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Contains fulltext : 200423.pdf (Publisher’s version ) (Closed access) BACKGROUND/AIM: Synovial sarcoma is a soft tissue sarcoma that tends to affect young adults. There are few reports on primary synovial sarcoma of the thyroid and the aim of this study was to document the clinical and pathological features of synovial sarcoma occurring at this site. CASE PRESENTATION: A retrospective review of a prospectively maintained database was performed to identify patients with synovial sarcoma of the thyroid treated at the Royal Marsden Hospital between 2000 and 2017. Five patients were identified that underwent initial surgical management of localized disease. The mean age at presentation was 38 years, and male to female ratio was 4:1. In 3 out of 5 cases, the diagnosis of synovial sarcoma was made on the post-operative excision specimen. Two of these patients were treated at our institution on the development of metastatic disease. We conducted a literature review and identified 12 previously reported cases of synovial sarcoma of the thyroid. CONCLUSION: Synovial sarcoma of the thyroid is rare and can be challenging to diagnose. The clinical presentation is typically indistinguishable from that of thyroid cancer and most cases are diagnosed post-operatively on an excision specimen. The clinical and pathological features are similar to synovial sarcoma arising at other sites. In our experience, the rarity of the diagnosis can lead to difficulty in establishing the correct diagnosis and determining the appropriate treatment pathway. It is important that physicians are aware of this diagnosis to facilitate prompt referral to a specialist centre, for specialist follow-up and treatment which is different to the thyroid cancer pathway.

Contains fulltext : 208930.pdf (Publisher’s version ) (Open Access) BACKGROUND/AIM: Epithelioid haemangioendothelioma (EHE) is a rare tumor with a wide spectrum of clinical behavior. There is no consensus on the role of local therapy in symptomatic, multi-focal disease. PATIENTS AND METHODS: A retrospective review of patients presenting to the Royal Marsden Hospital between January 2000 and December 2017 was conducted. RESULTS: Fifty-three patients with EHE were identified, of which 18 patients (34.0%) received local therapy, and 11 patients (20.8%) underwent active surveillance. A variety of local treatment modalities were used with few toxicities, and local recurrence was managed with other local treatments or systemic therapy. Distal disease progression was infrequent (n=4, 7.5%). Patients who developed pleural effusion (n=5, 9.4%) had poor outcome irrespective of treatment. CONCLUSION: Local therapy has a role in a selected patient group managed in a multidisciplinary setting, including patients with indolent disease, and patients with a solitary area of progression/symptomatic disease.

Contains fulltext : 203015.pdf (Publisher’s version ) (Open Access) BACKGROUND/AIM: Treatment options for patients with metastatic soft tissue sarcomas are limited. Re-challenge with a previously successful gemcitabine-based regimen is common. There are no published data to support this practice. PATIENTS AND METHODS: We conducted a retrospective search to identify patients re-challenged with gemcitabine-based chemotherapy (GBC) from 2003 to 2015. RESULTS: Twenty-nine patients re-challenged with gemcitabine were identified. The response rate for initial GBC was 55% (n=15) and for re-challenge GBC 26% (n=6). The median progression-free survival was 11.1 months (95%CI=7.2-11.9) for initial GBC and 5.3 months (95%CI=2.0-7.5) for re-challenge GBC. Overall survival following gemcitabine re-challenge was 12.2 months (95%CI=7.0-18.2). Twelve out of 26 evaluable patients (46%) treated with re-challenge GBC experienced grade 3-4 adverse events (CTCAE 4.03) with 31% (n=8) of patients requiring dose reduction. CONCLUSION: In selected patients, gemcitabine re-challenge can be considered in advanced sarcomas, however, this approach is associated with toxicity.

Precision medicine promises better healthcare delivery by improving clinical practice. Using evidence-based substratification of patients, the objective is to achieve better prognosis, diagnosis, and treatment that will transform existing clinical pathways toward optimizing care for the specific needs of each patient. The wealth of today's healthcare data, often characterized as big data, provides invaluable resources toward new knowledge discovery that has the potential to advance precision medicine. The latter requires interdisciplinary efforts that will capitalize the information, know-how, and medical data of newly formed groups fusing different backgrounds and expertise. The objective of this paper is to provide insights with respect to the state-of-the-art research in precision medicine. More specifically, our goal is to highlight the fundamental challenges in emerging fields of radiomics and radiogenomics by reviewing the case studies of Cancer and Alzheimer's disease, describe the computational challenges from a big data analytics perspective, and discuss standardization and open data initiatives that will facilitate the adoption of precision medicine methods and practices. 23 5 2063 2079

