Showing papers in "Ecancermedicalscience in 2013"

Oestrogen receptors in breast cancer: basic mechanisms and clinical implications.

Abstract: Since the discovery of the connection between ovarian hormones and breast cancer, endocrine therapy has been an integral adjuvant treatment for patients with hormone-dependent breast cancers. Oestrogen receptor (ER) plays a central role in mediating the effects of endogenous hormones and therapeutic agents. ER serves as a prognostic marker for responsiveness to endocrine therapy and is targeted either directly by selective oestrogen receptor modulators (SERMs) and pure antagonists or indirectly by aromatase inhibitors (AIs) that block oestrogen production. A significant number of ER-positive patients, however, fail to respond to therapy or develop resistance over time. This review focuses on the current understanding of ER functions and recent advances in genomic technologies and research that have provided a global perspective on hormone and ER activity and led to a number of significant discoveries, including the roles of co-regulatory factors and non-coding RNAs. Mechanistic insights into normal ER functions and therapeutic actions of SERMs and AIs will enable the development of better predictive markers and more effective target mechanisms and ultimately facilitate improvements in disease outcomes and patient survival.

The role of surgical resection in patients with brain metastases

Abstract: Brain metastasis is a devastating complication of systemic malignancy that affects a considerable number of cancer patients. The appearance of brain metastases is often considered to be a sign of poor prognosis; in patients with brain metastases poor survival time has been reported in the literature. Therefore, treatment of these brain lesions in cancer patients is important for quality of life, providing local tumour control, preventing death from neurological causes, and improving survival, although potentially only in a minority of patients. Surgical resection of brain metastases has been the cornerstone treatment in select patients. Careful patient selection, the use of appropriate surgical techniques, and surgical adjuncts are the major determinants of favourable outcome in patients undergoing resection of brain metastases. In this review, we explain the role of surgical resection in the treatment of patients with brain metastases with consideration of patient selection, surgical techniques and the use of intraoperative adjuncts.

Cancer incidence in Rabat, Morocco: 2006–2008

Abstract: Introduction: No population-based data of cancer incidence from Morocco have been published before. This is the first report of cancer incidence in Rabat from a population-based cancer registry for the period 2006–2008. Materials and methods: The cancer registry collects data on all new cases of cancer diagnosed in the resident population of the Rabat area. Data collection is an active process involving visits by registry staff to all data sources, essentially hospitals, pathological laboratories, and private clinics in Rabat. Results: A total of 2,473 new cases of cancer were registered among residents in Rabat during the period 2006–2008. The overall world age-standardised rate (ASR) for all sites combined was 136.6/100,000 for men and 114.5/100,000 for women. The most frequently diagnosed malignancies in males were lung cancer (19.0%, ASR 24.8/10 5 ), followed by prostate cancer (15.5%, ASR 22.9/10 5 ), colorectal cancer (8.8%,

Antiemetic activity of volatile oil from Mentha spicata and Mentha × piperita in chemotherapy-induced nausea and vomiting.

Abstract: Background: This study is aimed at determining the efficacy of Mentha spicata (M. spicata) and Mentha A� piperita (M. A� piperita) in preventing chemotherapy-induced nausea and vomiting (CINV). Methods: This was a randomised, double-blind clinical trial study. Prior to the study, patients were randomly assigned into four groups to receive M. spicata or M. A� piperita. Statistical analysis included the I�22 test, relative risk, and Student's t-test. Fifty courses were analysed for each group that met our eligibility criteria. The treatment and placebo groups applied essential oils of M. spicata, M. A� piperita, or a placebo, while the control group continued with their previous antiemetic regimen. Patients or guardians recorded the number of emetic events, the intensity of nausea over 20 h of chemotherapy, as well as any possible adverse effects that occurred during this time. Results: There was a significant reduction in the intensity and number of emetic events in the first 24 h with M. spicata and M. A� piperita in both treatment groups (p < 0.05) when compared with the control and no adverse effects were reported. The cost of treatment was also reduced when essential oils were used. Conclusion: M. spicata or M. A� piperita essential oils are safe and effective for antiemetic treatment in patients, as well as being cost effective. © the authors licensee ecancermedicalscience.

Breast cancer brain metastases: new directions in systemic therapy

Abstract: The management of patients with brain metastases from breast cancer continues to be a major clinical challenge. The standard initial therapeutic approach depends upon the size, location, and number of metastatic lesions and includes consideration of surgical resection, whole-brain radiotherapy, and stereotactic radiosurgery. As systemic therapies for control of extracranial disease improve, patients are surviving long enough to experience subsequent progression events in the brain. Therefore, there is an increasing need to identify both more effective initial treatments as well as to develop multiple lines of salvage treatments for patients with breast cancer brain metastases. This review summarises the clinical experience to date with respect to cytotoxic and targeted systemic therapies for the treatment of brain metastases, highlights ongoing and planned trials of novel approaches and identifies potential targets for future investigation.

