bluuebunny/crossref_metadata_2025 huggingface dataset:
U.K. experience of sunitinib malate in the treatment of metastatic renal cell carcinoma: Predictors of response from clinical practice.
Authors: Goranova Rebecca Allison , Goranov Bojidar Bojidarov , Pedley Ian David , Azzabi Ashraf , Humphreys Alison , McMenemin Rhona , Frew John A.
Published: February 2017

455

Background: Sunitinib gained NICE approval in March 2009 as first line treatment for metastatic renal cell carcinoma (mRCC) and UK experience of use of Sunitinib is growing. The North of England Cancer Network (NECN) was the first cancer network in the UK to approve the use of Sunitinib in July 2007 and has the longest UK experience with this drug. The clinical outcomes of the NECN patients are presented.

Methods: Data was collected and analysed regarding all patients started on Sunitinib from 01/07/2007 to 30/09/2010. Follow up extended to 28/02/2011. Previously published predictors of response were compared to the NECN data to check applicability in this population.

Results: 129 patients were identified with a median age of 63 years (range 21-87), 67% were male and WHO performance status was 0, 1 or 2 (33%, 51%, 16%). 80% of patients had nephrectomy (60% radical) and 22% had prior systemic treatment. Median PFS was 10 months (range 0.25-27). Median OS (from Sunitinib initiation) was 17 months (range 0.25 - 47). Performance status was significantly associated with PFS and OS. The median number of treatment cycles was 5 (range 0.25-27). 64% of patients were dose reduced and 9% had a schedule modification to minimise toxicity. 21% of patients had a delay of 4 weeks or more which was not detrimental to median PFS. Dose reduction at treatment initiation was associated with a significant decrease in OS. 11.6% of patients required treatment for hypothyroidism which was associated with a significant improvement in PFS and OS. 15.5% of patients required treatment for hypertension, which was associated with an improvement in OS, but not PFS.

Conclusions: PFS in the NECN population is similar to trial data. Strategies to deal with side effects, including dose reduction (after treatment initiation), treatment delay and schedule changes, did not adversely affect PFS. Performance status 0, the development of new hypertension or new hypothyroidism can be regarded as markers of good prognosis in this population. Initial dose reduction should be avoided as this adversely affects prognosis.
Percutaneous and laparoscopic-assisted cryoablation of small renal cell carcinomas.
Authors: Nielsen Tommy Kjaergaard , Ostraat Oyvind , Borre Michael , Johansen Truls E Bjerklund
Published: February 2017

462

Background: To evaluate the complication rate and short term oncological outcome of small renal cell carcinomas treated with cryoablation.

Methods: 91 biopsy verified renal cell carcinomas were cryoablated between 2006-11. Patients treated had primarily T1a tumors, but exceptions were made. Patients with tumors not directly accessible percutaneously were selected for laparoscopy. To ensure complete coverage of the tumor, cryoneedle placement and freezing procedure was peroperatively monitored by ultrasound in both modalities. Presice machine with Ice-Seet and Ice-Rod needles from Galil Medical was used. Treatment was considered successful when tumors gradually shrunk and showed no sign of contrast enhancement, assessed by CT or MRI.

Results: Mean patient age and tumor size was 65 yr [17 - 83] and 26 mm [10 - 62], respectively [min-max]. Treatment modalities consisted of percutaneous route; n=34 (47%) and laparoscopic guided; n=39 (53%). The mean follow-up time was 19 months [1 - 56]. 18 patients were excluded from follow-up analysis (8 pt. with short observation time, 5 pt. treated despite severe co-morbidity with no planned follow-up, 3 pt. lost to follow-up, 1 pt. emigrated, 1 pt. died as a result of bleeding from perforation of iliac artery by troicar). Residual tumor was diagnosed by imaging in 10 patients (perc n=6 and lap n=4, p>0,05) after a mean follow-up time of 13 months [1 - 31]. Diagnosis was confirmed by biopsy in all but one case, in which the diagnosis was necrosis. Of the 10 patients with residual tumor, 8 patients were reablated and 2 patients were referred to oncological treatment. Cancer specific survival was 100%. Overall survival was 91%. Complications: 8 pt. had minor bleeding in relation to cryoneedle removal, requiring Tachosil. 1 pt. had subcutaneous bleeding, 2 pt. was readmitted due to pain and discharged the following day. No patients required blood transfusion.

Conclusions: Although percutaneous and laparoscopic guided cryoablation are minimally invasive procedures and the overall complication rate is low, serious complications may occur. Close follow-up and continuous evaluation of criteria for patient selection and relapse is necessary. An international database is recommended.
Detection of prostate cancer with histoscanning: A retrospective analysis in 85 patients.
Authors: Epplen Robin , van Essen Julius , van Erps Thomas , Porres Daniel , Pfister David J. K. P. , Heidenreich Axel
Published: February 2017

53

Background: HistoScanning is a tissue differentiation and visualization tool which identifies changes to solid organ tissues. It uses a specific three dimensional transrectal ultrasound device to acquire and transmit data to a software program. Data is processed and suspicious areas in the prostate are projected in 3D. Our objective was to compare HistoScanning with histopathology of radical prostatectomy specimens and to determine sensitivity regarding the detection of cancer volume and localization.

Methods: We analyzed the preoperative results of histoscanning in 85 men underwent radical prostatectomy. All prostatectomy specimens were processed according to the Stanford protocol by an experienced uro-pathologist.Results were correlated with final pathology according to localisation and volume. A match was defined as a HistoScan positive lesion in a correspondent histopathologically positive area.Results were analyzed according to pT-stadium, GS, PSA, cancerous tissue volume and volume of HistoScanning-lesions.

