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1.  Innovations that reach the patient: early health technology assessment and improving the chances of coverage and implementation 
ecancermedicalscience  2016;10:683.
With growing concerns for the sustainability of the financial burden that health care—and especially cancer services—poses on the national budgets, the role of health economic analyses in coverage decisions is likely to grow. One of the strategies for the biomedical research field—also in oncology research—to foster coverage and health system implementation, is to anticipate this new role and to involve health technology assessment techniques earlier in various stages of translational research.
In this article, we elaborate on the early involvement of health technology assessment in translational research and the concept of Coverage with Evidence Development in The Netherlands Cancer Institute and give two case examples that are currently ongoing: (1) tumour infiltrating lymphocytes therapy for metastatic melanoma; and (2) high-dose chemotherapy for BRCA1-like subgroup in triple-negative breast cancer.
We conclude with recommendations for institutional policy.
doi:10.3332/ecancer.2016.683
PMCID: PMC5102688  PMID: 27899956
coverage with evidence development; health technology assessment; tumour infiltrating lymphocytes; high-dose chemotherapy
2.  Next-generation sequencing in NSCLC and melanoma patients: a cost and budget impact analysis 
ecancermedicalscience  2016;10:684.
Next-generation sequencing (NGS) has reached the molecular diagnostic laboratories. Although the NGS technology aims to improve the effectiveness of therapies by selecting the most promising therapy, concerns are that NGS testing is expensive and that the ‘benefits’ are not yet in relation to these costs. In this study, we give an estimation of the costs and an institutional and national budget impact of various types of NGS tests in non-small-cell lung cancer (NSCLC) and melanoma patients within The Netherlands. First, an activity-based costing (ABC) analysis has been conducted on the costs of two examples of NGS panels (small- and medium-targeted gene panel (TGP)) based on data of The Netherlands Cancer Institute (NKI). Second, we performed a budget impact analysis (BIA) to estimate the current (2015) and future (2020) budget impact of NGS on molecular diagnostics for NSCLC and melanoma patients in The Netherlands. Literature, expert opinions, and a data set of patients within the NKI (n = 172) have been included in the BIA. Based on our analysis, we expect that the NGS test cost concerns will be limited. In the current situation, NGS can indeed result in higher diagnostic test costs, which is mainly related to required additional tests besides the small TGP. However, in the future, we expect that the use of whole-genome sequencing (WGS) will increase, for which it is expected that additional tests can be (partly) avoided. Although the current clinical benefits are expected to be limited, the research potentials of NGS are already an important advantage.
doi:10.3332/ecancer.2016.684
PMCID: PMC5102690  PMID: 27899957
Next-generation sequencing; test costs; budget impact; melanoma; NSCLC; personalised medicine; targeted therapy
3.  Comparison between standard and reduced volume radiotherapy in bladder preservation trimodality protocol for muscle-invasive bladder cancer patients 
ecancermedicalscience  2016;10:682.
Aim
Our aim is to compare the toxicity, pelvic nodal relapse, and overall survival of whole bladder irradiation only to the standard technique of whole pelvis irradiation followed by bladder boost in patients with muscle-invasive bladder carcinoma undergoing bladder preservation protocol.
Material and method
A total of 60 patients with transitional cell carcinoma, stage T2-3, N0, M0 bladder cancer were subjected to maximal transurethral resection bladder tumour (TURB). Then, the patients were randomised into two groups: group I (30 patients) to receive whole pelvis radiotherapy 44 Gy followed by 20 Gy bladder boost. While group II (30 patients) were randomised to receive whole bladder radiotherapy alone for a total dose of 64 Gy. In both groups, concomitant cisplatin and paclitaxel were given weekly throughout the whole course of radiotherapy where conventional 2 Gy/fraction were used. Additionally, four cycles of adjuvant cisplatin and paclitaxel were given after the end of the chemoradiotherapy induction course.
Results
The first assessment after the induction chemoradiotherapy showed that complete response was achieved in 73.3% of patients in group I and 76.7% of the patients in group II. After a median follow-up of 2 years, regional relapse occurred in 7.1% of patients in group I and 10.3% in group II. (p = 1). Distant metastases were detected in 17.9% of patient in group I and 13.8% in group II (p = 0.73). The 2-year disease-free survival was 60% in group I and 63.3% in group II (p = 0.79). The whole 2-year overall survival was 75% in group I and 79.3% in group II (p = 0.689). Radiation gastrointestinal (GI) acute toxicity was higher in group I than in group II (p = 0.001), while late GI radiation toxicity was comparable in both groups.