Tumour dormancy and clinical implications in breast cancer

Abstract: The aim of adjuvant therapy in breast cancer is to reduce the risk of recurrence. Some patients develop metastases many years after apparently successful treatment of their primary cancer. Tumour dormancy may explain the long time between initial diagnosis and treatment of cancer, and occurrence of relapse. The regulation of the switch from clinical dormancy to cancer regrowth in locoregional and distant sites is poorly understood. In this review, we report some data supporting the existence of various factors that may explain cancer dormancy including genetic and epigenetic changes, angiogenic switch, microenvironment, and immunosurveillance. A better definition and understanding of these factors should allow the identification of patients at high risk of relapse and to develop new therapeutic strategies in order to improve prognosis.

Progesterone receptor isoforms A and B: new insights into the mechanism of progesterone resistance for the treatment of endometrial carcinoma

Abstract: Progesterone therapy is an effective treatment for atypical endometrial hyperplasia and early endometrial carcinoma (EC). However, progesterone resistance is the main obstacle to the success of conservative treatment in women with type I EC and remains a major clinical challenge. Studies indicate that progesterone and progesterone receptors (PRs) play a significant role in both normal and neoplastic endometria. Most EC arises in the epithelial cells of the endometrial glands, and a large body of in vitro evidence suggests that the absence or reduced expression of PR isoform B might result in the failure of progesterone treatment and lead to aberrant PRB-mediated signalling in EC cells. A recently developed in vivo knockout mouse model suggests that enhanced DNA methylation decreases the level of stromal PR isoform A and that this is also a main contributor to progesterone resistance in EC cells. The endometrial stroma within the EC might create a microenvironment that determines how epithelial-derived cancer cells respond to progesterone. This novel study opened a new avenue for research seeking to clarify the mechanisms that regulate the specific PR isoforms that are associated with the stromal cell responses to progesterone and has led to new understanding of both endometrial cell-specific and mechanical contributions of the stroma to EC development.

Transoral robotic surgery in the management of head and neck tumours

Abstract: The article reviews the use of robotic technology for head and neck tumours. The authors discuss the development of transoral robotic surgery (TORS), the current status of the technology, and the set-up in the operating room. The article provides a review of the literature, highlighting the applications, advantages, functional outcomes, and disadvantages of TORS for each anatomic subsite (oropharynx, hypopharynx, larynx, parapharyngeal space, and skull base). New challenges related to reconstruction are also presented. Overall early functional and oncologic outcome data are promising; further long-term prospective trials are still needed to confirm the oncological safety of TORS.

Highlights from the Third International Central Nervous System Germ Cell Tumour symposium: laying the foundations for future consensus.

Abstract: The Third International Central Nervous System (CNS) Germ Cell Tumour (GCT) Symposium brought together over 100 delegates from all over the world to learn about the latest developments in these tumours and discuss future strategies for their management. Some areas of consensus were agreed upon, and controversies were discussed. Among these, the classification of GCTs and the surgical approach to their management were among the greatest areas of difference between different parts of the world. The need for radiotherapy (RT) as a part of standard first-line management for all malignant CNS GCTs was agreed, as well as the need for additional chemotherapy to maximise the cure in nongerminomatous malignant GCTs; the benefit of the addition of chemotherapy in localised germinoma to reduce the RT burden was also accepted as a good practice. The potential of biological parameters to assist the future diagnosis, treatment stratification, and disease monitoring for CNS GCTs was discussed. Such biological parameters may also represent targets for the development of novel therapies. The need for further collaboration between groups engaged in biological studies was agreed. The merits of proton beam RT were debated, and the importance of mitigating the long-term side effects of the treatment was underlined by a session on late effects.

Robotic bilateral inguinal lymphadenectomy in penile cancer, development of a technique without robot repositioning: a case report

Abstract: Introduction: Inguinal lymphadenectomy is the treatment of choice for patients with penile cancer and inguinal lymph node metastases. We describe the performance of the robotic bilateral inguinal lymphadenectomy technique without repositioning the robot in a patient with penile carcinoma and high risk for nodal metastases and no palpable lymph nodes. Materials and methods: A 64-year-old male patient was diagnosed with penile cancer (TNM: T3 N 0 M 0) and underwent a total penectomy with perineal urethrostomy. We performed a robotic bilateral inguinal lymphadenectomy four weeks after the penectomy. Results: The entire procedure was performed with the robot-assisted technique. The operative time, median estimated blood loss, and hospital stay was 360 min, 100 ml (50 ml in the right side and 150 ml in the left side), and three days, respectively. Metastatic nodes were present in both inguinal regions, with a yield of 19 lymph nodes on the right and 14 on the left. The patient presented with a left-side lymphocele that was drained at follow-up. No other complications were reported. Conclusion: Robotic bilateral inguinal lymphadenectomy secondary to penile cancer is feasible, safe, and provides a good performance. Prospective studies are required to include a larger number of patients and long-term monitoring to assess the results of this procedure in comparison with open and laparoscopic techniques.