Results: Mean patients’ age was 62,8 yrs, PSA 11.83ng/ml, prostate volume was 47,5 ml and mean tumor volume was 4,80ml. 44 patients had a pT2 tumor, 38 had a pT3 carcinoma (3 pts pT4). 8 pts had salvage prostatectomy. 9 patients had GS of 6,50 and 18 pts had GS 7 and GS ≥8 respectively. HistoScanning had 74% overall sensitivity.Sensitivity was higher for pT3 tumors (92%) than for pT2 carcinoma (61,36%). HistoScanning detected (5/9=55%) of GS 6, (37/50= 74%) of GS 7 and 15/18=83% of GS ≥8 carcinoma. Preoperative PSA had no statistical significance. HistoScanning detected small tumors (<1 ml) in 50%, intermediate (1-5ml) in 57,5% and large(>5ml) in 86% respectively. Identical results are seen regarding the volume of suspicious lesions. For small (≤0,5 ml), intermediate (0,5-2ml) and large (>2ml) lesions, it correctly predicted prostate cancer localisatio 33%, 78,5% and 64,7%, respectively.

Conclusions: HistoScanning seems to have a great potential in the detection of significant prostate cancer. In particular, extracapsular, poor differentiated and large prostate cancers show a high detection rate. However, larger prospective studies are needed to verify these preliminary results.
Evaluation of circulating tumor cells (CTCs) enumeration and 18F-Choline positron emission tomography/computed tomography (FCH PET/CT) as early efficacy response biomarkers in metastatic castration-resistant prostate cancer (CRPC) patients (pts) treated with abiraterone acetate.
Authors: Le Moulec Sylvestre , Massard Christophe , Gontier Eric , Farace Françoise , Chargari Cyrus , Vielh Philippe , Aupee Olivier , Vedrine Lionel , Foehrenbach Herve , Fizazi Karim
Published: February 2017

63

Background: Circulating tumor cells (CTCs) and FCH PET/CT are both promising tools for treatment monitoring in CRPC pts. In this study, we assessed prostate specific antigen (PSA), CTC and FCH PET/CT for monitoring treatment response in metastatic CRPC pts receiving recently approved abiraterone acetate therapy after chemotherapy.

Methods: Twenty nine metastatic CRPC pts progressing after docetaxel chemotherapy received abiraterone acetate 1,000 mg daily with prednisone 5 mg twice daily in continuous 28-day cycles. Pts were evaluated monthly for efficacy and safety. CTCs counts (using the CellSearch assay) and FCH PET/CT were performed at baseline and at 4 weeks (PERCIST criteria and SUV Peak).

Results: After one month of treatment, 12 pts (41%) had a PSA rise and 17 pts (59%) had a PSA decline. At baseline, 18 pts had detectable CTCs (at least 5 CTCs), and 6 of them (33%) had a decline from at least 5 to less than 5 CTCs after 4 weeks of treatment. 10 of 29 pts (34%) had a > or = 30% decline in CTCs. Amongst 22 pts who were evaluable by FCH PET/CT, response assessment was as follows: response (n=8), stable disease (n=12), progression (n=1). PSA decline and CTCs levels correlated in 16 of 29 pts (55%), and were discordant in 13 of 29 pts (45%). In all 12/29 pts (41%) with a 50% or more decline in PSA both a CTCs response and a FCH PET/CT response was observed. In patients with a PSA rise while on abiraterone acetate, 8 pts did not have a CTCs increase or a CTC conversion from unfavourable to favorable, and 7 of 8 pts had a PSA decline at 3 months or a FCH PET/CT response. No flare phenomenon on FCH PET/CT was observed.

Conclusions: Monitoring pts with CRPC who receive abiraterone using both CTCs and metabolic imaging indicate discrepancy in 45% with response assessment using PSA. Association between CTC drop, early FCH PET/CT response and clinical benefit is currently under study.
The influence of growth hormone/insulin-like growth factor deficiency on prostatic dysplasia in pbARR2-cre PTEN knockout mice.
Authors: Ibuki Naokazu , Takahara Kiyoshi , Gaffari Mazyar , Tearle Howard , Ong Christopher J. , Pollak Michael N. , Gleave Martin E. , Cox MIchael E.
Published: February 2017

66

Background: Signaling through GH/IGF-I axis has been linked to PCa risk. The GH/IGF-I axis is an important regulator of growth, survival, and metastatic potential in a variety of malignancies and is strongly implicated in PCa etiology. A range of therapeutic approaches including reducing ligand availability by GH antagonist, IGF-I antibodies, and recombinant IGFBPs, reducing IGF-1R expression by antisense and RNA interference, or inhibiting of IGF-1R signaling by IGF-1R antibodies and small molecule tyrosine kinase inhibitors are under investigation in PCa.

Methods: To investigate the role of GH/IGF-I axis on in vivo prostate carcinogenesis and neoplastic progression, we crossed pbARR2-Cre, PTEN(fl/fl) mice (PTEN-/-) with IGF-I deficient lit mice, and produced lit/lit and lit/+ PTEN-/- mice. To complement the in vivo experiments, in vitro growth and growth factor signaling of murine PTEN-/- cells derived from the prostate (MPPK) using serum from lit/lit or lit/+ mice was examined.