Conclusion
Treating the bladder only, without elective pelvic nodal irradiation, did not compromise pelvic control rate, but significantly decreased the acute radiation toxicity.
doi:10.3332/ecancer.2016.682
PMCID: PMC5102689  PMID: 27899955
bladder cancer; lymph nodes; radiotherapy; trimodality protocol
4.  Phosphoethanolamine and the danger of unproven drugs 
ecancermedicalscience  2016;10:681.
The use of unproven forms of therapy in cancer treatment is very common. In Brazil, the distribution by researchers to patients of an investigational agent called phophoethanolamine (PHOS) has led to a widely publicized scientific scandal. PHOS is a precursor to components of the cell membrane, with some published pre-clinical studies suggesting cytotoxic activity in cancer cells. The willingness of courts and of legislators to guarantee access to PHOS in spite of the lack of any clinical data and against the recommendations of scientific and medical organisations underscores the risks that unproven agents pose to regulatory authorities, health care systems and patients, and bears resemblance to other cases such as the controversy surrounding the approval of zidovudine for AIDS treatment by the FDA.
doi:10.3332/ecancer.2016.681
PMCID: PMC5102686  PMID: 27899954
phosphoethanolamine; cancer; science; Brazil; ethics
5.  Repurposing Drugs in Oncology (ReDO)—Propranolol as an anti-cancer agent 
ecancermedicalscience  2016;10:680.
Propranolol (PRO) is a well-known and widely used non-selective beta-adrenergic receptor antagonist (beta-blocker), with a range of actions which are of interest in an oncological context. PRO displays effects on cellular proliferation and invasion, on the immune system, on the angiogenic cascade, and on tumour cell sensitivity to existing treatments. Both pre-clinical and clinical evidence of these effects, in multiple cancer types, is assessed and summarised and relevant mechanisms of action outlined. In particular there is evidence that PRO is effective at multiple points in the metastatic cascade, particularly in the context of the post-surgical wound response. Based on this evidence the case is made for further clinical investigation of the anticancer effects of PRO, particularly in combination with other agents. A number of trials are on-going, in different treatment settings for various cancers.
doi:10.3332/ecancer.2016.680
PMCID: PMC5102691  PMID: 27899953
Propranolol; beta-blockers; drug repurposing; ReDO project
6.  Prognostic and predictive implications of Sokal, Euro and EUTOS scores in chronic myeloid leukaemia in the imatinib era—experience from a tertiary oncology centre in Southern India 
ecancermedicalscience  2016;10:679.
Chronic myeloid leukaemia (CML) is a myeloproliferative disorder. Over the years many prognostic models have been developed to better risk stratify this disease at baseline. Sokal, Euro, and EUTOS scores were developed in varied populations initially receiving various therapies. Here we try to identify their predictive and prognostic implication in a larger population of Indian patients with CML-CP (chronic phase) in the imatinib era.
doi:10.3332/ecancer.2016.679
PMCID: PMC5102687  PMID: 27899952
CML; Sokal score; Euro score; EUTOS score
7.  The first case of benign multicystic mesothelioma presenting as a splenic mass 
ecancermedicalscience  2016;10:678.
Multicystic mesothelioma (MM) is a relatively rare tumour arising in the pelvic peritoneum of the tuboovarian region of young woman. Exceptionally, MM occurs on the serosal surfaces of various organs including kidney, bladder, lymph nodes, and liver. We report here the first case of MM wherein a 58-year-old woman with a previous history of endometriosis of the right ovary presented with a large multicystic mass of the spleen. The diagnosis of MM was made on a surgical specimen after splenectomy. A histopathologic examination is always necessary for the diagnosis of MM which should be differentiated from other lesions particularly from cystic lymphangioma. At one year follow-up, the patient had no evidence of recurrence. Despite the high frequency of local recurrences, MM is a benign lesion and ‘en bloc’ surgical excision with prolonged follow-ups is the treatment of choice.
doi:10.3332/ecancer.2016.678
PMCID: PMC5102685  PMID: 27899951
multicystic mesothelioma; spleen; peritoneum; immunohistochemistry; prognosis
8.  Conditional survival of metastatic renal cell carcinoma patients treated with high-dose interleukin-2 
ecancermedicalscience  2016;10:676.