Vitamin supplement consumption and breast cancer risk: a review

Abstract: Background: Breast cancer is the most frequently diagnosed cancer globally, and studies provide contradictory results about the possible effects of vitamin supplementation to reduce cancer risk. Our aim was to conduct a review to better investigate whether vitamin supplements given orally modify breast cancer risk. Methods: We conducted a comprehensive, systematic bibliographic search of the medical literature to identify relevant studies. Case-control, cohort studies, and randomised controlled trials (RCTs) published up to August 2013 that reported cancer risk estimates for vitamin supplementation were included. For each study, we retrieved study characteristics, study population, exposure evaluation, and risk estimates. Results: We identified 26 studies (14 cohort, 11 case-control, and one RCT) and overall, we found 104 estimates. We grouped all the estimates into six supplementation categories: vitamin A and beta-carotene, B-group vitamins and folic acid, vitamin C, vitamin D, vitamin E, and multivitamins. Only a few studies showed a statistically significant association between the consumption of supplemental vitamins and the occurrence of breast cancer, and most of the significant estimates were found in case-control studies. The results found in prospective studies seem to be in the opposite direction. Conclusion: The role of vitamin supplements in preventing breast cancer still remains unclear, considering our review. Although biologic mechanisms exist to support the anticancer effects of vitamins, there is no clear evidence for an effect in cancer prevention for vitamin supplements. Further investigations are warranted to elucidate the mechanisms by which vitamin supplementation can modify breast cancer development.

Prognostic factors in early-stage ovarian cancer

Abstract: The purpose of this study was to identify the main prognostic factors in patients with early-stage epithelial ovarian cancer. Data were extracted from 222 patients with initial stage (I-IIA) invasive epithelial ovarian cancer treated with primary surgery followed or not followed by adjuvant therapy, from 1 January 1980 to 31 December 2008, at the Division of Obstetrics and Gynecology, Spedali Civili, Brescia, Italy; the median follow-up was 79 months (SD ± 35,945, range 20-250 months). The negative prognostic factors that were statistically significant (p<0.050) in univariate analysis were grade 2, 3, and X (clear cell in our study); stage IB, IC, IIA; positive peritoneal cytology, age equal to/greater than 54; dense adhesions; capsule rupture (pre-operative or intra-operative) and endometrioid histotype (only for disease-free survival (DFS)). Positive cytology was strongly associated with peritoneal relapses, while adhesions were associated with pelvic relapses. A positive prognosis was associated with the mucinous histotype. Conservative treatment had been carried out in 52% of patients under 40 years of age, and we detected only two relapses and three completions of surgery after a few weeks among 31 women in total. Our study indicated a possible execution in patients with patients with cancer stage IA G1-G2 (p=0.030) or IC G1 (p=0.050), provided well staged. Adjuvant chemotherapy improved the survival of cancers that were not IA G1. The positive prognostic role of taxanes must be emphasised, when used in combination with platino.

Incidence and management of infections in patients with acute leukemia following chemotherapy in general wards

Abstract: We hypothesise that treating patients with acute leukaemia in general wards, with proper hygienic and sanitary practices, would result in the minimum utilisation of resources as compared with the corresponding patients receiving ICU support. For this study, the acute leukaemia patients on induction chemotherapy were kept in general wards and observed for the incidence of neutropenia, resultant neutropenic febriles, the causative organism, and the effect of empirical antimicrobial treatment protocol on the outcome of such infections. Prophylactic anti-fungal therapy and cotrimoxazole therapy improved the outcome of infections. The therapy of neutropenic fever and infections must be adapted according to the risk factors and should include early empiric antifungal therapy. It was observed that the treatment of such patients in general wards could be managed effectively, with the added advantage of optimum utilisation of resources and in a patient-friendly environment, at a reasonable cost to the patients.

Real-world experience with colorectal cancer chemotherapies: patient web forum analysis

Abstract: Background: In contrast to clinical trials, patient web forums provide a unique opportunity for patients to spontaneously post their experiences and thoughts about diseases and treatments. This study explored the impact of colorectal cancer (CRC) treatments in these forums. Methods: This was a systematic cross-sectional qualitative analysis. Two active CRC web forums were identified based on four criteria: active for ≥five years, >12,000 total posts, >20 individuals currently browsing, and ≥10 new posts/day. All relevant threads (set of messages focusing on a topic) relating to treatment posted in July and December 2010 and February to March 2011 were reviewed and coded using MaxQDA software. A content analysis was performed identifying key themes. Results: The threads included 1522 posts by 264 individuals. Demographics were identified for 83% of the posters. Of these, 83% were CRC patients and 17% were family members; 76% were females, and the mean patient age was 49 years. The majority had advanced cancer (44% stage IV or metastatic, 40% stage III). The most common themes were side effects (62.3% of posts), treatment response (13%), and impact on personal, social, and work lives, and emotional distress (23.9%). The posters came to the online forums to have an emotional outlet, share experience, and seek advice. The emotional impacts primarily exemplified resilience and positive coping strategies. Formal knowledge regarding the likelihood of treatment response, magnitude of benefit, or side effects was lacking, which lead to uncertainty and anxiety. However, patients expressed appreciation for the availability of treatment options and the hope they provide.

