene expression.
Authors: Stone Steven , Cooperberg Matthew R. , Flake Darl D , Davis John W. , Moul Judd W. , Tward Jonathan David , Brawer Michael K.
Published: September 2018

e16566

Background: A CCP score has been developed and validated to provide prognostic information in prostate cancer. To date, our studies have exclusively used qRT-PCR to measure CCP gene expression, which is generally considered the ‘gold-standard’ for measuring RNA expression levels. However, qRT-PCR allows for the interrogation of a relatively small number of genes. Because prostate cancer biopsies provide very limited tissue, there is interest in evaluating RNA expression platforms that could simultaneously integrate CCP genes and other less characterized targets that might be clinically useful. Here we evaluate the ability of microarrays to measure CCP gene expression. Methods: CCP scores for 1636 radical prostatectomy samples submitted for commercial testing were generated from the mean expression of 31 CCP genes and 15 housekeeping genes as determined by qRT-PCR. CCP scores were also generated from several publically available Affymetrix microarray expression data sets (Nakagawa et al. 2008, Karnes et al. 2013, Klein et al. 2014, Boormans et al. 2013, Taylor et al. 2013) by averaging the intensities (RMA processed, base 2 log scale) of the 31 CCP genes. Expression data were evaluated by comparing CCP score range and pairwise correlations between CCP genes. Results: The average pair-wise correlation in the commercial cohort using qRT-PCR was 0.67. The pair-wise correlations in the microarray studies were significantly lower, ranging from 0.17 (Klein) to 0.58 (Boormans). Importantly, the data in Boormans et al. was generated from frozen tissue. The CCP score in our commercial cohort ranged from -2 to 3 (base 2 log scale) with a standard deviation (SD) of 0.79. In contrast, the CCP score range in microarray studies was highly truncated with SDs ranging from 0.12 (Nakagawa) to 0.46 (Boormans). Conclusions: Expression of CCP genes as determined by microarrays correlates weakly with expression measured by qRT-PCR, with reduction in normally observed pairwise correlations among CCP genes and the range of CCP scores. This is especially true if the RNA is derived from fixed tissue. As a result, microarray generated CCP scores cannot be assumed to be a valid surrogate for qRT-PCR generated scores for prediction of patient outcome.
Integrated, structured reporting and diagnosis of localized prostate cancer.
Authors: Hofstraat Hans , Hoffmann Ralf , Janssen Marco , de Klerk Maud , Loos Marc , Jaederling Frederik , Akre Olof
Published: September 2018

e16573

Background: To date 80-90% of men with primary prostate cancer are diagnosed with localized disease with a wide range of risks of future tumor progression. To optimize the balance between tumor removal and preserved continence and erectile function, it is essential to integrate all available information on tumor location, tumor characteristics, and baseline clinical data. Methods: We have developed a cloud-web-based technology allowing flexible access to the clinical data with close integration to the existing IT-environment like the hospital information management systems. The system allows the systematic and structured reporting of medical data generated by the involved disciplines of urology, laboratory, radiology, pathology, and (radiation) oncology, and patient reported health status and outcomes. Results: By use of the developed data integration platform we have collected diagnostic data of a prostate cancer case example scheduled for a multi-disciplinary primary treatment decision. The data comprises the patient health conditions, laboratory measures, multi-parametric MRI, localization information of MRI/US fusion guided biopsies, histo-pathology outcomes of prostate biopsy specimen, and patient reported outcomes on urinary and sexual function status. The collected data was presented in a visually integrated way and was used to discuss in a multi-disciplinary team, with the consistencies or discordances of findings across the various medical domains involved. Based on the discussion a primary treatment decision was concluded for this patient. Conclusions: The developed IT system to integrate heterogeneous medical data was successfully tested in a multi-disciplinary clinical setting. All required clinical variables to provide an informed primary treatment decision for a patient with primary localized prostate cancer was available in the system for discussion during the multi-disciplinary team (MDT) meeting and was presented in a clear visual way to support the interactive discussions between MDT members representing different clinical specialties.
Effects of exercise on dyspnea and cancer-related fatigue in patients with prostate cancer.
Authors: Cole Calvin , Peppone Luke Joseph , Kleckner Ian , Lin Po-Ju , Dunne Richard Francis , Fung Chunkit , Loh Kah Poh , Asare Matthew , Mustian Karen Michelle , Morrow Gary R.
Published: September 2018