Results: No obvious differences in prostatic dysplasia were observed in lit/lit mice at 15 and 20 weeks of age when compared to lit/+ littermates measured as normalized prostatic wet weight or for expression of the murine prostatic differentiation markers, probasin and PSP94. However the rate of decreased expression of E-cadherin and increased expression of N-cadherin was slightly delayed in PTEN-/- prostates from lit/lit mice as compare to lit/+ mice. In vitro, growth of MPPK cells was decreased when cultured in serum from lit/lit mice as compared with serum from lit/+ mice. Suppressed growth of MPPK cells in lit/lit serum could be restored by addition of IGF-I, and to a lesser extent, GH. Addition of GH or IGF-I to lit/lit serum increased steady-state activation of AKT without affecting ERK1/2 activation.

Conclusions: Our data suggest that initiation of prostate carcinogenesis by loss of PTEN is not influenced by germ line variation of genes encoding signaling molecules in the GH/IGF-I axis, but suggests that such factors may affect the progression of dysplasic phenotype.
Prediction of favorable outcome in a docetaxel rechallenge setting in metastatic castration-resistant prostate cancer.
Authors: Heck Matthias Michael , Thalgott Mark K. , Retz Margitta , Wolf Petra , Maurer Tobias , Gschwend Juergen , Kuebler Hubert
Published: February 2017

68

Background: To identify predictors of favourable oncological outcome in metastatic castration-resistant prostate cancer (mCRPC) patients who are treated with docetaxel rechallenge following first-line chemotherapy with docetaxel.

Methods: We retrospectively evaluated the oncological outcome of mCRPC patients who were treated with 3-weekly docetaxel (75mg/m2) at first-line chemotherapy and rechallenge plus prednisone/ prednisolone. The endpoints of oncological outcome were PSA-progression-free survival (PSA-PFS) and overall survival (OS) after initiation of docetaxel rechallenge. The effect of clinical variables on PSA-PFS and OS was statistically analysed by a log-rank test or Cox regression with hazard ratios. All analyses were performed using a 0.05 level of significance.

Results: 47 patients were included on analysis. At a median follow-up of 25.8 months (range 9.8-89.8 months) after the first administration of docetaxel, 27 (57.4%) patients had died. Median PSA-PFS was 5.9 months (95% CI 3.5-6.8 months) and median OS was 21.4 months (95% CI 18.9-23.9 months) after initiation of docetaxel rechallenge. PSA-reduction ≥ 30% was the only pre-treatment variable that correlated significantly with prolonged PSA-PFS (p=0.03) and OS (p=0.002). Patients with PSA-reduction ≥ 30% at first-line chemotherapy showed a median OS of 21.8 months since initiation of docetaxel rechallenge in comparison to 4.5 months in patients with < 30% PSA-reduction.

Conclusions: Docetaxel rechallenge represents an active treatment option in selected docetaxel-pretreated patients with mCRPC. In this retrospective study, PSA-reduction ≥ 30% at first-line chemotherapy with docetaxel predicted superior PSA-PFS and OS in the rechallenge setting and might, therefore, present a rational indication for docetaxel rechallenge.
The prostate cancer survivorship program: A new concept for holistic long-term support and follow-up.
Authors: Goonewardene Sanchia Shanika , Young Annie , Symons Mary , Sullivan Anne , McCormack Gary , Milner Vanessa , Makar Adel
Published: February 2017

72

Background: Previously cancer follow-up was based in secondary care. Survivors were seen in overburdened clinics, receiving brief clinic appointments and limited holistic care. We have piloted a new community based model in prostate cancer survivors in order to reduce service load. Patients are discharged from clinic, and entered into a specially developed web based database. This reviews PSA results, triggers alerts, resulting in specialist nurses (CNS) bringing patients back to clinic. This is supplemented by an annual survivorship conference, where patients have access to heathcare professionals. Patients also have access to community based services including a newly built community centre for patients where they have access to a range of healthcare professionals, ranging from dieticians to psychologists. We present our results, and evaluate this model independently with Pickering Institute patient questionnaires distributed one month pre and post conference and focus groups to develop further recommendations for the programme.

Methods: We have developed a team composed of a consultant urological lead, commissioners, a GP, a specialist nurse, patient representatives and an IT specialist. Patients were entered into this programme over the past 1 year (323 so far). Inclusion criteria specify patients must be: 2 years post radical prostatectomy (unrecordable PSA), 3 years post radical radiotherapy with/ without hormones or 3 years post brachytherapy (both with stable PSA) according to the Phoenix criteria.

Results: Patients completed an outcome questionnaire before the conference and one month afterwards (55 in total). Perceived control pre-conference was 7.19, post conference 7.38. Concern pre-conference was 3.56, 3.46 post conference. Understanding pre-conference was 7.49, 7.85 post-conference. Focus Group Results: The advantages of community based follow up were having an approachable primary contact, speedy referral, saving time, money and stress over prolonged waits and brief hospital appointments.

Conclusions: We discuss how the programme can be developed, including: PSA feedback, a buddying system, and how this can be put into use across other tumour sites and other specialities.
Effect of open versus robot-assisted laparoscopic radical prostatectomy on cancer control in patients with clinically localized prostate cancer: Prospective analysis of 1,014 consecutive patients.
Authors: Fairey Adrian Stuart , Jacobsen Niels , Voaklander Don , Estey Eric
Published: February 2017

80

Background: There are limited prospective data comparing outcomes of Open Radical Prostatectomy (ORP) and Robot-Assisted Laparoscopic Radical Prostatectomy (RALRP) for clinically localized prostate cancer. Our aim was to compare ORP and RALRP with respect to cancer control outcomes.