The role of the robotic technique in minimally invasive surgery in rectal cancer

Abstract: Laparoscopic rectal surgery is feasible, oncologically safe, and offers better short-term outcomes than traditional open procedures in terms of pain control, recovery of bowel function, length of hospital stay, and time until return to working activity. Nevertheless, laparoscopic techniques are not widely used in rectal surgery, mainly because they require a prolonged and demanding learning curve that is available only in high-volume and rectal cancer surgery centres experienced in minimally invasive surgery. Robotic surgery is a new technology that enables the surgeon to perform minimally invasive operations with better vision and more intuitive and precise control of the operating instruments, promising to overcome some of the technical difficulties associated with standard laparoscopy. The aim of this review is to summarise the current data on clinical and oncological outcomes of minimally invasive surgery in rectal cancer, focusing on robotic surgery, and providing original data from the authors’ centre.

Borderline tumours of the ovary, current controversies regarding their diagnosis and treatment

Abstract: Borderline ovarian tumours generally affect women of reproductive age. The positive prognosis is related to the fact that over 80% of cases are diagnosed at an early stage of the disease. Although radical surgery is the standard of care for this disease, fertility-sparing surgery can be performed in selected cases. Since it was first described in 1929, the knowledge of the molecular and histologic characteristics has been significantly improved. In this review, advances in the clinical behaviour, pathologic characteristics, prognostics factors, and different strategies of treatment are discussed.

Heterogeneity of circulating epithelial tumour cells from individual patients with respect to expression profiles and clonal growth (sphere formation) in breast cancer.

Abstract: Background: The detection of tumour cells circulating in the peripheral blood of patients with breast cancer is a sign that cells have been able to leave the primary tumour and survive in the circulation. However, in order to form metastases, they require additional properties such as the ability to adhere, self-renew, and grow. Here we present data that a variable fraction among the circulating tumour cells detected by the Maintrac ® approach expresses mRNA of the stem cell gene NANOG and of the adhesion molecule vimentin and is capable of forming tumour spheres, a property ascribed to tumour-initiating cells (TICs). Patients and methods: Between ten and 50 circulating epithelial antigen-positive cells detected by the Maintrac approach were selected randomly from each of 20 patients with breast cancer before and after surgery and were isolated using automated capillary aspiration and deposited individually onto slides for expression profiling. In addition, the circulating tumour cells were cultured without isolation among the white blood cells from 39 patients with breast cancer in different stages of disease using culture methods favouring growth of epithelial cells. Results: Although no epithelial cell adhesion molecule (EpCAM)-positive cells expressing stem cell genes or the adhesion molecule vimentin was detected before surgery, 10%–20% of the cells were found to be positive for mRNA of these genes after surgery. Tumour spheres from circulating cells of 39 patients with different stages of breast cancer were grown without previous isolation in a fraction increasing with the aggressivity of the tumour. Summary: Here we show that among the peripherally circulating tumour cells, a variable fraction is able to express stem cell and adhesion properties and can be grown into tumour spheres, a property ascribed to cells capable of initiating tumours and metastases.

The tumour is not enough or is it? Problems and new concepts in the surgery of cerebral metastases.

Abstract: Cerebral metastases are the most frequent cerebral tumours. Surgery of cerebral metastases plays an indispensible role in a multimodal therapy concept. Conventional white-light, microscopy assisted microsurgical and circumferential stripping of cerebral metastases is neurosurgical standard therapy, but is associated with an extraordinarily high recurrence rate of more than 50% without subsequent whole-brain radiotherapy. Therefore, neurosurgical standard therapy fails to achieve local tumour control in many patients. The present conceptual paper focuses on this issue and discusses the possible causes of the high recurrence rates such as intraoperative dissemination of tumour cells or the lack of sharp delimitation of metastases from the surrounding brain tissue resulting in incomplete resections. Adjuvant whole-brain radiotherapy reduces the risk of local and distant recurrences, but is associated with a well-documented impairment of neurocognitive function. New surgical strategies, such as supramarginal or fluorescence-guided resection, address the possibility of infiltrating tumour parts to achieve more complete resection of cerebral metastases. Supramarginal resection was shown to significantly reduce the risk of a local recurrence and prolongs two-year survival rates. Furthermore, radiosurgery in combination with surgery represents a promising approach.

Clinical evidence for the use of aspirin in the treatment of cancer.

Abstract: Although the anti-cancer effects of aspirin were first identified in pre-clinical models four decades ago, a clear role for the drug in either the prevention or treatment of cancer has not been established. Concerns about toxicity, particularly major haemorrhage, and a lack of randomised evidence demonstrating efficacy have limited its use in primary prevention; there was also doubt that a simple aspirin could have a significant therapeutic effect against established malignancy. Three new pieces of evidence: a series of meta-analyses focusing on cancer outcomes from randomised-controlled trials designed to assess the vascular benefits of daily aspirin; the first positive results from a randomised-controlled trial designed to demonstrate that aspirin can prevent cancer in those with a hereditary predisposition; and observational data showing that aspirin use after a cancer diagnosis improves both cancer mortality and overall survival; have led to a re-evaluation of aspirin as a potential anti-cancer agent both for the prevention and treatment of cancer.