e16580

Background: Dyspnea and fatigue are two of the most common symptoms reported by patients with advanced cancer. Patients with dyspnea report an inability to complete activities of daily living (ADL) and impaired quality of life (QOL). Exercise has been shown to reduce cancer-related fatigue (CRF); however the relationships between dyspnea, CRF, ADL and QOL are unclear. The purpose of this study is to examine the effect of exercise on dyspnea, CRF, ADL and QOL. Methods: A secondary data analysis was performed on a two-arm randomized controlled trial investigating the influence of exercise on prostate cancer patients treated with hormone (androgen deprivation therapy) and/or radiation therapy. Exercise for Cancer Patients (EXCAP©) is a 6 week home-based program that includes progressive aerobic and resistance band training. Participants were randomly assigned to usual care with EXCAP© or usual care only (UC). Dyspnea, CRF, ADL and QOL were measured using the Multidimensional Fatigue Symptom Inventory (MFSI) and a Clinical Symptom Inventory (SI) at pre- and post-intervention. Results: Participants included 57 sedentary prostate cancer patients, average age 67 ± 8 years. Mean changes in dyspnea showed a positive, association with mean changes in CRF (SI r = .525; p < .01, MFSI r = .327; p = .08) in the EXCAP group but not in the UC group. Dyspnea changes were also positively associated with changes in exercise behavior (r = .590; p < .01), ADL (r = .684; p < .01), and QOL (r = .532; p < .01) in the EXCAP group, no association was found in the UC group. Furthermore, exercisers who reported the greatest improvements in dyspnea also reported greater improvements in CRF = 2.2 (p < .05), ADL = 1.8 (p < .01), and QOL = 2.4 (p = .01). Conclusions: Exercise-induced improvements in dyspnea are associated with improvements in CRF, ADL and QOL in prostate cancer patients. Additional research is needed to further understand these results. NCORP UG1 CA189961, R25 CA102618, DOD PC061518 Clinical trial information: NCT00815672.
Effect of PectaSol-C modified citrus pectin (P-MCP) treatment (tx) on PSA dynamics in patients (pts) with nonmetastatic, biochemically relapsed prostate cancer (BRPC): Results of the interim analysis of a prospective phase II study.
Authors: Keizman Daniel , Frenkel Moshe A. , Edwards Todd Michael , Rosenbaum Eli , Margel David , Sarid David , Neiman Victoria , Gottfried Maya , Maimon Natalie , Leibovitch Ilan , Dresler Hadas , Eliaz Isaac
Published: September 2018