Paraneoplastic arthritides are a group of inflammatory rheumatic syndromes induced by an occult and manifest malignancy, characterized by a wide range of musculoskeletal signs and symptoms that masquerade other rheumatic diseases such as rheumatoid arthritis. Although the pathogenesis of paraneoplastic arthritides is unknown, immune-mediated mechanisms can induce a paraneoplastic syndrome, with a dominant feature the polyarthritis. Common entities of paraneoplastic arthritides include paraneoplastic polyarthritis, hypertrophic osteoarthropathy, remitting seronegative symmetrical synovitis with pitting edema, palmar fasciitis and polyarthritis, and polyarthritis and panniculitis associated with pancreatic carcinoma. The electronic databases PubMed and Scopus were scrutinized using the following terms: paraneoplastic arthritis, paraneoplastic polyarthritis, or paraneoplastic rheumatic diseases. Abstracts, full articles, and selected references were reviewed. The aim of the present narrative review article was to describe the clinical characteristics, diagnostic evaluation, and management of paraneoplastic arthritides, and highlight the challenges that health care providers may encounter, distinguishing those conditions from other autoimmune rheumatic disorders. Future studies are needed to give insight into the mechanisms associated with paraneoplastic arthritides, leading to the development of novel diagnostic biomarkers.

Improved understanding of the immune system and its role in cancer development and progression has led to impressive advances in the field of cancer immunotherapy over the last decade. Whilst the field is rapidly evolving and the list of drugs receiving regulatory approval for the treatment of various cancers is fast growing, the group of PD1- PDL-1 inhibitors is establishing a leading role amongst immunomodulatory agents. PD1- PDL-1 inhibitors act against pathways involved in adaptive immune suppression resulting in immune checkpoint blockade. Within the last four years two PD-1 and three PD-L1 inhibitors have been utilized in clinical practice against a variety of malignancies. Focus was initially placed on targeting cancers considered immunogenic such as melanoma, renal and lung cancers but subsequently the application expanded to include amongst others Hodgkin Lymphoma, urothelial as well as head and neck cancer. This article provides a comprehensive review of the early and late phase trials that led to the regulatory approval of all five PD1- PDL-1 inhibitors in the corresponding cancer types. It presents available data on the combinations of PD1- PDL-1 inhibitors with other therapies (immunotherapy, targeted therapy and chemotherapy), the toxicity profile of the PD1- PDL-1 inhibitors and ongoing trials testing the efficacy of these agents in cancer types beyond those that have been addressed already. Finally, current and future challenges in the application of PD-1 and PD-L1 inhibitors are discussed with emphasis on the role of predictive biomarkers. 194 84 106

There is paucity of randomized controlled data on the role of systemic therapy in retroperitoneal sarcomas. The type of systemic therapy used is guided by the histological subtype. The majority of retroperitoneal sarcomas comprising liposarcomas and leiomyosarcomas are by and large chemotherapy insensitive. There is an urgent need for more efficacious systemic therapies in the management of early and advanced stage retroperitoneal sarcomas. 117 1 87 92

Cervical cancer is the fourth most frequently occurring cancer in women around the world and can affect them during their reproductive years. Since the development of the Papanicolaou (Pap) test, screening has been essential in identifying cervical cancer at a treatable stage. With the identification of the human papillomavirus (HPV) as the causative agent of essentially all cervical cancer cases, HPV molecular screening tests and HPV vaccines for primary prevention against the virus have been developed. Accordingly, comparative studies were designed to assess the performance of cervical cancer screening methods in order to devise the best screening strategy possible. This review critically assesses the current cervical cancer screening methods as well as the implementation of HPV vaccination in Europe. The most recent European Guidelines and recommendations for organized population-based programs with HPV testing as the primary screening method are also presented. Lastly, the current landscape of cervical cancer screening programs is assessed for both European Union member states and some associated countries, in regard to the transition towards population-based screening programs with primary HPV testing.