"Intracystic papillary breast cancer: a clinical update".

Abstract: Introduction: Intracystic (encysted) papillary cancer (IPC) is a rare entity of breast cancer accounting for approximately (1–2%) of all breast tumours [1] , usually presenting in postmenopausal women and having an elusive natural history. The prediction of the biological behaviour of this rare form of breast cancer and the clinical outcome showed its overall favourable prognosis; however, its consideration as a form of ductal carcinoma in situ with non-invasive nature is to be reconsidered as it has been shown to present histologically with invasion of basement membrane and even metastasis [2] . The objective of this review is to shed some light on this rare, diagnostically challenging form of breast cancer, including its radiological, histological, and molecular characteristics and its pathological classification. The final goal is to optimize the clinical management including the role of sentinel lymph node biopsy (SLNB), general management with adjuvant radiotherapy (RT), mammary ductoscopy, and hormonal treatment. Methods: A literature review, facilitated by Medline, PubMed, and the Cochrane database, was carried out using the terms ‘Intracystic (encysted) papillary breast cancer’. Results: Intracystic papillary breast cancer (IPC) is best managed in the context of a multidisciplinary team. Surgical excision of the lump with margins in excess of 2 mm is considered satisfactory. Sentinel lymph node biopsy (SLNB) is recommended as data have shown the possibility of the presence of invasive cancer in the final histology. RT following IPC alone is of uncertain significance as this form of cancer is usually low grade and rarely recurs. However, if it is associated with DCIS or invasive cancer and found in young women, radiotherapy may be prudent to reduce local recurrence. Large tumours, centrally located or in cases where breast conserving surgery is unable to achieve a favourable aesthetic result, a skin sparing mastectomy with the opportunity for immediate reconstruction can be offered. Adjuvant endocrine therapy may be suggested as almost certainly these tumours are hormonal positive. Conclusion: Further research is required to determine the role of adjuvant radiotherapy and endocrine therapy in IPC. Understanding the low-grade nature of this form of breast cancer allows treatment options to be less radical and safely omitted.

Primary intraosseous squamous cell carcinoma arising from an odontogenic keratocyst: a case report and literature review

Abstract: Primary intraosseous squamous cell carcinoma (PIOSCC) derived from an odontogenic keratocyst (OKC) is a rare malignant neoplasm of the jaws, which is locally aggressive with quite poor prognosis. The incidence of carcinomas arising in odontogenic cysts was reported to be approximately 1–2/1000. The number of well-documented cases of PIOSCC ex OKC is extremely small; hence, no sufficient incidence data are available in the literature. Overall, the survival rate of an individual, which is a period of two years, is very poor, and this can be attributed to the delayed diagnosis. But knowledge of the histopathological and immunohistological features of PIOSCC allows accurate and early diagnosis of the lesion so that an early and appropriate treatment can be instituted for better prognosis. The following report describes an extremely rare case of PIOSCC of the mandible derived from an OKC in a 20-year-old female patient.

A clinical update on massive ovarian oedema – a pseudotumour?

Abstract: Objective Benign massive ovarian oedema is a rare clinical entity arising from the ovaries, and it poses a significant clinical challenge as it can be easily mistaken for neoplasm. Due to the lack of pathognomonic clinical features or characteristic hallmarks on non-invasive diagnostic modalities and the dependence on the final histopathology, the efforts of the surgeon have been deviated from performing fertility-sparing surgery on young women. The lack of standardised guidelines due to the rarity of this condition calls for a review of the literature to enable the clinician to formulate treatment guidelines. Methods and material A Medline search on the PubMed database for literature published in English from 1969 to 2011 was done using the keywords 'massive ovarian oedema, massive ovarian oedema case report or case series, and pseudotumour of ovary'. A total of 177 women who had undergone a variety of treatments were retrieved. We also report the management options we used for four women presenting to us between August 2000 and October 2011, as well as a review of the literature. Result A total of 177 cases of massive ovarian oedema were identified. Out of these cases 151 (85.3%) were primary massive ovarian oedema; secondary massive ovarian oedema was identified in 26 (14.7%) cases. A salpingo-oophorectomy was done in 145 (81.9%) cases, 12 (6.8%) cases had an abdominal hysterectomy with bilateral salpingo-oophorectomy. A total of 76 (42.9%) cases intraoperatively were found to have ovarian torsions, and one patient with primary massive ovarian oedema had ascites. Conservative treatment was carried out in 20 (11.3%) patients; 14 of these had a wedge biopsy with frozen section and with or without ovarian suspension, one patient had diagnostic laparotomy, and five cases had only ultrasonographic or magnetic resonance imaging monitoring and symptomatic treatment. The four cases treated at the regional cancer institute from 2000 to 2011 revealed that the first three cases had salpingo-oophorectomy and the fourth case received a successful conservative treatment. Conclusion The majority of massive ovarian oedemas will respond to judicious use of intraoperative wedge resection and frozen section for the confirmation of diagnosis. The detorsion and transfixation of the ovary or partial debulking and drainage of fluid accumulated in the cyst may be more appropriate to preserve hormonal function and fertility in these young women.