e16588

Background: 30% of pts with localized PC will have a biochemical relapse post local tx. The optimal tx of these pts remains elusive. While androgen deprivation therapy is effective in reducing PSA level, its long term benefit on survival remain undefined, and it is associated with significant cumulative toxicities.Thus evaluation of new non-toxic compounds in this pt population is warranted. P-MCP is a competitive inhibitor of galectin-3, a carbohydrate-binding protein, which is known to be involved in cancer pathogenesis. Preliminary pre-clinical and clinical data suggest that P-MCP is active in PC. We aimed to evaluate the safety and PSA dynamics of tx with P-MCP in pts with BRPC. Methods: Pts with non-castrate non metastatic BRPC were enrolled in a prospective phase 2 study of tx with oral P-MCP, at 4.8 grams X 3/day. Pts that did not progress clinically, biochemically (PSA), and radiologically, at 6 months (mos), were treated for subsequent 12 mos. Sample size provided 85% power to assess a decrease in PSA progression rate from 80% (natural history) to 40% (P-MCP tx) at 6 mos. We report here first results of a pre-planned interim analysis after ≤ 50% of planned enrolled pt completed 6 mos of tx. Results: The study was initiated in June 2013. We report here the 6 mos data of the first 35 pts enrolled. Median age was 74 years. Treatment of the primary tumor consisted of surgery in 11% (n = 4), radiation in 69% (n = 24), and both in 20% (n = 7). No pt had tx related grade 3/4 toxicity. One patient withdrew his consent after 1 mos. Of the 34 pts analysed, 18% (n = 6) had grade 1 toxicity. 62% (n = 21) had a stabilization/decrease of PSA, and negative scans, at 6 mo, and entered into the second 12 mos tx phase. A stabilization or improvement (increase) of PSA doubling time was noted in 79% (n = 27) of pts. Disease progression at 6 mos was noted in 38% (n = 13: PSA only 29%, n = 10; PSA and scans 9%, n = 3). A future final report will include full tx data (18 mos) and correlative analysis. Conclusions: The interim analysis of the present study suggests a potential benefit of P-MCP tx on progression of BRPC. P-MCP tx is safe. Final analysis is pending. Clinical trial information: NCT01681823.
Genetic diversity of HPV in tissues of tumors of the reproductive organs in women.
Authors: Nerodo Galina Andreevna , Kit Oleg Ivanovich , Zykova Tatiana , Ivanova Victoria A. , Nikitina Vera P. , Nerodo Ekaterina A. , Bogomolova Olga A. , Verenikina Ekaterina V. , Kravtsova Oksana E.
Published: September 2018

e17001

Background: The purpose of the study was to determine the rate of various HPV genotypes detection in tissues of tumors of the female reproductive organs. Methods: FFPE and frozen tissue samples of cervical cancer (n=126), vulvar cancer (n=113) and uterine cancer (n=29) were studied. DNAs of HPV 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58 and 59 were determined by the Real-Time PCR. Results: HPV DNAs were found in 94.4% of samples of cervical cancer tissue, 65.5% - uterine cancer tissue and 28.3% - vulvar cancer tissue. HPV 16 and 18 were the most frequent (78.8%). HPV 16 in cervical cancer was detected in 60.9%, vulvar cancer – 59.0% and uterine cancer – 54.5%. On the contrary, HPV 18 was more frequent in uterine cancer (40.9%) and less frequent in cervical cancer (18.4%) and vulvar cancer (2.7%). Besides HPV 16 and 18, genotypes 31, 33, 35, 39, 45, 51, 52, 56 and 59 were found in tumor tissues as well (21.2% in total). HPV 35, 52 and 56 were the most frequently detected. Cervical cancer tissues showed the greatest genetic diversity of HPV and uterine cancer tissues – the lesser one (HPV 35 only, besides HPV 16 and 18). Combination of several HPV types was also more frequent in cervical cancer (37.0% of positive samples); in vulvar cancer – 18.8% and in uterine cancer – 15.8%. Conclusions: The results confirm HPV significance in carcinogenesis of cervical cancer, vulvar cancer and probably uterine cancer and show genetic diversity of HPV in different localizations of tumors of the female reproductive system.
Dosimetric analysis of the effect of bladder volume on brachytherapy dose to organs at risk (OARs) in volume based intracavitary brachytherapy of carcinoma cervix: An institutional study.
Authors: Poddar Jyoti , Sharma Ashutosh Das , Suryanarayan K U , Shah Sonal Patel , Parikh Ankita
Published: September 2018