Conditional survival (CS) is a clinically useful prediction measure which adjusts a patient’s prognosis based on their duration of survival since initiation of therapy. CS has been described in numerous malignancies, and recently described in patients with metastatic renal cell carcinoma (mRCC) who received vascular endothelial growth factor tyrosine kinase inhibitor (VEGFTKI) therapy. However, CS has been not reported in the context of mRCC treated with high-dose interleukin-2 therapy (HDIL-2). A total of 176 patients with histologically confirmed metastatic clear cell RCC (mccRCC) treated with HDIL-2 at the University of Utah Huntsman Cancer Institute from 1988–2012 were evaluated. Using the Heng/IMDC model, they were stratified by performance status and prognostic risk groups. Two-year CS was defined as the probability of surviving an additional two years from initiation of HDIL-2 to 18 months after the start of HDIL-2 at three-month intervals. The median overall survival (OS) was 19.9 months. Stratifying patients into favourable (n = 35; 20%), intermediate (n = 110; 63%), and poor (n = 31; 18%) prognostic groups resulted in median OS of 47.5 (HR 0.57, 95% CI 0.35–0.88, p = 0.0106 versus intermediate), 19.6 (HR 0.33, 95% CI 0.10–0.33, p < 0.0001 versus poor), and 8.8 (HR 5.34, 95% CI 3.00–9.62, p < 0.0001 versus favourable) months respectively. Two-year overall CS increased from 43% at therapy initiation to 100% at 18 months. These results have significant ramifications in prognostication. Furthermore, it is important when counseling patients with mccRCC who have completed treatment with HDIL-2 and are in active follow-up.
doi:10.3332/ecancer.2016.676
PMCID: PMC5045298  PMID: 27729941
metastatic renal cell cancer; high-dose interleukin-2; conditional survival
9.  VERO® radiotherapy for low burden cancer: 789 patients with 957 lesions 
ecancermedicalscience  2016;10:677.
Purpose
The aim of this retrospective study is to evaluate patient profile, feasibility, and acute toxicity of RadioTherapy (RT) delivered by VERO® in the first 20 months of clinical activity.
Methods
Inclusion criteria: 1) adult patients; 2) limited volume cancer (M0 or oligometastatic); 3) small extracranial lesions; 4) treatment between April 2012 and December 2013 and 5) written informed consent. Two techniques were employed: intensity modulated radiotherapy (IMRT) and stereotactic body radiotherapy (SBRT). Toxicity was evaluated using Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer (RTOG/EORTC) criteria.
Results
Between April 2012 and December 2013, 789 consecutive patients (957 lesions) were treated. In 84% of them one lesion was treated and in 16% more than one lesion were treated synchronously/metachronously; first radiotherapy course in 85%, re-irradiation in 13%, and boost in 2% of cases. The treated region included pelvis 46%, thorax 38%, upper abdomen 15%, and neck 1%. Radiotherapy schedules included <5 and >5 fractions in 75% and 25% respectively. All patients completed the planned treatment and an acceptable acute toxicity was observed.
Conclusions
RT delivered by VERO® was administrated predominantly to thoracic and pelvic lesions (lung and urologic tumours) using hypofractionation. It is a feasible approach for limited burden cancer offering short and well accepted treatment with favourable acute toxicity profile. Further investigation including dose escalation and other available VERO® functionalities such as real-time dynamic tumour tracking is warranted in order to fully evaluate this innovative radiotherapy system.
doi:10.3332/ecancer.2016.677
PMCID: PMC5045299  PMID: 27729942
hypofractionation; IMRT; low burden cancer; SBRT; VERO®-system
10.  The analytical validation of the Oncotype DX Recurrence Score assay 
ecancermedicalscience  2016;10:675.
In vitro diagnostic multivariate index assays are highly complex molecular assays that can provide clinically actionable information regarding the underlying tumour biology and facilitate personalised treatment. These assays are only useful in clinical practice if all of the following are established: analytical validation (i.e., how accurately/reliably the assay measures the molecular characteristics), clinical validation (i.e., how consistently/accurately the test detects/predicts the outcomes of interest), and clinical utility (i.e., how likely the test is to significantly improve patient outcomes). In considering the use of these assays, clinicians often focus primarily on the clinical validity/utility; however, the analytical validity of an assay (e.g., its accuracy, reproducibility, and standardisation) should also be evaluated and carefully considered. This review focuses on the rigorous analytical validation and performance of the Oncotype DX® Breast Cancer Assay, which is performed at the Central Clinical Reference Laboratory of Genomic Health, Inc. The assay process includes tumour tissue enrichment (if needed), RNA extraction, gene expression quantitation (using a gene panel consisting of 16 cancer genes plus 5 reference genes and quantitative real-time RT-PCR), and an automated computer algorithm to produce a Recurrence Score® result (scale: 0–100). This review presents evidence showing that the Recurrence Score result reported for each patient falls within a tight clinically relevant confidence interval. Specifically, the review discusses how the development of the assay was designed to optimise assay performance, presents data supporting its analytical validity, and describes the quality control and assurance programmes that ensure optimal test performance over time.
doi:10.3332/ecancer.2016.675
PMCID: PMC5045300  PMID: 27729940
analytical validation; breast cancer; Oncotype DX; prognostic factor; Recurrence Score
11.  Is blue dye still required during sentinel lymph node biopsy for breast cancer? 
ecancermedicalscience  2016;10:674.