Vascular endothelial growth factor expression and inhibition in uveal melanoma cell lines

Abstract: Background: Uveal melanoma (UM) is a disease that affects approximately five people per million in the United States. This disease metastasises predominantly to the liver, and treatment options following the clinical detection of these sequelae are limited. Vascular endothelial growth factor-A (VEGF-A) is the primary activator of tumour angiogenesis and functions by binding to VEGF-Receptor 2 (VEGF-R2) and is often required for tumour growth beyond 2–3 mm. The purpose of this study was to investigate the expression of VEGF-A and the primary VEGF-R2 in three UM cell lines. Furthermore, we investigated the effects of VEGF-A inhibition on receptor activation and production of other cytokines. Finally, the effects of VEGF-A inhibition on the proliferation, migration, and invasion in the cell lines were ascertained.

Highlights from the 13th St Gallen International Breast Cancer Conference 2013. Access to innovation for patients with breast cancer: how to speed it up?

Abstract: The recognition that early breast cancer is a spectrum of diseases each requiring a specific systemic therapy guided the 13th St Gallen International Breast Cancer Consensus Conference [1]. The meeting assembled 3600 participants from nearly 90 countries worldwide. Educational content has been centred on the primary and multidisciplinary treatment approach of early breast cancer. The meeting culminated on the final day, with the St Gallen Breast Cancer Treatment Consensus, established by 40-50 of the world's most experienced opinion leaders in the field of breast cancer treatment. The major issue that arose during the consensus conference was the increasing gap between what is theoretically feasible in patient risk stratification, in treatment, and in daily practice management. We need to find new paths to access innovations to clinical research and daily practice. To ensure that continued innovation meets the needs of patients, the therapeutic alliance between patients and academic-led research should to be extended to include relevant pharmaceutical companies and drug regulators with a unique effort to bring innovation into clinical practice. We need to bring together major players from the world of breast cancer research to map out a coordinated strategy on an international scale, to address the disease fragmentation, to share financial resources, and to integrate scientific data. The final goal will be to improve access to an affordable, best standard of care for all patients in each country.

Assessment of the clinical utility of the Gail model in estimating the risk of breast cancer in women from the Indian population.

Abstract: Introduction: Breast cancer screening programmes are based on various risk models to assess the risk of breast cancer in the general population. The aim of the present study is to predict the efficacy of the Gail model (GM) in the Indian population. We did a retrospective calculation of the Gail score from the hospital records of patients with breast cancer and benign breast disease. Materials and methods: The Gail score was calculated in three groups. The three groups were made up of 104 patients with confirmed breast cancer (Group A), 100 patients with confirmed benign breast diseases (Group B), and 100 patient attendants (Group C). Statistical analysis: The data analysis was done using SPSS 15.0, Medcal 9.0.1. Results: The median Gail score in the three groups of patients was 7.5±3.04 in patients with breast cancer, 8.2±1.4 in patients with benign breast diseases, and 7.8±1.7 in normal people. The median Gail score was lower in patients with breast cancer when compared with normal people. Conclusion: The GM is not useful in identifying the risk of breast cancer in Indian women. There is a need for further studies to evaluate other genetic and environmental factors to create an appropriate model for the Indian population.

The impact of the Oncotype DX Recurrence Score on treatment decisions and clinical outcomes in patients with early breast cancer: the Maccabi Healthcare Services experience with a unified testing policy

Abstract: The Oncotype DX Recurrence Score is a validated prognosticator in oestrogen receptor positive (ER+) breast cancer. Our retrospective analysis of a prospectively defined cohort summarises the clinical implications associated with Oncotype DX testing according to the Maccabi Healthcare Services (MHS) policy. The MHS eligibility criteria for testing included ER+ N0/pN1mic invasive tumours, discussion of test implications with an oncologist, ductal carcinoma 0.6–1 cm Grade 2–3, HER2 negative ductal carcinomas with 1.1–4.0 cm Grade 1–2, or lobular carcinoma. Large (> 1 cm) Grade 3 tumours could have grade reassessed. We linked Recurrence Score results with patients’ information and used chi-squared tests to assess the associations thereof. Between January 2008 and December 2011, tests were performed on 751 patients (MHS-eligible, 713); 54%, 38%, and 8% of patients had low, intermediate, and high Recurrence Score results, respectively. Recurrence Score distribution varied significantly with age (P = 0.002), with increasing Recurrence Score values with decreasing age. The proportion of patients with high Recurrence Score results varied by grade/size combination and histology, occurring in 32% of small (≤ 1 cm) Grade 3 and 3% of larger (1.1–4 cm) Grade 1 ductal tumours and only in 2% of lobular carcinomas. Chemotherapy was administered to 1%, 13%, and 61% of patients with low, intermediate, and high Recurrence Score results, respectively (P < 0.0001), but only to 2% of intermediate score patients ≥ 65 years. Luteinising-hormone-releasing hormone agonists with tamoxifen were used in 27% of low Recurrence Score patients ≤ 50 years. With a median follow-up of 26 months, no systemic recurrences were documented, whereas four patients exhibited locoregional recurrences. In summary, in this low-to-moderate risk patient population, testing identified 46% of patients as intermediate/high risk. Treatment decisions were influenced by Recurrence Score results and patients’ age. The current MHS policy seems to achieve the goal of promoting chemotherapy use according to the test results in a prespecified patient population.