e17006

Background: External beam radiotherapy combined with intracavitary brachytherapy is the standard of care in Carcinoma cervix. Due to its characteristics of rapid dose fall off, brachytherapy limits the toxicity to organs at risk while escalating radiation dose to target. Still, the organs near the radioactive source are at risk of considerable exposure, toxicity and post treatment morbidity. Alteration of bladder volume, alters the relative anatomy of uterus, rectum, sigmoid colon causing changes in the radiation dose to these organs. Methods: Aim:To correlate between the bladder volume and its effects on the dose received by bladder, rectum and sigmoid colon in volume based HDR brachytherapy in carcinoma cervix.30 patients (78 Intracavitary Brachytherapy applications) of Carcinoma Cervix (FIGO stage II-III) treated with EBRT followed by volume based HDR brachytherapy at our institute between July 2014 to Jan 2016 were studied. Bladder volume data was tabulated into five groups according to increasing volume of bladder. It was correlated with D2cc dose received by bladder, rectum and sigmoid colon. Results: Statistical Analysis Linear regression and correlation analysisof the HRCTV with dose to the bladder was 0.2 (.i.e HRCTV does not influence the bladder dose.) Pearson correlation of bladder volume and D2cc bladder and D2cc rectum was positive for all groups and for sigmoid D2cc was positive for group B and negative for all other groups. P value = 0.064 Conclusions: Keeping the bladder volume low (<130 cc) during brachytherapy would reduce the dose to bladder and rectum and the probability of late bladder and rectal toxicity reduces. [Table: see text]
Inhibition of EGFR nuclear translocation attenuate radioresistance through decreased p-DNA-PK expression in cervical cancer cells.
Authors: Qi Yunxiang , Lang Jinyi , Li Lu , Feng Mei , Huang Yecai
Published: September 2018

e17011

Background: The commonly used treatment for cervical cancer is radiotherapy. However, the resistance to irradiation and metastasis at the advanced stage is a common reason for the poor prognosis and high mortality. This study was designed to elucidate the role of epidermal growth factor receptor (EGFR) nuclear translocation in radioresistance, and its correlation with DNA damage repair pathway in the cervical cancer cells. Methods: The dynamic expression of EGFR, DNA-dependent protein kinase (DNA-PK), PDK-1, PKN1 and their phosphorylation level in irradiated cervical cancer cell line CaSki at 0 10 20 40 minutes was determined by western blotting. Besides, nuclear localization signal (NLS) peptide inhibitor and control peptides was synthesized and treated cells before irradiation to elucidate the correlation between EGFR nuclear translocation and DNA damage repair after irradiation. Results: Expression of EGFR, protein kinase N1 (PKN1), and DNA-PK in nucleus was increased after irradiation in CaSki cells. Irradiation also enhanced the phosphorylation level of EGFR at Thr654, PKN1 at T774 and DNA-PK at T2609. Inhibition of EGFR nuclear translocation by NLS peptide decreased the expression level of EGFR and DNA-PK in the nucleus, and attenuated their phosphorylation process. Conclusions: EGFR nuclear translocation riggered by irradiation promoted DNA damage repair in irradiated cervical cancer cells. This work facilitated us to understand the possible molecular mechanism of the resistance to irradiation in the treatment of cervical cancer, providing a potentially potent clinical method to cancer therapy.
Therapeutic efficacy of epidermal growth factor receptor monoclonal antibody combined with concurrent chemoradiotherapy in treatment of locally advanced cervical cancer.
Authors: Chen Wenli , Li Tao , Zhang Wei , Yang Jialin , Wang Jian , Lang Jinyi
Published: September 2018

e17012

Background: There are few studies about epidermal growth factor receptor monoclonal antibody nimotuzumab for the treatment of locally advanced cervical cancer. We aimed to assess the therapeutic efficacy and analyse prognostic factors of chemoradiotherapy combined with nimotuzumab in cervical cancer (stage IIB-IVA) . Methods: We retrospectively analyzed 23 patients with locally advanced cervical cancer(stage IIB-IVA) ,who received concurrent chemoradiotherapy combined with nimotuzumab from 2012 to 2014 (the study group) ,and 30 patients with the similar baseline characteristics who received concurrent chemoradiotherapy alone (the control group). The overall response rates, 5-year overall survival rates, progression-free survival and acute adverse events of the two groups were compared .Multivariate prognostic analysis was performed by a Cox proportional hazards model. Results: The median follow-up time were 46 months (IQR 16-60) in the study group and 42 months (2-60) in the control group.The overall response rates were 87% and 73.3% (P = 0.384) . The 5-year overall survival rates were 63.6% and 36.1% (hazard ratio 2.208,95% CI 0.878-5.557,P = 0.092) .The median progression-free survival in the study group was not achieved (95%CI 9-55) versus 27 months (1-60) in the control group (hazard ratio 2.635, 95% CI 1.030-6.737, P= 0.043).Multivariate prognostic analysis indicated that stage and whether to be combined with nimotuzumab were the influential factors for progression-free survival time.Adverse events were similar between groups.The most common grade 3 or 4 adverse events during treatment in the study group versus the control group were leucopenia(9 [39%] vs 11 [36%]),thrombocytopenia (3 [13%] vs 6 [20%]),anaemia (4 [17%] vs 4 [13%]). Conclusions: Concurrent chemoradiotherapy combined with nimotuzumab in the treatment can improve the progression-free survival time of advanced cervical cancer, while not increasing the incidence of adverse reactions.However, because of the small size of sample in this research, these findings suggest that it is necessary to perform a prospective study with expanded sample size.
Comparative effectiveness of laparoscopic radical hysterectomy for cervical cancer.
Authors: Lee Jung-Yun , Kim Jae-Weon , Kim Kidong , Lim Myong Cheol , Kim Jin Hee
Published: September 2018