Background/Aim: Complete resection, surgical expertise and individualization of patient management in comprehensive oncology centres result in better clinical outcomes in patients presenting with retroperitoneal sarcomas. Patients and Methods: Clinical outcomes of primary and recurrent retroperitoneal sarcoma resections performed between January 2002 and December 2016 in two large surgical oncology, but non-sarcoma specialist centers, were reviewed to determine the efficacy of complete surgical resection as the principle instrument for treatment. The histological type, tumor size and grade, as well as organ resection, were recorded and subsequently reviewed. Results: Our study included 108 cases of sarcoma resection (60 firsttime, 38 second-time and 10 third-time laparotomies) in 60 patients (35 males and 25 females). Most patients had complete resection: 57 had a macroscopically complete (R0/R1) resection and three had R2 resection. The 90-day mortality rate was zero and morbidity was minimal. Fiveand 10-year overall survival (OS) rates were 88% and 79%, respectively, whereas the corresponding disease-free survival (DFS) rates were 65% and 59%, respectively. High-grade tumors were associated with decreased DFS (hazard ratio(HR)=3.35; 95% confidence interval(CI)=1.23-9.10; p=0.018) and decreased OS (HR=7.18; 95% CI=1.50-34.22; p=0.013). Conclusion: Complete surgical resection of retroperitoneal sarcomas combined with individualized patient management when offered by experienced surgical oncology teams, adhering to international guidelines, can succeed in providing patients with good long-term outcomes, comparable to those achieved at sarcoma-specialist centers. 37 4 2025 2031

Contains fulltext : 177634.pdf (Publisher’s version ) (Open Access) Gastrointestinal stromal tumors (GISTs) are composed of various molecular subtypes, with differing prognostic and predictive relevance. Previously, tumors lacking mutations in the KIT and PDGFRA genes have been designated as 'wild-type' GISTs; however, they represent a heterogeneous group currently undergoing further subclassification. Primary and secondary resistance to imatinib poses a significant clinical challenge, therefore ongoing research is trying to evaluate mechanisms to overcome resistance. Thorough understanding of the prognostic and predictive relevance of different genetic subtypes of GIST can guide clinical decision-making both in the adjuvant and the metastatic setting. Further work is required to identify tailored therapies for specific subgroups of GISTs wild-type for KIT and PDGFRA mutations and to identify predictive factors of resistance to currently approved systemic therapies.

For decades, doxorubicin alone or in combination with ifosfamide has been used in advanced soft tissue sarcoma (STS). In 2014, a comparison of doxorubicin alone versus the combination with ifosfamide (in the randomised phase III EORTC 62012) showed no difference in overall survival (OS), but a difference in response and progression-free survival (PFS) were observed in favour of the combination but at the expense of increased toxicity. Newer fosfamides, with slightly different modes of action, and potentially less toxicity, namely evofosfamide and palifosfamide have recently been tested in randomised phase III clinical trials in STS. The TH CR-406/SARC021 (June 2017) and the PICASSO III (September 2016) studies compared doxorubicin, as the standard arm, to doxorubicin in combination with evofosfamide and palifosfamide, respectively. In both studies, the combination arm produced increased response rates but at the expense of higher toxicity. However, there was no difference in OS or PFS in favour of the combination. Importantly, the median OS of patients receiving standard of care, doxorubicin, in both studies appeared improved from 12.8 months (95.5% CI 10.5–14·III) in the EORTC 62012 to 16.9 months (95% CI 14.8 to 22.9) in PICASSO III and 19.0 months (95% CI 16.2–22.4) in TH CR-406/SARC021. The results of these three randomised phase III studies highlight several critical issues related to the design and conduct of such trials in STS. We discuss these issues aiming to contribute to the ongoing debate about the optimal approach to perform clinical research in STS. © 2017 The Authors 84 257 261

Contains fulltext : 177453.pdf (Publisher’s version ) (Open Access) Primary and secondary resistance to currently available licensed tyrosine kinase inhibitors poses a real clinical challenge in the management of advanced gastrointestinal stromal tumors. Within the frame of early phase clinical trials novel systemic treatments are currently being evaluated to target both the well explored and novel emerging downstream effectors of KIT and PDGFRA signaling. Alternative therapeutic approaches also include exploring novel inhibitors of the KIT/PDGFRA receptors, immune checkpoint and cyclin-dependent kinase inhibitors. The final clinical trial outcome data for these agents are highly anticipated. Integration of new diagnostic techniques into routine clinical practice can potentially guide tailored delivery of agents in the treatment of a highly polyclonal, heterogeneous disease such as heavily pretreated advanced gastrointestinal stromal tumor.