Background
In early breast cancer, the optimal technique for sentinel lymph node biopsy (SLNB) is the combined technique (radioisotope and Patent Blue V) which achieves high identification rates. Despite this, many centres have decided to stop using blue dye due to blue-dye-related complications (tattoo, anaphylaxis). We evaluated the SLNB identification rate using the combined technique with and without Patent Blue V and the blue-dye-related complication rates.
Methods
Clinical and histological data were analysed on patients undergoing SLNB between March 2014 and April 2015. SLNB was performed following standard hospital protocols using the combined technique.
Results
A total of 208 patients underwent SLNB and 160 patients (342 nodes) with complete operation notes were available for final analysis. The identification rate with the combined technique was 98.8% (n = 158/160), with blue dye alone 92.5% (n = 148/160) and with radioisotope alone 97.5% (n = 156/160). A total of 76.9% (263/342) of nodes were radioactive and blue, 15.5% (53/342) only radioactive and 2.3% (8/342) only blue, 5.3% (18/342) were neither radioactive nor blue. No anaphylactic reactions were reported and blue skin staining was reported in six (3.8%) patients.
Conclusion
The combined technique should continue be the preferred technique for SLNB and should be standardised. Radioisotope alone (but not blue dye alone) has comparable sentinel node identification rates in experienced hands. National guidelines are required to optimise operative documentation.
doi:10.3332/ecancer.2016.674
PMCID: PMC5045297  PMID: 27729939
breast cancer; sentinel lymph node biopsy; radioisotope; patent blue
12.  Highlights from the 1st Latin American meeting on metronomic chemotherapy and drug repositioning in oncology, 27–28 May, 2016, Rosario, Argentina 
ecancermedicalscience  2016;10:672.
Following previous metronomic meetings in Marseille (2011), Milano (2014), and Mumbai (2016), the first Latin American metronomic meeting was held in the School of Medical Sciences, National University of Rosario, Rosario, Argentina on 27 and 28 of May, 2016. For the first time, clinicians and researchers with experience in the field of metronomics, coming from different countries in Latin America, had the opportunity of presenting and discussing their work. The talks were organised in three main sessions related to experience in the pre-clinical, and clinical (paediatric and adult) areas. The different presentations demonstrated that the fields of metronomic chemotherapy and repurposing drugs in oncology, known as metronomics, constitute a branch of cancer therapy in permanent evolution, which have strong groups working in Latin
America, both in the preclinical and the clinical settings including large, adequately designed randomised studies. It was shown that metronomics offers treatments, which, whether they are combined or not with the standard therapeutic approaches, are not only effective but also minimally toxic, with the consequent improvement of the patient’s quality of life, and inexpensive, a feature very important in low resource clinical settings. The potential use of metronomic chemotherapy was proposed as a cost/effective treatment in low-/middle-income countries, for adjuvant therapy in selected tumours. The fundamental role of the governmental agencies and non-governmental alliances, as the Metronomic Global Health Initiative, in supporting this research with public interest was underlined.
doi:10.3332/ecancer.2016.672
PMCID: PMC5014555  PMID: 27610198
cancer; metronomic chemotherapy; drug repositioning; pre-clinic; paediatric; adult
13.  Simple trachelectomy during pregnancy for cervical cancer 
ecancermedicalscience  2016;10:673.