Methods: A prospective analysis of data from the University of Alberta Radical Prostatectomy Database was performed. Between September 2007 and August 2010, 1019 consecutive men underwent radical prostatectomy for clinically localized prostate cancer. The surgical approach was selected by the surgeon. The outcomes were biochemical recurrence (BCR) and positive surgical margins (PSM). BCR was defined as a PSA ≥ 0.1 ng/ml followed by a subsequent confirmatory value or initiation of salvage therapy. PSM was defined as the presence of cancer at the inked margin in the radical prostatectomy specimen. The Kaplan-Meier method was used to estimate biochemical recurrence free survival (BCRFS). Univariable and multivariable analyses were used to determine the association between surgical approach and outcomes.

Results: Data were evaluable for 1014 out of 1019 patients. 204 patients underwent ORP and 810 patients underwent RALRP. The median follow-up duration was 21 months (IQR 12 to 29). Baseline characteristics were similar between the groups. In univariable analysis, 3-year BCRFS (90.6% versus 88.9%), overall PSM (26.5% versus 28.8%), and stage-stratified PSM (pT2: 19.9% versus 21.8%; pT3: 40.6% versus 49.1%) did not differ between the groups (all comparisons p>0.05). In multivariable analysis, surgical approach was not independently associated with BCR (HR 0.77, 95% CI 0.43 to 1.37, p=0.37) or PSM (OR 1.2, 95% CI 0.80 to 1.67, p=0.44).

Conclusions: ORP and RALRP provided comparable short-term oncologic efficacy. Extended follow-up of the prospective cohort is needed to confirm these preliminary findings.
The safety of prostate biopsy procedures in the research setting: A 10-year multicenter experience.
Authors: Tadros Nicholas N. , Farris Paige E. , Shannon Jackilen , Beer Tomasz M. , Garzotto Mark
Published: February 2017

87

Background: The safety of routine prostate biopsies has recently been called into question, citing increasing rates of complications compared to historical data. We examined our experience with prostate biopsies done as a component of multiple clinical research trials.

Methods: The safety of routine prostate biopsies has recently been called into question, citing increasing rates of complications compared to historical data. We examined our experience with prostate biopsies done as a component of multiple clinical research trials.

Results: 141 charts had adequate documentation. A mean of 12 +/- 4 cores were obtained during the procedures (8-26). Of these patients, 136 of the 141 had no adverse events during or after their biopsies. Of the five adverse events, there were three (2.2%) minor and two (1.4%) major complications. The minor complication group consisted of three patients with mild, but prolonged hematuria (12-14 days). Of the two major complications, one patient had hematospermia for 28 days and the second patient was diagnosed with prostatitis 18 days after biopsy and required multiple antibiotics. No patient required any further intentions or hospitalizations. There was no correlation between complication rate and study type (p=0.662) or treatment setting (p=0.411). Overall, 96.5% of patients undergoing prostate biopsies for research purposes had no adverse events or complications related to the procedure.

Conclusions: Research related prostate biopsy procedures can be performed in a diverse range of treatment settings and do not incur any increased risk versus clinical biopsies.
A phase II study of atorvastatin and celecoxib in patients with rising PSA following local therapy for prostate cancer (PC).
Authors: Goodin Susan , Stein Mark N. , Shih Weichung , Lu Shou-En , Zheng Xi , Anand Monica , Jeyamohan Chandrika , Mayer Tina M. , Somer Robert A. , Heath Elisabeth , Conney Allan , DiPaola Robert S.
Published: February 2017

89

Background: Single agent atorvastatin and celecoxib have been associated with reductions in the risk of PC. Our laboratories have demonstrated that low doses of the drug combination have synergistic effects inhibiting the progression of LNCaP tumors to androgen independence. We therefore sought to determine the effects of the combination in androgen-dependent PC on PSA kinetics and the plasma correlates of IL-6, C-reactive protein (CRP), PGE-2, and the pharmacokinetics of the drug combination to validate preclinical biomarker findings.

Methods: Patients with rising PSA after primary therapy for PC were enrolled. Patient must have three rising PSA values, each obtained at least 1 month apart. No prior hormone-ablative therapy was allowed, except in the neoadjuvant setting or in the setting of salvage XRT completed 3 months prior to enrollment. Patients with any history of coronary artery disease or a previous myocardial infarction in the past 6 months were excluded. All patients were treated with atorvastatin 20 mg daily and celecoxib 200 mg twice a day for 6 months. Paired pre-treatment and on treatment PSA kinetics were compared using the Wilcoxon Signed Rank test.

Results: We report on 14 patients that have completed therapy. Median pretreatment PSA slope was 0.14 log PSA/mo (median PSADT 4.98 mos), in contrast to the median on treatment slope of 0.09 log PSA/mo (median PSADT 7.37 mos); p=0.11. Eleven of the fourteen patients completed the 6 months of therapy, 1 patient withdrew and 2 patients therapy was stopped early due to lack of response. A declining PSA was observed in one patient. The combination was well tolerated, with no clinically significant therapy related toxicities ( > grade 1) reported in 76 months of therapy.