BACKGROUND: Recent UK clinical guidance advises against continuing trastuzumab (T) beyond disease progression (PD) in the absence of brain metastases in patients with HER-2 positive (+ ve) advanced breast cancer. We have retrospectively evaluated the outcome of patients with HER-2 + ve locally advanced (LA) or metastatic breast cancer (MBC) who continued T beyond PD, treated in our unit. METHODS: All HER-2+ ve patients on our prospectively maintained database with LA or MBC who received T beyond PD after adjuvant or one line of T for advanced disease were assessed for response and outcome. From the timepoint of T continuation beyond PD, we calculated the overall disease control rate, time to progression (TTP), and overall survival (OS). RESULTS: One hundred and fourteen patients with HER-2 + ve LA or MBC treated with T beyond PD were identified. The main site of disease was visceral in 84 (74%) patients. Seventy-six (66%) had one line of chemotherapy before continuation of T beyond PD and 21 (19%) had two or more. Post-progression, 66 (58%) received T combined with chemotherapy. Of the 93 (82%) patients with documented clinical or radiological response evaluation, 67 (59%) were considered as having stable disease or better. The median TTP was 24 weeks (95% CI: 21-28) and the median OS was 19 months (95% CI: 12-24). CONCLUSION: Our results from an unselected group of patients provide additional evidence that continuation of T beyond PD is of clinical benefit. © 2011 Cancer Research UK. 104 11 1675 1679

Background: Despite the increasing use of positron emission tomography/computed tomography (PET/CT) in the management of patients with breast cancer, its role is yet to be defined. Patients and methods: We reviewed PET/CT scans carried out in breast cancer patients, the indication, concordance/discordance with other imaging and whether their use had altered patient management. Results: PET/CT scans (233) were carried out in 122 patients between July 2004 and October 2008. Indications were as follows: staging (S) (91), response assessment (RA) (87), clarification (C) of findings on other imaging (32) and reassurance (ASS) (23). In the S group, positive scans were helpful in accurately defining the extent of disease and guided localised or systemic treatment. PET/CT was particularly useful for detecting lytic bone metastases. One-third of the scans was carried out for RA. PET/CT allowed early RA and in some cases appropriate discontinuation of ineffective treatment. PET/CT was used effectively for the clarification of indeterminate lesions on CT (18), magnetic resonance imaging (15) and bone scan (13). In the ASS group, all scans were negative. Conclusions: PET/CT is useful in accurately staging metastatic disease, assessing response to systemic treatment and clarifying equivocation on other imaging. Incorporation of PET/CT in these areas contributes to breast cancer management optimisation. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. 22 2 307 314

Background. Aggressive fibromatosis (AF) is a locally invasive proliferative disease. The mainstay of treatment is surgery. Chemotherapy may be considered in inoperable AF following failure of hormonal therapy and/or NSAIDs. Material and methods. We conducted a retrospective search of the prospectively maintained Royal Marsden Hospital Sarcoma Unit database to identify patients with AF treated with chemotherapy between 1987 and 2009. Results. Thirty-nine patients, thirty one females and eight males, received one or more lines of chemotherapy. The most frequently employed chemotherapy regimens were methotrexate/vinblastine [MTX/VBL] (18) and pegylated liposomal doxorubicin [PLD] (14). MTX/VBL was administered weekly or every two weeks at MTX 50 mg and VBL 10 mg. Treatment duration ranged from three weeks to one year with a median of 4.5 months. Partial response (PR) was observed in 11% of cases, disease stabilisation (SD) in 60% and progressive disease (PD) in 22%. Time to progression ranged from one month to sixteen years. The main toxicities reported were mucositis (4), peripheral neuropathy (3), vomiting (3), and neutropenia (3). PLD was administered at 40-50 mg/m2 every four weeks, for up to six cycles. PR was achieved in 33% and in the remainder the disease was stable with no progression during treatment. Three (25%) patients have so far progressed after treatment. Symptomatic benefit, especially pain relief, was reported in 86% (12/14) of cases. Main toxicities included palmar plantar erythema (5) and mucositis (4). Discussion. MTX/VBL remains a useful combination but PLD is emerging as a well tolerated and effective systemic therapy in advanced AF. © 2011 Informa Healthcare. 50 3 455 461

Seminomas constitute more than half of testicular germ-cell tumours and 70-80% of patients with seminoma present with clinical stage I disease. Post-orchiectomy, management options include irradiation, surveillance or chemotherapy. Adjuvant irradiation to the infradiaphragmatic lymph nodes is the standard of care with relapse rates of 3-4%. Long-term follow-up data have shown association with late complications (cardiotoxicity, second malignancy, fertility impairment). Surveillance is an attractive alternative but relapse rates are higher ranging between 15 and 20%. Single agent carboplatin chemotherapy has demonstrated survival data equivalent to radiotherapy but long-term relapse and toxicity data are yet to be confirmed. Routine follow-up after irradiation and the role of risk stratification also remain unclear. Highly curative rates can be attained by all three modalities. Standard treatment with radiotherapy is challenged by surveillance and chemotherapy. Toxicity issues and patients' preferences are considered when management decisions are made. © 2008 Elsevier Ireland Ltd. All rights reserved. 71 1 22 28