Oncoplastic surgery in the treatment of breast cancer.

Abstract: Advances in reconstructive breast surgery with new materials and techniques now allow us to offer our patients the best possible cosmetic results without the risks associated with oncological control of the disease. These advances, in both oncological and plastic surgery, have led to a new specialisation, namely oncoplastic breast surgery, which enables us to undertake large resections and, with advance planning, to prevent subsequent deformities. This is particularly important when more than 30% of the breast volume is removed, as it allows us to obtain precise information for conservative surgery according to the site of the lesion, and also allows us to set the boundary between conservative surgery and mastectomy. Given the existence of new alloplastic materials and new reconstructive techniques, it is essential for our patients that surgeons involved in breast cancer treatment are trained in both the oncological as well as the reconstructive and aesthetic fields, to enable them to provide the best loco-regional treatment with the best cosmetic results.

Surgical management of melanoma: an EORTC Melanoma Group survey

Abstract: Objectives: The objective of the article is to explore the surgical practices and views in the treatment of melanoma within members and non-members of the EORTC Melanoma Group (MG) during the years 2003–2005. Methods: An e-mail questionnaire (see appendix) developed within the EORTC MG was sent to all melanoma units (MUs) of the EORTC (180) and to selected international centres between 2003 and 2005. The questionnaire investigated the different practices regarding surgical management of melanoma patients at all stages. Results: A total of 75 questionnaires were returned from centres in Europe (70), Israel (3), Australia (1) and the United States (1). Resection margins on primary melanoma vary according to AJCC 2002 staging. Sixty three of 75 MUs perform Sentinel node biopsy. Modified radical neck dissection is performed in 82% of MUs for macrometastases and in 80% of MUs for micrometastases. Most MUs surveyed perform all three levels of Berg axillary dissection whether for macrometastases (79%) or micrometastases (62%). An ilio inguinal-obturator dissection is proposed with macrometastases (41% of MUs), whereas 33% of MUs perform a pelvic dissection only if the Cloquet node is positive. Twenty five of 75 MUs perform an isolated limb perfusion with a therapeutic indication; three also as an adjuvant. The majority of MUs perform surgery for distant metastases including superficial (53 of 75 [71%]) or solitary visceral metastases (52 of 75[69%]) or for palliation (58 of 75[77%]). Conclusion: The adequacy of surgery appears to be the most important milestone in the therapeutic approach of melanoma. Even if surgery is fundamental in the different stages of the disease, there is quite a variability concerning the extension of the surgical treatment related to primary and lymphnodal disease. Phase III randomised trials have shown that wide margins, elective lymph node dissections, and prophylactic isolated limb perfusions have not improved survival and cannot be considered the standard of care in the routine management of primary melanoma. The surgical subgroup of the EORTC Melanoma Group is developing a new version of the surgical survey questionnaire including new treatment modalities like isolated limb infusion and electrochemotherapy, which were not frequently in use some years ago, to obtain new data to be compared to the nearly ten-year-old data.

International Rare Cancers Initiative (IRCI).