Conclusions: In this ongoing phase II trial, the combination of low dose atorvastatin and celecoxib has been well tolerated and demonstrates a tendency of increasing PSA doubling time. Enrollment continues with analysis of IL-6, CRP, and PGE-2 to be correlated to individual clinical results.
Frequency and prognostic significance of the PSA flare-up phenomenon in men with castration-resistant prostate cancer (CRPC) who undergo docetaxel-based chemotherapy.
Authors: Piper Charlotte , van Erps Thomas , Pfister David J. K. P. , Epplen Robin , Porres Daniel , Heidenreich Axel
Published: February 2017

92

Background: Chemotherapy with docetaxel and prednisone represents the guideline-recommended first-line therapy in men with metastatic CRPC. Until now there is a lack of information with regard to the oncological efficacy, survival and treatment-associated toxicity in patients who are treated in the community beside clinical trials.

Methods: 487 patients were prospectively recruited according to a standardized questionnaire within a 1-year time interval. Patients were treated in 144 institutions who contributed between 2 and 48 patients. The mean age was 73.4 (41 – 85) years, the mean PSA level was 135.9 (2.1 – 1.895) ng/ml. 445 (91.5%) patients had bone metastases and/or lymph node metastases. Cardiovascular, pulmonary, neurological or endocrinological comorbidities were present in 157 (27.5%) patients.

Results: The mean follow-up was 24 (15-36) months. A mean of 6.6 (1-21) cycles docetaxel were delivered. 101 (20.7%) patients received 1-3 cycles, 222 (45.6%) patients received 4-6 cycles and 167 (34.3%) patients underwent 7-10 cycles. 29 (5.9%) and 295 (61.4%) patients achieved a complete or partial remission, respectively; 95 (19.5%) and 19 (3.9%) patients demonstrated stable disease or progression, respectively. An immediate, delayed (flare-up) or no PSA response was achieved in 40.9%, 29.9% and. 21.8%, respectively. During follow-up 192 (40.6%) patients developed progressive disease. 49 (10.4%) patients died, 37 (7.8%) died due to cancer progression. The mean and median progression-free survival was 256.6 ± 14.8 and 216 days, respectively. The mean and median overall survival was 394 ± 10.7 and 476 days, respectively. Significant Grad 3/4 toxicities were identified in 46 (9.4%) patients with predominantly hematotoxicity and gastrointestinal toxicity.

Conclusions: We were able to reproduce the therapeutic response rate of clinical studies with a selected pool of patients. We verified the efficacy of docetaxel in general in patients with CRPC. A flare-up phenomenon within the first three cycles was observed in 30% of patients, which suggest to continue therapy for at least that period of time.
Phase III Randomized Study of 4 Weeks of High-Dose Interferon-α-2b in Stage T2bNO, T3a-bNO, T4a-bNO, and T1-4N1a-2a (microscopic) Melanoma: A Trial of the Eastern Cooperative Oncology Group–American College of Radiology Imaging Network Cancer Research Group (E1697)
Authors: Agarwala Sanjiv S. , Lee Sandra J. , Yip Waiki , Rao Uma N. , Tarhini Ahmad A. , Cohen Gary I. , Reintgen Douglas S. , Evans Terry L. , Brell Joanna M. , Albertini Mark R. , Atkins Michael B. , Dakhil Shaker R. , Conry Robert M. , Sosman Jeffrey A. , Flaherty Lawrence E. , Sondak Vernon K. , Carson William E. , Smylie Michael G. , Pappo Alberto S. , Kefford Richard F. , Kirkwood John M.
Published: February 2017

Purpose

To test the efficacy of 4 weeks of intravenous (IV) induction with high-dose interferon (IFN) as part of the Eastern Cooperative Oncology Group regimen compared with observation (OBS) in patients with surgically resected intermediate-risk melanoma.

Patients and Methods

In this intergroup international trial, eligible patients had surgically resected cutaneous melanoma in the following categories: (1) T2bN0, (2) T3a-bN0, (3) T4a-bN0, and (4) T1-4N1a-2a (microscopic). Patients were randomly assigned to receive IFN α-2b at 20 MU/m2/d IV for 5 days (Monday to Friday) every week for 4 weeks (IFN) or OBS. Stratification factors were pathologic lymph node status, lymph node staging procedure, Breslow depth, ulceration of the primary lesion, and disease stage. The primary end point was relapse-free survival. Secondary end points included overall survival, toxicity, and quality of life.

Results

A total of 1,150 patients were randomly assigned. At a median follow-up of 7 years, the 5-year relapse-free survival rate was 0.70 (95% CI, 0.66 to 0.74) for OBS and 0.70, (95% CI, 0.66 to 0.74) for IFN ( P = .964). The 5-year overall survival rate was 0.83 (95% CI, 0.79 to 0.86) for OBS and 0.83 (95% CI, 0.80 to 0.86) for IFN ( P = .558). Treatment-related grade 3 and higher toxicity was 4.6% versus 57.9% for OBS and IFN, respectively ( P < .001). Quality of life was worse for the treated group.

Conclusion

Four weeks of IV induction as part of the Eastern Cooperative Oncology Group high-dose IFN regimen is not better than OBS alone for patients with intermediate-risk melanoma as defined in this trial.
Pain Management and Use of Opioids in Pediatric Oncology in India: A Qualitative Approach
Authors: Angelini Paola , Boydell Katherine M. , Breakey Vicky , Kurkure Purna A. , Muckaden Marian A. , Bouffet Eric , Arora Brijesh
Published: February 2017

Purpose

Consumption of medical opium for pain relief in India is low, despite the country being one of the main world producers of the substance. We investigated obstacles to opioid use and physician perceptions about optimal pain management in pediatric oncology patients in India.

Methods

Semistructured interviews were conducted with oncologists who work in pediatric oncology settings. A mixed sampling strategy was used, including maximum variation and confirmation and disconfirmation of cases, as well as snowball sampling. Key informants were identified. Interviews were audio recorded, transcribed verbatim, and analyzed by thematic analysis methodology.