Invasive cervical cancer is rare during a pregnancy, even though it is one of the most frequently diagnosed neoplasias during that time. It is noted that around 30% of women diagnosed with cervical cancer are of reproductive age. This means that up to 3% of cases of cervical cancer are found in pregnant women or those who are in the post-birth period. A cervicovaginal Pap smear is performed as part of the regular checkup for a pregnant woman during the first visit so that cervical cancer can easily be diagnosed early in these women, detecting it early in up to 70–80% of cases. We present here the case of a patient with initial diagnosis of cervical cancer made around 20th week of pregnancy. It was then treated by a simple trachelectomy and cerclage during week 24. The pregnant woman gave birth to a healthy baby at the end of her pregnancy. Definitive treatment was completed three months after giving birth with a total hysterectomy and laparoscopic bilateral salpingectomy while preserving both ovaries. After 17 months of monitoring the patient showed no signs of reoccurrence. In conclusion, during the early stage of cervical cancer conservative management may be a reasonable option to preserve the current pregnancy.
doi:10.3332/ecancer.2016.673
PMCID: PMC5014553  PMID: 27610199
cancer of the cervix; pregnancy; early stage; management
14.  Outcome of radical prostatectomy in primary circulating prostate cell negative prostate cancer 
ecancermedicalscience  2016;10:671.
Introduction
Around 90% of prostate cancers detected using the serum prostate specific antigen (PSA) as a screening test are considered to be localised. However, 20–30% of men treated by radical prostatectomy experience biochemical failure within two years of treatment. The presence of primary circulating prostate cells (CPCs) in the blood of these men implies a dissemination of the tumour and could indicate a greater risk of treatment failure.
Objective
To evaluate the use of the number of primary CPCs detected before surgery in the prediction of biochemical failure at ten years.
Hypothesis
The dissemination of cancer cells to distant sites will determine the patient’s prognosis. The absence of primary CPCs in men undergoing radical prostatectomy for prostate cancer may imply a less aggressive disease and therefore could be utilised as a prognostic factor to predict biochemical failure after surgery.
Methods and patients
A single-centre observational study of a cohort of 285 men who underwent radical prostatectomy as monotherapy for prostate cancer, in whom the number of CPCs prior to treatment was determined, and who were followed up for ten years to determine biochemical failure. A Cox proportional risks with polynomial fractions analysis was used to predict biochemical failure based on the number of primary CPCs detected. A decision curve analysis was performed for the model obtained.
Results
Kaplan–Meier curves for biochemical free survival at ten years was 47.34% (95% CI 38.71–55.48%). It is important to note that in CPC negative men, the ten years Kaplan–Meier biochemical-free survival was 90.35% (95% CI 75.0–96.27) whereas in men who were primary CPC positive, the biochemical free survival rate was 30.00% (95% CI 20.34–40.60%).
The Coxs´model to predict biochemical failure using transformed data with a power of minus one for the number of primary CPCs detected, showed a Harrell´s C concordance index of 0.74 and a decision analysis curve showing a net benefit of CPC detection over other risk factors to predict biochemical failure.
Conclusions
The number of primary CPCs detected before surgery permits a good prediction of subsequent biochemical failure in men undergoing radical prostatectomy as monotherapy for prostate cancer. Men negative for primary CPCs have a biochemical-free survival of over 90% at ten years and should be considered for curative surgery.
doi:10.3332/ecancer.2016.671
PMCID: PMC5014557  PMID: 27610197
personalised medicine; genomics; biomarkers; targeted therapy; sequencing
15.  Adoptive cell therapy and modulation of the tumour microenvironment: new insights from ASCO 2016 
ecancermedicalscience  2016;10:ed59.
Abstract
Immuno-oncology has changed the landscape of cancer treatment in recent years. Immune checkpoint inhibitors (ICI) have shown survival advantage with long term remissions in a variety of cancers. However, there is another approach to harnessing the power of the immune system in combating cancer: the adoptive cell therapy (ACT) strategy. Although ACT is restricted to small specialized centres and has yet to deliver as much success as ICI, some important results were presented at this year’s ASCO meeting. Important lessons have been learned from these studies, including the prospects and challenges ahead. In this editorial, we summarize the important studies on ACT presented at the ASCO 2016 meeting and discuss the way forward.
doi:10.3332/ecancer.2016.ed59
PMCID: PMC5014558  PMID: 27610200
immunotherapy; adoptive cell therapy; immuno-oncology; chimeric antigen receptor-modified T cells; tumour infiltrating lymphocytes
16.  Maps and atlases of cancer mortality: a review of a useful tool to trigger new questions 
ecancermedicalscience  2016;10:670.
In this review we illustrate our view on the epidemiological relevance of geographically mapping cancer mortality.
In the first part of this work, after delineating the history of cancer mapping with a view on interpretation of Cancer Mortality Atlases, we briefly illustrate the ‘art’ of cancer mapping. Later we summarise in a non-mathematical way basic methods of spatial statistics.