e17015

Background: Despite the benefits of minimally invasive surgery for cervical cancer, population-level data describing the surgery’s effectiveness in unselected patients are lacking. We compared morbidity, cost, and survival between abdominal radical hysterectomy and laparoscopic radical hysterectomy for cervical cancer. Methods: We used the Korean Health Insurance Review and Assessment Service database to identify women with cervical cancer who underwent radical hysterectomy from 2011 to 2014. Patient who underwent abdominal radical hysterectomy were compared with those who had minimally invasive hysterectomy. Perioperative morbidity, use of adjuvant therapy, and survival were evaluated. Results: We identified 6,335 patients including 3,235 who underwent abdominal radical hysterectomy and 3,100 who underwent laparoscopic radical hysterectomy. Uptake of laparoscopic radical hysterectomy increased from 46.1% in 2011 to 51.8% in 2014. Patients who were younger and treated at larger hospital were more likely to undergo laparoscopic procedure (P<0.001). Laparoscopic radical hysterectomy had lower rates of complication, less transfusion requirement, shorter hospital stays, and reduced total medical costs (P<0.001). There was no significant association between use of laparoscopic approach and recurrence-free survival (P=0.194). Conclusions: Laparoscopic radical hysterectomy was associated with lower risk of perioperative complication and have comparable outcomes with abdominal radical hysterectomy.
Impact of vascular endothelial growth factor (VEGF) and hypoxia-inductible factor-1 alpha (HIF-1) expression on the prognosis of locally advanced cervical carcinoma (LACC) treated with radiochemotherapy.
Authors: Madani Julia , Eizaguirre Beatriz , Alonso Vicente , Puertolas Teresa , Millastre Esther , Polo Marques Eduardo , Lao Romera Juan , Herrero Ana , Anton Antonio
Published: September 2018

e17023

Background: Combination of radiotherapy plus platinum-based chemotherapy (RT-CT) is considered the standard treatment in LACC. The risk of recurrence after local treatment is around 50-70%. The role of angiogenesis in tumor progression has been shown in large series. The aim of this study was to determinate the impact of the expression of VEGF and HIF-1 on disease-free survival (DFS) and overall survival (OS) in patients with LACC receiving RT-CT. Methods: Expression of VEGF and HIF–1 was assessed by an immunohistochemistry (IHC) assay in 115 cases. Inmunostainning was considered negative (< 10% of cells), slightly positive (< 25%), moderate (26%-50%) and strongly positive (> 50%). A univariate analysis was carried out for each variable using the log-rank test. Subsequently, a multivariate analysis was performed employing Cox’s proportional hazards model. Results: 115 patients (p) with LACC were included and received RT-CT between January/2003 and December/2012. IHC revealed absence of expression of VEGF in 12 (10,4%) cases, slightly positive in 34 (29,6%), moderate in 30 (26,1%) and strongly positive in 39 (33,9%). The expression of HIF-1 was negative in 63 (54,8%) cases and positive (weak or moderate) in 52 (45,2%). 76p (66,1%) showed a complete clinical response (CR), 26p (22,6%) partial response and 13p (11,3%) stable disease or progression. The median follow–up was 35 months (1-140). 56p (48,7%) relapsed. Univariate analysis indicate that ECOG > 1, tumor size ≥ 4,5 cm, FIGO stage III-IVA, lymph nodes positive, non CR, CA125 post-treatment ≥ 35 U/mL, hemoglobin levels <11 mg/dl (basal, nadir and post-treatment), strong expression VEGF and positive expression of HIF – 1 were all associated with a significant lower OS and DFS. In multivariate analysis strong expression of VEGF remained statistically significant, as tumor size, non CR and hemoglobin level post-treatment < 11g/dL. Conclusions: IHC-assessed strong expression of VEGF was independent prognostic factor of shorter OS and DFS in patients with LACC treated with RT-CT. IHC determination of VEGF could be useful in clinical practice.
Clinical effect of liver transaminase abnormalities after ablation of ovarian cancer.
Authors: Manahan Kelly J , Geisler John P.
Published: September 2018