Results

Twenty-three interviews were performed across 20 Indian institutions. The main obstacles identified were lack of financial resources, inadequate education of health care providers on pain management, insufficient human resources (particularly lack of dedicated trained oncology nurses), poor access to opioids, and cultural perceptions about pain. Children from rural areas, treated in public hospitals, and from lower socioeconomic classes appear disadvantaged. A significant equality gap exists between public institutions and private institutions, which provide state-of-the-art treatment.

Conclusion

The study illuminates the complexity of pain management in pediatric oncology in India, where financial constraints, lack of education, and poor access to opioids play a dominant role, but lack of awareness and cultural perceptions about pain management among health care providers and parents emerged as important contributing factors. Urgent interventions are needed to optimize care in this vulnerable population.
Hematopoietic Stem-Cell Transplantation in the Resource-Limited Setting: Establishing the First Bone Marrow Transplantation Unit in Bangladesh
Authors: Yeh Albert C. , Khan Mohiuddin A. , Harlow Jason , Biswas Akhil R. , Akter Mafruha , Ferdous Jannatul , Ara Tasneem , Islam Manirul , Caron Martin , Barron Anne-Marie , Moran Jenna , Brezina Mark , Nazneen Humayra , Kamruzzaman Md , Saha Anup , Marshall Ariela , Afrose Salma , Stowell Christopher , Preffer Frederic , Bangsberg David , Goodman Annekathryn , Attar Eyal , McAfee Steven , Spitzer Thomas R. , Dey Bimalangshu R.
Published: February 2017

Purpose

Treatment of malignant and nonmalignant hematologic diseases with hematopoietic stem-cell transplantation (HSCT) was first described almost 60 years ago, and its use has expanded significantly over the last 20 years. Whereas HSCT has become the standard of care for many patients in developed countries, the significant economic investment, infrastructure, and health care provider training that are required to provide such a service have prohibited it from being widely adopted, particularly in developing countries.

Methods

Over the past two decades, however, efforts to bring HSCT to the developing world have increased, and several institutions have described their efforts to establish such a program. We aim to provide an overview of the current challenges and applications of HSCT in developing countries as well as to describe our experience in developing an HSCT program at Dhaka Medical College and Hospital in Bangladesh via a partnership with health care providers at Massachusetts General Hospital.

Results and Conclusion

We discuss key steps of the program, including the formation of a collaborative partnership, infrastructure development, human resource capacity building, and financial considerations.
Breast Cancer and HIV in Sub-Saharan Africa: A Complex Relationship
Authors: Grover Surbhi , Martei Yehoda M. , Puri Priya , Prabhakar Pooja , Mutebi Miriam , Balogun Onyinye D. , Price Aryeh J. , Freeman Alexandra H. , Narasimhamurthy Mohan , Rodin Danielle , Rayne Sarah , Zetola Nicola M.
Published: February 2017

Introduction

The number and lifespan of individuals living with HIV have increased significantly with the scale-up of antiretroviral therapy. Furthermore, the incidence of breast cancer in women with HIV is growing, especially in sub-Saharan Africa (SSA). However, the association between HIV infection and breast cancer is not well understood.

Methods

A literature search was performed to identify articles published in journals pertaining to breast cancer and HIV, with an emphasis on SSA. Selected US-based studies were also identified for comparison.

Results

Among the 56 studies reviewed, the largest study examined 314 patients with breast cancer and HIV in the United States. There is no consensus on whether HIV infection acts as a pro-oncogenic or antioncogenic factor in breast cancer, and it may have no relation to breast cancer. A higher incidence of breast cancer is reported in high-income countries than in SSA, although breast cancer in SSA presents at a younger age and at a more advanced stage. Some studies show that patients with breast cancer and HIV experience worse chemotherapy toxicity than do patients without HIV. Data on treatment outcomes are limited. The largest study showed worse treatment outcomes in patients with HIV, compared with their counterparts without HIV.

Conclusion

HIV infection has not been associated with different clinical presentation of breast cancer. However, some evidence suggests that concurrent diagnosis of HIV with breast cancer is associated with increased therapy-related toxicity and worse outcomes. Systematic prospective studies are needed to establish whether there is a specific association between breast cancer and HIV.
Developing a Breast Cancer Screening Program in Nigeria: Evaluating Current Practices, Perceptions, and Possible Barriers
Authors: Olasehinde Olalekan , Boutin-Foster Carla , Alatise Olusegun I. , Adisa Adewale O. , Lawal Oladejo O. , Akinkuolie Akinbolaji A. , Adesunkanmi Abdul-Rasheed K. , Arije Olujide O. , Kingham Thomas P.
Published: February 2017

Purpose

In low- and middle-income countries like Nigeria, women present with advanced breast cancer at an earlier age. Given the limited resources, development of screening programs that parallel resource capabilities of low- and middle-income countries is imperative. The objective of this study was to evaluate the perceptions, practices, and barriers regarding clinical breast examination (CBE) screening in a low-income community in Nigeria.

Materials and Methods

A cross-sectional survey of women age 40 years or older in Ife, Nigeria, using multistaged sampling was performed. Information on sociodemographics, knowledge of breast cancer, screening practices, and willingness to participate in CBE screening was obtained using an interviewer-administered questionnaire.