Abstract: We declare that we have no conflicts of interest. There is no internationally agreed definition of a rare cancer. In Europe, rare diseases are often defined as those with a prevalence of <50/100,000 [1]. In the US, the Orphan Drug Designation Program defines rare diseases as those affecting <200,000 people in the total US population, equivalent to a prevalence of 64/100,000 [1]. The problem with both these definitions is that they are based on prevalence, which does not properly reflect the health burden of incident diseases such as cancer. RARECARE more usefully defines rare cancers as those with an incidence of <6/100,000/year [3]. Using this definition, the combined annual incidence rate of all rare cancers in Europe is about 108 per 100,000, corresponding to 541,000 new diagnoses annually or 22% of all cancer diagnoses. This is more than any single common cancer. And returning to prevalence, about 4,300,000 patients are living today in the European Union with a diagnosis of a rare cancer, 24% of the total cancer prevalence. Unfortunately, the average outcome for patients with a rare cancer is inferior to those with more common cancers [1]. One factor contributing to this is the lack of evidence upon which to base treatment, so in an attempt to address this issue, the International Rare Cancers Initiative (IRCI) was established early in 2011. IRCI is a joint initiative between the National Institute for Health Research Cancer Research Network (NCRN), Cancer Research UK (CR-UK), the National Cancer Institute (NCI) and the European Organisation for Research and Treatment of Cancer (EORTC). The objective of this initiative is to facilitate the development of international clinical trials for patients with rare cancers in order to boost the progress of new treatments for these patients. For the purpose of IRCI, ‘rare’ has been broadly defined as an incidence of <2 per 100,000. Occasionally, rare clinical scenarios with less rare cancers have also been considered, e.g. relapsed anal cancer. To date, IRCI has excluded rare molecular sub-types of common cancers; however, a rare molecular sub-type could be considered if it is a distinct, prospectively identifiable rare sub-group with a strong rationale for separate research, rather than inclusion as a molecular stratum in a mainline trial. Priority has been given to cancers with potential for an interventional trial (usually randomised) rather than an audit, registry or non-trial tissue collection. The initiative hopes to encourage the use of innovative methodologies, such as Multi-Arm Multi-Stage (MAMS) trial designs and Bayesian statistics, to maximise the potential for answering research questions and to identify and overcome barriers to international trials to allow agreed IRCI trials to run smoothly. At the outset of the initiative clinical communities associated with each partner organisation were asked to identify rare cancers where there was enthusiasm for international collaborations and the potential for development of an interventional clinical trial. It was not possible to take forward every rare cancer type suggested, but where interests coincided in at least two of the partner organisations, and the IRCI Board could see potential for research development, IRCI groups were formed. The following nine rare cancers have formed the core activities of IRCI to date: Salivary gland cancer, Anaplastic thyroid cancer, Small bowel adenocarcinoma, Gynaecological sarcoma, Fibrolamellar hepatocellular carcinoma, Penile cancer, Thymoma, Ocular melanoma, Relapsed/metastatic anal cancer. IRCI organises face-to-face meetings and teleconferences to allow potential clinical trial designs to be discussed and developed. Wherever possible these face-to-face meetings are run alongside international conferences that the leads and other experts are already likely to be attending. IRCI has been met with considerable enthusiasm by the international clinical community. Of the initial nine groups taken on by IRCI, seven are actively developing 10 clinical trials for submission to appropriate funding bodies. The IRCI Gynaecological Sarcoma Group has made great progress and in September 2012 the first IRCI study opened to recruitment - A phase III randomised trial of gemcitabine plus docetaxel followed by doxorubicin versus observation for uterus-limited, high grade uterine leiomyosarcoma (IRCI 001, ClinicalTrials.gov registration number {"type":"clinical-trial","attrs":{"text":"NCT01533207","term_id":"NCT01533207"}}NCT01533207). This IRCI study is led by Dr Martee Hensley (Memorial Sloan-Kettering Cancer Centre, MSKCC) and co-ordinated by the Gynecologic Oncology Group (GOG). It opened to recruitment at the MSKCC early in September 2012 and it is hoped that the first patient will be recruited to this study imminently. The study is currently being processed by the EORTC and Glasgow Clinical Trials Unit and is due to open to recruitment in Europe in the next few months. Ultimately, IRCI aims to open and recruit to international clinical trials for patients with rare cancers in order to boost the progress of new treatments for these patients and ultimately, improve outcomes. IRCI aims to do this by continuing to aid its existing groups, working through the issues of trial setup with the trials developed and taking on further rare cancer types (it is expected that two new rare cancer groups will be initiated in 2013 - relapsed Ewing’s sarcoma and Desmoplastic small round cell tumours). Additionally, IRCI may expand to involve other interested organisations. Finally, developing relationships with industry is a key objective.

Filgrastim XM02 (Tevagrastim®) after autologous stem cell transplantation compared to lenograstim: favourable cost-efficacy analysis

Abstract: Purpose: Granulocyte colony-stimulating factors (G-CSFs), filgrastim and lenograstim, are recognised to be useful in accelerating engraftment after autologous stem cell transplantation. Several forms of biosimilar non-glycosylated G-CSF have been approved by the European Medicines Agency, with limited published data supporting the clinical equivalence in peripheral blood stem cell mobilisation and recovery after autologous stem cell transplantation. Method: With the aim of comparing cost-effective strategies in the use of G-CSF after autologous stem cell transplantation, we retrospectively evaluated 32 patients consecutively treated with biosimilar filgrastim XM02 (Tevagrastim) and 26 with lenograstim. All patients received G-CSF (biosimilar or lenograstim) at a dosage of 5 mcg/kg/day subcutaneously from day 5 to absolute neutrophil count of 1500/mmc for three days. Results: The median time to absolute neutrophil count engraftment was 11 days for the filgrastim XM02 group and 12 days for the lenograstim group. As for platelets recovery, the median time was 12 days in both groups. The median number of G-CSF vials used for patients was 9.5 for Tevagrastim and 10.5 for lenograstim, reflecting a mean estimated cost of about 556.1 euros for Tevagrastim versus 932.2 euros for lenograstim (p < 0.001). The median days of febrile neutropenia were 1.5 and 1 for filgrastim XM02 and lenograstim, respectively. No adverse event related to the use of XM02 filgrastim was recorded. Conclusion: In our experience, filgrastim XM02 and lenograstim showed comparable efficacy in shortening the period of neutropenia after cytoreduction and autologous stem cell transplantation, with a favourable cost effect for filgrastim XM02.