e17042

Background: At initial presentation, patients with ovarian cancer often have disease involving the upper abdomen and specifically the liver (surface or parenchyma). The object of this study was to 1) see the difference in liver enzyme levels in women getting tumor ablation involving the liver compared to women getting tumor ablation not involving the liver and to 2) see if any differences had a readily noticeable clinical effect. Methods: A series of twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction with tumor ablation involving the liver were compared to twenty women with initial diagnosis of ovarian cancer undergoing primary cytoreduction and tumor ablation without involvement of the liver. The data were compared with Fisher’s exact, Chi-square or Mann-Whitney U as appropriate. Results: Women undergoing tumor ablation involving the liver compared with women undergoing tumor ablation not involving the liver had significantly elevated AST and ALT levels the first day after surgery (p = 0.002; 0.002, respectively). There were no significant differences in age, operative blood loss or need for transfusion (p=0.24; 0.065; 0.33, respectively). The mean time for resolution of the elevations of AST and ALT was 2.5 days (95% CI = 1.8-3.2) for AST and 2.8 days (95% CI = 2.0 -3.6) for ALT. Conclusions:Significant elevations in AST and ALT occur when tumor involving the liver is ablated in women undergoing debulking for ovarian cancer. This elevation does not appear to increase operative blood loss or need for transfusion.
Perioperative positioning management in gynecologic cancer surgery: A national NOGGO-AGO intergroup survey.
Authors: Sporkmann Mareike , Wagner Jenny Katharina , Richter Rolf , Burges Alexander , Schmalfeldt Barbara , Veldink Hendrik , Schrettenbrunner Irmela , Pietzner Klaus , Sehouli Jalid
Published: September 2018

e17046

Background: Perioperative positioning injuries occur in approximately 4% of all medical complications. The aim of the present survey was the analysis of positioning-management in gynecologic-oncological surgery, the process- and structure-reliability and the implementation of current guidelines into daily clinical practice. Methods: A multiple-choice anonymous questionnaire about the perioperative positioning management in gynecologic oncology was sent to all gynecological departments in Germany. Sixty questions were divided into five different parts: 1) descriptive information about the department, 2) focus on the pre- and 3) postoperative management, 4) on the quality management, and 5) information regarding the management of positioning in the operation room based on two fictional case examples in gynecologic oncology procedures. Results: 184 of 633 departments participated in the survey between June and September 2016. Complications related to intraoperative positioning occurred in 48.4% of all participating departments, independent from department size. Knowledge of the current guideline on positioning did not impact the incidence of complications. The positioning of the patient was mentioned in the team-time-out procedure in 66.1% of the participating departments. No difference was found between high-volume and low-volume gynecologic oncologic operative departments with regard to the use of supportive tools such as anti-thrombotic leg pumps. The vast majority with 92.7% included information of positioning injuries into the written informed consent. Knowledge of the guideline or a previous legal dispute did not influence the willingness to inform about possible positioning-related complications. Conclusions: Our survey shows, that the awareness of perioperative positioning management in gynecologic cancer surgery is high throughout all sizes departments in Germany. Almost half of all 184 participating departments report positioning-related complications in the previous 12 months, stressing the importance of this often underrated topic.
Reactive oxygen species in patients with ovarian adenocarcinoma treated with platinum based chemotherapy.
Authors: Rodica Maricela Anghel , Gales Laurentia , Gruia Maria Iuliana , Trifanescu Raluca Alexandra , Curea Fabiana , Botnariuc Inga , Trifanescu Oana
Published: September 2018