Results

A total of 1,169 women whose ages ranged from 40 to 86 years (mean age, 47.7 years; standard deviation, 8.79 years) were interviewed. The majority of women (94%) knew about breast cancer, whereas 27.5% knew someone who had had breast cancer, the majority of whom (64.5%) had died of the disease. Of the 36% of women who had breast screening recommended to them, only 19.7% had an actual CBE. Of these, only 6% had it in the last year. The majority of women (65.4%) were willing to have regular CBEs and did not care about the sex of the examiner in most instances. Lack of perceived need was the reason cited by women unwilling to participate.

Conclusion

The majority of women were aware of breast cancer and knew it as a fatal disease. With the relatively encouraging number of those willing to be examined, a carefully designed CBE program coupled with advocacy to correct uneducated beliefs seems promising.
Financial Burden for Patients With Chronic Myeloid Leukemia Enrolled in Medicare Part D Taking Targeted Oral Anticancer Medications
Authors: Shen Chan , Zhao Bo , Liu Lei , Shih Ya-Chen Tina
Published: February 2017

Purpose:

The number of targeted oral anticancer medications (TOAMs) has grown rapidly in the past decade. The high cost of TOAMs raises concerns about the financial aspect of treatment, especially for patients enrolled in Medicare Part D plans because of the coverage gap.

Methods:

We identified patients with chronic myeloid leukemia (CML) who were new TOAM users from the SEER registry data linked with Medicare Part D data, from years 2007 to 2012. We followed these patients throughout the calendar year when they started taking the TOAMs and examined their out-of-pocket (OOP) payments and gross drug costs, taking into account their benefit phase, plan type, and cost share group.

Results:

We found that 726 (81%) of the 898 patients with CML who received TOAMs had reached the catastrophic phase of their Medicare Part D benefit within the year of medication initiation, with a large majority of patients reaching this phase in less than a month. Patients without subsidies showed a clear pattern of a spike in OOP payments when they began treatment with TOAMs. The OOP payment for patients with subsidies was substantially lower. The monthly gross drug costs were similar between patients with and without subsidies.

Conclusion:

Patients experience quick entry and exit from the coverage gap (also called the donut hole) as a result of the high price of TOAMs. Closing the donut hole will provide financial relief during the initial month(s) of treatment but will not completely eliminate the financial burden.
Institutional Trading and Hedge Fund Activism
Authors: Gantchev Nickolay , Jotikasthira Chotibhak
Published: February 2017

This paper investigates the role of institutional trading in the emergence of hedge fund activism—an important corporate governance mechanism. We demonstrate that institutional sales raise a firm’s probability of becoming an activist target. Furthermore, by exploiting the funding circumstances of individual institutions, we establish that such effects occur through a liquidity channel, i.e., the activist camouflages his purchases among other institutions’ liquidity sales. Additional evidence supports our conclusion. First, activist purchases closely track institutional sales at the daily frequency. Second, such synchronicity is stronger among targets with lower expected monitoring benefits, suggesting that gains from trading with other institutions supplement these benefits in the activist’s targeting decision. Finally, we find that institutional sales accelerate the timing of a campaign at firms already followed by activists rather than attract attention to unlikely targets. Taken together, our findings offer a novel empirical perspective on the liquidity theories of activism; while activists screen firms on the basis of fundamentals, they pick specific targets at a particular time by exploiting institutional liquidity shocks.

The Internet appendix is available at https://doi.org/10.1287/mnsc.2016.2654 .

This paper was accepted by Amit Seru, finance.
The research nursing team: providing evidence, promoting high-quality care
Authors: Stone Ruth
Published: February 2017

Ruth Stone, a final-year student at the University of East Anglia, discusses her first introduction to research nurses, and how this placement week will influence her approach to research in future
Ensuring cancer nursing is up to date
Authors: Henry Richard
Published: February 2017

Richard Henry, Lecturer in Cancer Nursing, School of Nursing and Midwifery, Queen's University Belfast and President, UK Oncology Nursing Society
Adsorptive removal of catechol and resorcinol by orange flavedo (citrus sinensis): mechanisms based on the flavedo com-ponents d-limonene, carotenoids, ascorbates, flavonoids and hydroxycinnamic acids
Authors: Theophile Kamgaing , Giscard Doungmo , Jimmy Julio Ngouoko Kouonang , Francis Merlin Tchieno Melataguia , Joseph Ketcha MBadkam
Published: February 2017

Orange flavedo and its adsorption behavior towards catechol (Ctc) and resorcinol (Res) were studied. Adsorption experiments were conducted in batch mode at room temperature. X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDX), Brunauerâˆ’Emmettâˆ’Teller (BET) and Fourier transform infrared (FTIR) data were used to characterize the biosorbent. The Effects of various parameters including equilibrium pH, sorbent dosage, initial adsorbate concentration and contact time were investigated. The optimum contact time and pH for the removal of Ctc and Res were 35 min and pH 2 respectively. The adsorption isotherms fitted well with Freundlich model, the adsorption of Ctc and Res being multilayer and the surface of orange flavedo heterogeneous; the pseudo-second order kinetic model better reflects the adsorption phenomena. An adsorption mechanism based on the molecules grafted to the surface of the orange flavedo is proposed in this study. 0.2 gram of the biosorbent was sufficient to completely eliminate 2.2 milligrams of resorcinol and catechol from solution. Therefore, non-modified orange flavedo is a promising candidate, as a low-cost biosorbent, for the removal of Ctc and Res from aqueous solution.
Przyszłość nauki, przyszłość uniwersytetu. Fantastycznonaukowe prognozy zaniku wiedzy naukowej
Authors: Brzostek Dariusz
Published: February 2017