In the second part of this paper, we employ the ‘Atlas of Cancer Mortality in the European Union and the European Economic Area 1993–1997’ in order to illustrate spatial aspects of cancer mortality in Europe. In particular, we focus on the cancer related to tobacco and alcohol epidemics and on breast cancer which is of particular interest in cancer mapping.
Here we suggest and reiterate two key concepts. The first is that a cancer atlas is not only a visual tool, but it also contain appropriate spatial statistical analyses that quantify the qualitative visual impressions to the readers even though at times revealing fallacy. The second is that a cancer atlas is by no means a book where answers to questions can be found. On the contrary, it ought to be considered as a tool to trigger new questions.
doi:10.3332/ecancer.2016.670
PMCID: PMC5014559  PMID: 27610196
cancer; atlas; epidemiology; geography; spatial statistics; tobacco-related cancers; alcohol-related cancers; breast cancer;  geographic medicine
17.  Highlights from the 2016 WIN Symposium, 27–29 June 2016, Paris: personalised therapy beyond next-generation sequencing 
ecancermedicalscience  2016;10:669.
The Worldwide Innovative Networking (WIN) consortium is an alliance of academic institutions, pharmaceutical partners, representatives from technology companies and charitable/health payer organisations from across the globe. For the last six years, the consortium’s aims have been to foster communication and collaboration between members, encourage dialogue in an open forum, and deliver clinical trial results that improve the care and outcomes of patients with cancer using the latest advances in genomic-based medicine.
The annual WIN Symposium, held over two days, is a chance for its members to come together and discuss ongoing research, recent announcements, and introduce new developments in personalised medicine. This year’s conference, held in Paris, France 27–29 June, consisted of six dedicated sessions, including two debates, and posters from members and participating organisations, all focusing on the latest therapeutic advances and updates in genomic analysis.
Special highlights from this year included discussion of the MINDACT clinical trial, which uses a gene expression test to identify patients with breast cancer who can safely forego adjuvant chemotherapy, and the reflections on the SHIVA trial. Of particular interest to many speakers was the utilisation of liquid biopsy samples to produce near real time snapshots of tumour mutational profiles and vulnerability.
doi:10.3332/ecancer.2016.669
PMCID: PMC5014556  PMID: 27610195
personalised medicine; genomics; biomarkers; targeted therapy; sequencing
18.  Small cell neuroendocrine tumour of the endometrium and the importance of pathologic diagnosis 
ecancermedicalscience  2016;10:668.
Small cell carcinoma of the endometrium is a very rare entity. They are very aggressive tumours, with a poor prognosis. They represent a clinical challenge because of a lack of a standardised treatment. We see here a case of a 67-year-old woman with a history of a lobular breast carcinoma, diagnosed in 2002. After presenting with postmenopausal vaginal bleeding in October 2014, she underwent a hysteroscopy-guided biopsy which revealed a metastasis of breast carcinoma. A hysterectomy and bilateral oophorectomy was performed because of uncontrolled uterine bleeding. The pathologic diagnosis was small cell carcinoma (SCC) of the endometrium. A surgical complete cytoreduction was achieved after the case being presented in a multidisciplinary tumour board. Pathologic results revealed metastasis from peritoneal implants of SCC on the endometrium, and metastasis in pelvic and para-aortic lymph nodes from serous carcinoma of the endometrium. A total of four cycles of adjuvant chemotherapy based on cisplatin (80mg/m² day one) and etoposide (100mg/m² day one, two, three) every 21 days was given. The patient experienced persistent disease and died 17 months after the diagnosis. SCC of the endometrium is a very rare and aggressive disease that requires an individualised multidisciplinary management.
doi:10.3332/ecancer.2016.668
PMCID: PMC5014552  PMID: 27610194
small neuroendocrine tumour; endometrium; pathology diagnosis; endometrial cancer
19.  Children’s palliative care now! Highlights from the second ICPCN conference on children’s palliative care, 18–21 May 2016, Buenos Aires, Argentina 
ecancermedicalscience  2016;10:667.