e17047

Background: Ovarian adenocarcinoma (OA) is the most lethal of gynecologic tumors because women generally present with advanced stage disease. Platinum-based chemotherapy plays a pivotal role in OA treatment. The aim of the study was to assess the role of oxygen species in patients with OA and the effects of platinum based chemotherapy on blood redox status. Methods: Twenty three patients with advanced stage IIIC or IV OA who underwent platinum salts chemotherapy were included. Blood sample were collected before treatment, at 21 days (second cycle of chemotherapy) and at 42 days (3rd cycle) and at 63 day (4th cycle) with a platinum salt (cisplatin or carboplatin). Biochemical determination of oxidative stress was made by mesuring lipid peroxidation index (LPI), the enzymatic activity of ceruloplasmin and the thiol albumin groups. Results: Median age at diagnosis was 52 years, and 47.8% of patients presented with stage IIIC and 52.2% with stage IV. Nine patients received for the first time platinum based chemotherapy and 14 received multiple lines of chemotherapy. Response rate after 4 cycles were partial in 30%, stable disease in 57%, and progression disease in 13%. Mean value (± SD) of lipid peroxides was 6.81±1.μmol/100 ml (normal value 0-4), and of ceruloplasmin 156 ± 66 UI (normal value 80-120) which showed an increase of the final products of lipid peroxidation. Thiol mean value was 296±124 μmol/l (normal value 370- 450). The evolution of these reactive oxygen species were monitored during chemotherapy cycles. Decrease of the lipid peroxidation after 1st cycle was noticed, (7, 6.89, 5.87, 6.61), because platinum salt can bind peroxyde and this can be considered a marker of effectiveness of treatment.The thiol levels increased from one cycle to other (233, 311, 384, 393) showing that the cell is trying to contracarete the oxidative stress. Conclusions: Tumors produces reactive oxygen species in excess in patients with advanced OA. Platinum based chemotherapy in patients with OA induces radical formation and the dynamic of these markers may be used to monitor response to treatment.
Testing of BRCA 1/2 gene mutations in FFPE samples of patients with high-grade serous ovarian cancer and limits of its bioinformatic interpretation.
Authors: Janikova Katarina , Lasabova Zora , Grendar Marian , Farkasova Anna , Scheerova Karla , Slavik Pavol , Vanova Barbora , Zelinova Katarina , Jagelkova Marianna , Plank Lukas
Published: September 2018

e17060

Background: BRCA1/2 mutations represent first genetically defined predictive markers for targeted therapy of patients with recurrent high-grade serous carcinoma (HGSC), therefore patients with HGSC should be tested for a germline and somatic BRCA mutation (g BRCAm and s BRCAm, resp.). In our study we analyzed possibilities and limits for determination of both origin and pathogenicity of mutations detected by HGSC biopsies analyses. Methods: We present data obtained by massive parallel sequencing on Miseq (Illumina). Library for sequencing was prepared by Somatic BRCA Tumor MASTR Plus kit (Multiplicom) from DNA isolated from HGSC FFPE tissue of 42 patients allowing simultaneous identification of g BRCAm and s BRCAm. For the pathogenicity evaluations we followed American College of Medical Genetics and Genomics (ACMG) criteria and used various bioinformatic tools. Results: All sequencing data were interpreted by SOPHIA DDM (Sophia Genetics) commercial tool. BRCA1/2 mutation was absent in 43% and present in 50% of patients, while 7% of cases had to be retested due to low coverage. Data of 28/42 patients were analyzed also by Ingenuity (Qiagen), the comparison of both the tools identified discrepant pathogenic determinationin 29% of them. The discrepancies in origin and pathogenicity of already detected mutations were found also by analyzing the data in other non-commercial databases (dbSNP, COSMIC, ClinVar, BIC, etc.). Conclusions: At least in a certain proportion of the cases, the data obtained by HGSC biopsy specimen mutational analyses and interpreted by accessible bioinformatic tools may lead to an equivocal assessment of both origin and pathogenicity of detected BRCA1/2 mutations. Other studies are necessary to eliminate the observed discrepancies.
VEGF-А in regulation of vascular endothelium functions and ascitic fluid production in ovarian cancer.
Authors: Moiseenko Tatiana , Frantsiyants Elena Mikhaylovna , Cheryarina Natalia D. , Pogorelova Yulia A. , Kozlova Larisa , Tkalya Lyudmila Dmitriyevna , Kravtsova Oksana E. , Adamyan Meri Viktorovich , Chalabova Tatiyana Georgievna , Kit Oleg I.
Published: September 2018