The predictions of science fiction play an important part in the cultural landscape of contemporary western culture, being integral to the popular culture (novels, movies, TV series, graphic novels). Science fiction narratives predict the future of society, technology, culture but also – the science itself and a university as a scientific institution. The aim of this work is to shed light on the depiction of the future of science, knowledge, and university in the science fiction works, predicting the ineluctable societal collapse. The essay focuses on the use of the scientific discourse and scientific knowledge in the chosen science fiction narratives by Stanisław Lem, Walter M. Miller jr., John Brunner, and Paolo Bacigalupi.
Filmowe dybuki: od żydowskiej legendy do polskiego koszmaru sennego
Authors: Nowakowski Jacek
Published: February 2017

The article discusses several screen adaptations of the drama Dybbuk or Between Two Worlds  by Szymon An-ski. Written on the basis of an old Jewish legend, An-ski’s play has provided inspiration for many movies. The four analysed works represent different cultural traditions and film genres and come from different decades of the cinema history. Diverse as they are, these four works emphasize different issues. They are: Dybbuk by M. Waszyński – the best Polish movie in Yiddish exploring the Jewish folklore; A Serious Man  by the Coen brothers, with a ‘dybbuk’ prologue that redefines their art towards the Judaic tradition, as well as two other works that are strongly characteristic of the film genres that they represent: The Possession  by O. Bornedal, using the poetics of religious horror, and the Polish thriller The Demon  by M. Wrona, drawing from the tradition of the national drama as defined by Wesele  [The Wedding ] by S. Wyspiański and its screen adaptations and travestations.
Fotografie nieistniejącego świata. O polskiej sztuce fantastycznej
Authors: Grodecka Aneta
Published: February 2017

Starting with a reconstruction of the views of philosophers and aesthetes on the topic of fantastic images, the Author aims to characterize fantasy art. She describes the reception of this art in Poland, characterizes its determinants, and defines the trend, indicating the most important examples of artistic works. While exploring this approach, she refers to Waldemar Okoń, Jerzy Malinowski, Tomasz Gryglewicz, and Antoni Smuszkiewicz. The convention of fantasy art appears to be a vital, developmental quality, an expression of the rebellion of consciousness against simplifications.
Monetary policy in a low inflation environment and expectations of market participants
Authors: Szyszko Magdalena
Published: February 2017

The paper focuses on inflation expectations management in a low inflation or deflation environment. Firstly, it presents theoretical findings on avoiding and escaping the deflation trap. They are closely related to expectations management as expectations become the main transmission channel in the zero lower bound (ZLB) environment. In response to the recent economic crisis some of the following solutions have been applied by central banks: quantitative easing, forward guidance and depreciation.  Their use is not detrimental to the framework of inflation targeting strategy. Secondly, some remarks about the difficulties of measuring expectations during the occurrence of ZLB and in a crisis situation are made. The information on expectations levels, their distribution, volatility and the degree to which they are anchored is crucial for central banks, especiallywhen the expectations offer the most effective way to affect the economy. Finally, a comparison of the expectations quantified with the Carlson and Parkin probabilistic method and its version adjusted for non-positive scaling factor periods is made. The empirical part of the research covers Poland (July 2014 – December 2015) and Sweden (November 2012 – December 2015). Both countries experience deflation, and (additionally) Sweden operates under ZLB. An alternative method of quantification smoothes the expectations and reduces their volatility. The subject dealt with in this paper is still under theoretical and empirical examination. No conclusion as to the optimal solution for expectations management is made.
Individual differences in second language speech perception across tasks and contrasts: The case of English vowel contrasts by Korean learners
Authors: Kim Donghyun , Clayards Meghan , Goad Heather
Published: February 2017

The present study examines whether individual differences in second language (L2) learners’ perceptual cue weighting strategies reflect systematic abilities. We tested whether cue weights indicate proficiency in perception using a naturalistic discrimination task as well as whether cue weights are related across contrasts for individual learners. Twenty-four native Korean learners of English completed a two-alternative forced choice identification task on /ɪ/-/i/ and /ɛ/-/æ/ contrasts varying orthogonally in formant frequency and duration to determine their perceptual cue weights. They also completed a two-talker AX discrimination task on natural productions of the same vowels. In the cue-weighting task, we found that individual L2 learners varied greatly in the extent to which they relied on particular phonetic cues. However, individual learners’ perceptual weighting strategies were consistent across contrasts. We also found that more native-like performance on this task – reliance on spectral differences over duration – was related to better recognition of naturally produced vowels in the discrimination task. Therefore, the present study confirms earlier reports that learners vary in the extent to which they rely on particular phonetic cues. Additionally, our results demonstrate that these individual differences reflect systematic cue use across contrasts as well as the ability to discriminate naturally produced stimuli.
In-Cylinder Heat Transfer Modelling
Authors: Žák Zdeněk , Emrich Miloslav , Takáts Michal , Macek Jan
Published: February 2017

The goal of the paper is to discuss specific features of the in-cylinder heat transfer calculation based on widely used empirical formulas. The potential of in-house codes compared with commercially available software packages is presented. The principles of user models in the GT-SUITE environment are also explained. The results of calibrated models are briefly discussed.
Emergent Magnéli-type crystal phases and their mixture in pressurized sulfur hydride
Authors: Akashi Ryosuke , Sano Wataru , Arita Ryotaro , Tsuneyuki Shinji
Published: February 2017

The pressure-induced superconductivity in sulfur hydride has recently received tremendous amount of interest for its record-breaking transition temperature (T