The International Children’s Palliative Care Network held its second international conference on children’s palliative care in Buenos Aires, Argentina, from the 18th–21st May 2016. The theme of the conference was ‘Children’s Palliative Care…. Now!’ emphasising the need for palliative care for children now, as the future will be too late for many of them. Six pre-conference workshops were held, addressing issues connected to pain assessment and management, adolescent palliative care, ethics and decision-making, developing programmes, the basics of children’s palliative care, and hidden aspects of children’s palliative care. The conference brought together 410 participants from 40 countries. Plenary, concurrent, and poster presentations covered issues around the status of children’s palliative care, genetics, perinatal and neonatal palliative care, the impact of children’s palliative care and the experiences of parents and volunteers, palliative care as a human right, education in children’s palliative care, managing complex pain in children, spiritual care and when to initiate palliative care. The ‘Big Debate’ explored issues around decision-making and end of life care in children, and gave participants the opportunity to explore a sensitive and thought provoking topic. At the end of the conference, delegates were urged to sign the Commitment of Buenos Aires which called for governments to implement the WHA resolution and ensure access to palliative care for neonates, children and their families, and also commits us as palliative care providers to share all that we can and collaborate with each other to achieve the global vision of palliative care for all children who need it. The conference highlighted the ongoing issues in children’s palliative care and participants were continually challenged to ensure that children can access palliative care NOW.
doi:10.3332/ecancer.2016.667
PMCID: PMC5014554  PMID: 27610193
palliative care; children; international; commitment; integration; education; research; Argentina; WHA resolution
20.  Negative trials in ovarian cancer: is there such a thing as too much optimism? 
ecancermedicalscience  2016;10:ed58.
Recently, two clinical trials of novel agents in metastatic ovarian cancer were published: a phase 3 study of nintedanib and a phase 2 study of volasertib. There seemed to be discordance between the results and conclusions in the publication of both these trials. Despite not very optimistic results, the studies concluded optimistically in favor of the new agents under study. Using these examples, we point out the discrepancies and the risks of concluding optimistically based on statistical significance when the actual benefit is minimal. We also appeal against conducting large phase 3 trials that require significant resources without good phase 2 evidence for doing so.
doi:10.3332/ecancer.2016.ed58
PMCID: PMC4990052  PMID: 27594913
ovarian cancer; statistical significance; clinical trials; angiogenesis inhibitor; nintedanib; volasertib
21.  The role of surgery in advanced epithelial ovarian cancer 
ecancermedicalscience  2016;10:666.
Nowadays, the standard management of advanced epithelial ovarian cancer is correct surgical staging and optimal tumour cytoreduction followed by platinum and taxane-based chemotherapy. Standard surgical staging consists of peritoneal washings, total hysterectomy, and bilateral salpingo-oophorectomy, inspection of all abdominal organs and the peritoneal surface, biopsies of suspicious areas or randomised biopsies if they are not present, omentectomy and para-aortic lymphadenectomy. After this complete surgical staging, the International Federation of Gynaecology and Obstetrics (FIGO) staging system for ovarian cancer is applied to determine the management and prognosis of the patient. Complete tumour cytoreduction has shown an improvement in survival. There are some criteria to predict cytoreduction outcomes based on serum biomarkers levels, preoperative imaging techniques, and laparoscopic-based scores. Optimised patient selection for primary cytoreduction would determine patients who could benefit from an optimal cytoreduction and might benefit from interval surgery. The administration of intraperitoneal chemotherapy after debulking surgery has shown an increase in progression-free survival and overall survival, especially in patients with no residual disease after surgery. It is considered that 3–17% of all epithelial ovarian carcinoma (EOC) occur in young women that have not fulfilled their reproductive desires. In these patients, fertility-sparing surgery is a worthy option in early ovarian cancer.
doi:10.3332/ecancer.2016.666
PMCID: PMC4990056  PMID: 27594911
ovarian cancer; treatment; surgical treatment; cytoreduction; intraperitoneal chemotherapy
22.  Oral manifestations of lymphoma: a systematic review 
ecancermedicalscience  2016;10:665.
Lymphoma is a malignant disease with two forms: Hodgkin’s lymphoma (HL) and non-Hodgkin’s lymphoma (NHL). Non-Hodgkin’s lymphoma is diagnosed in extranodal sites in 40% of cases, and the head and neck region is the second most affected, with an incidence of 11–33%, while HL has a very low incidence in extranodal sites (1–4%). The aim of this study was to identify the oral manifestations of lymphoma through a systematic literature review, which we conducted using the PubMed, Lilacs, Embase, and Cochrane Library databases. We found 1456 articles, from which we selected 73. Among the intraoral findings, the most frequent were ulcerations, pain, swelling, and tooth mobility, while the extraoral findings included facial asymmetry and cervical, submandibular, and submental lymphadenopathy. Among the few studies reporting imaging findings, the most cited lesions included hypodense lesions with diffuse boundaries, bone resorptions, and tooth displacements. The publications reviewed highlight gaps in the areas of early detection, diagnosis, and proper treatment.
doi:10.3332/ecancer.2016.665
PMCID: PMC4990057  PMID: 27594910
lymphoma; oral cavity; dental care; oral manifestations
23.  An extremely rare case of a high-grade pleomorphic cardiac sarcoma and likely cerebral metastasis in a young patient 
ecancermedicalscience  2016;10:664.