e17067

Background: Our purpose was to study VEGF-A, VEGF-R1, VEGF-C and FGF21 in the blood serum (BS) and ascitic fluid (AF) in stage I-IV ovarian cancer. Methods: BS in serous cystadenocarcinoma (CAC, n=76) and cystadenoma (CA, n=47) was studied. Histological control was performed in all cases. The data were compared to BS in uterine myoma (UM, n=20) and in 36 healthy donors (N), all women aged 51.5±2.6 years. Native AF was studied in patients with CAC affecting one ovary without treatment (n=26, T3-4N0M0) and ovarian CA (n=12). Levels of VEGF-А, VEGF-R1, VEGF-С and FGF21 were measured by ELISA. Results: Levels of VEGF-A in CA BS exceeded N by 1.8, sVEGF-R1 – by 2, VEGF-C – by 1.7 and FGF21 – by 2.6 times. VEGF-A in T1N0M0 CAC exceeded N and CA by 2.9 and 1.6, in T2N0M0 – by 3.1 and 1.7, in T3NxM0 – by 5.5 and 3, in T4Nx-1M0 – by 5.8 and 3.1 times. sVEGF-R1 was similar in all CAC stages, on average twice higher than N, and similar to CA and UM. Differences were found between VEGF-А in CAC, CA and UM. sVEGF-R1 in all BS exceeded N (Р˂0.05 in all cases). VEGF-С in CA and UM BS exceeded N on average by 1.7 times, and in CAC it was significantly higher than in CA, UM and N. VEGF-С in BS in T1N0M0 was higher than in N and CA by 2.0 and 1.2, in T2N0M0 – by 2.6 and 1.6, in T3NxM0 – by 2.5 and 1.5, in T4Nx-1M0 – by 2.5 and 1.5 times, respectively. Differences in VEGF-С were found only in T1N0M0 and T2N0M0 by 1.3 times (Р˂0.05 in all cases). FGF21 in BS in UM and CA was similar, but differed from N by 2.6 times. FGF21 in all CAC stages exceeded BS and CA by 4 and 1.5 times. VEGF-А in CAC AF exceeded CA by 9.8, sVEGF-R1 – by 3.9; VEGF-C – by 1.6; FGF21 – by 1.7 times. VEGF-А, sVEGF-R1, FGF21 and VEGF-А/sVEGF-R1 in AF in UM and CA were similar to BS, and VEGF-С was lower than in BS by 1.7 times (Р˂0.05 in all cases). VEGF-А and sVEGF-R1 in BS in CAC were higher than in N by 2.9-5.8 and 2 times; in AF – higher than in UM by 9.9 and 4 times. VEGF-С in AF in CAC was lower than in BS on average by 1.6 times (Р˂0.05), and FGF21 did not differed in AF and BS. Conclusions: VEGF in SВ correlates with CAC stages distinguishing early and later ones. VEGF-А is higher than VEGF-C in BS and AF in all tumors. The VEGF family regulates functions of the endothelium of lymphatic and blood vasculature influencing oncogenesis and the occurrence of ascites.