To date, there have been less than a 100 confirmed case reports of primary cardiac malignant fibrous histiocytomas, a rare form of sarcoma. In this report, we discuss the case of a 15-year-old girl who initially presented with a histiocytic cerebral sarcoma that was treated with aggressive resection and chemotherapy. Three years later, the same patient developed increasing shortness of breath and was found to have a high-grade pleomorphic undifferentiated cardiac sarcoma that likely represents the primary tumour from which the cerebral lesion metastasised. This represents an extremely unique case; in 2010, a research group in Germany claimed the very first description of a true cardiac sarcoma with brain metastasis [1]. However, even as far back as 1960, there were three case reports [2] and more extensive sarcoma studies recently have revealed further cases [3]. Nevertheless, there have probably been less than 10 cases in the literature up until this point.
doi:10.3332/ecancer.2016.664
PMCID: PMC4990053  PMID: 27594909
sarcoma; cardiac tumours; cardiac MRI; leiomyosarcoma
24.  Time-dependent image changes after ethanol injection into the pancreas: an experimental study using a porcine model 
ecancermedicalscience  2016;10:663.
Background
Ethanol, a commonly available agent, has been used to successfully ablate cystic and solid lesions in the pancreas. The aim of this study is to investigate the effects of an ethanol injection into the porcine pancreas and observe the time-dependent image changes in the pancreatic parenchyma.
Methods
Pure ethanol was injected into the pancreatic tail using a 25-gauge EUS needle with direct ultrasound guidance under celiotomy: 1 mL and 2 mL were injected, respectively. The abdomen was closed after the injection. MRI was performed before the procedure, immediately after, and on postoperative day (POD) seven. Blood samples were taken before the procedure and on PODs one, three, five, and seven. The pigs were euthanised on POD seven.
Results
Immediately after the injection, linear high signal areas in the pancreatic tail on T2 and rounded speckled high signal areas on DWI images were detected in both animals, measuring 35 × 32 mm in the 1 mL injected pig and 42 × 38mm in the 2 mL injected pig. After POD seven, rounded high signal areas were noted on T2 images, measuring 22 × 18 mm and 36 × 28 mm respectively. On POD one, the 1 mL injected animal had a 53% elevation in serum amylase while the 2 mL injected animal had a 66% elevation. Histologically, cystic and necrotic changes in the parenchyma were observed, measuring 23 × 22 mm and 40 × 35 mm respectively.
Conclusions
Our results, which are limited to normal pancreas, suggested that a 1 mL injection caused localised changes within the pancreas while a 2 mL injection induced more widespread changes beyond the pancreas. The effective area of ethanol was widespread immediately after injection, and then the area was reduced with cystic and necrosis changes.
doi:10.3332/ecancer.2016.663
PMCID: PMC4990054  PMID: 27594908
ethanol injection; pancreas; porcine model; ultrasound; magnetic resonance imaging
25.  Veno-occlusive disease nurse management: development of a dynamic monitoring tool by the GITMO nursing group 
ecancermedicalscience  2016;10:661.
Veno-occlusive disease (VOD) is a complication arising from the toxicity of conditioning regimens that have a significant impact on the survival of patients who undergo stem cell transplantation. There are several known risk factors for developing VOD and their assessment before the start of conditioning regimens could improve the quality of care. Equally important are early identification of signs and symptoms ascribable to VOD, rapid diagnosis, and timely adjustment of support therapy and treatment. Nurses have a fundamental role at the stages of assessment and monitoring for signs and symptoms; therefore, they should have documented skills and training. The literature defines nurses’ areas of competence in managing VOD, but in the actual clinical practice, this is not so clear. Moreover, there is an intrinsic difficulty in managing VOD due to its rapid and often dramatic evolution, together with a lack of care tools to guide nurses. Through a complex evidence-based process, the Gruppo Italiano per il Trapianto di Midollo Osseo (GITMO), cellule staminali emopoietiche e terapia cellulare nursing board has developed an operational flowchart and a dynamic monitoring tool applicable to haematopoietic stem cell transplantation patients, whether they develop this complication or not.
doi:10.3332/ecancer.2016.661
PMCID: PMC4990055  PMID: 27594906
veno-occlusive disease; stem cell transplantation; nurse management; assessment; monitoring

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