Testicular germ cell tumors represent the most common malignancies in young males between the ages of 15 and 35; 50% of those with non-seminomatous germ cell tumors (NSGCT) have clinical stage I at diagnosis. Predictors for relapse include lymphovascular invasion, percentage of embryonal-cell carcinoma component, absence of yolk-sack histology and MIB1 proliferation rate. Therapeutic options following orchidectomy in stage I NSGCT comprise nerve-sparing retroperitoneal lymph node dissection (RPLND), surveillance or adjuvant cisplatin-based chemotherapy. Using a risk adapted approach, in about 50% of patients with clinical stage I NSGCT surveillance is favored in patients with good compliance. Adjuvant chemotherapy is recommended for patients at high risk for developing metastatic disease. Non-seminomatous germ cell testicular cancer is a curable neoplasia. All available treatment modalities produce excellent results, with a long-term survival of almost 100%. Consequently, therapy-induced toxicity is an important concern in the management of these patients. An individually tailored approach that takes into account the prognostic factor profile, as well as the patients' preferences and their ability to comply with treatment, is the key for the successful management of stage I testicular cancer. © 2008. 70 2 114 123

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Contains fulltext : 170961.pdf (Publisher’s version ) (Open Access) Soft-tissue sarcomas (STS) are a heterogeneous group of rare solid tumors of mesenchymal origin. This paper reviews the current status of systemic treatment in advanced and metastatic soft tissue sarcomas, with an emphasis on trabectedin. Trabectedin is a unique type of chemotherapeutic agent with multiple potential mechanisms of action. We discuss the putative mechanisms, as well as the toxicity and administration schedules of trabectedin, followed by its efficacy in first-line systemic therapy and beyond first-line systemic therapy.

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2568Background: Diarrhea is a common toxicity related to cancer treatment. Diarrhea occurs at different degrees of severity both within and outside the dose limiting toxicity window, influencing the dose and schedule of novel anticancer drugs. We aimed to assess the incidence, severity and factors predisposing to diarrhea in patients (pts) enrolled in phase I studies. Methods: This is a retrospective study of 1002 separate phase I trial pt-cases treated at the Royal Marsden Hospital Drug Development Unit between January 2010 and December 2014. Data were collected from our electronic records for consecutive pts participating in 80 different phase I trials. Results: The incidence of diarrhea was 32.1%. Grade 1-5 diarrhea was reported in 21.9%, 6.3%, 3.1%, 0.1% and 0.1% pt-cases respectively. 69.5% episodes of diarrhea were reported as drug related. 5.6% of pts had a specific trial intervention due to diarrhea such as dose interruption or withdrawal from study. Time on study was not significantly different i...

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Objectives Treatment options for metastatic soft-tissue sarcomas are limited. The aim of this study was to investigate the clinical activity of ifosfamide rechallenge in synovial sarcoma (SS), liposarcoma (LPS), leiomyosarcoma (LMS), and high-grade sarcomas not otherwise specified. Methods A retrospective search of the Royal Marsden Sarcoma Unit Database was performed to identify patients initially treated with ifosfamide (as single agent or in combination) and who were subsequently rechallenged with single-agent ifosfamide. Baseline demographics and response assessment were retrospectively obtained. Results Sixty-seven patients were identified and the median age at diagnosis was 41 years (range, 18 to 71 y). There were 29 cases of SS, 17 of LPS, 12 of LMS, and 9 of sarcomas not otherwise specified. First-line ifosfamide-containing therapy was given to 14 patients as adjuvant therapy (adjuvant group) and 53 patients as palliative therapy (palliative group). Clinical activity (partial response or stable disease) with single-agent ifosfamide rechallenge was documented in 50.0% of patients in the adjuvant group (7 in the second line) and 34.0% of patients in the palliative group (15 in the second line, 1 in third line, and 2 in the fourth line). The median progression-free survival in patients with documented clinical activity was 11.5 months (95% CI, 8.8-12.3) and 6.9 months (95% CI, 5.1-9.0), respectively, in the adjuvant and palliative group. Ifosfamide rechallenge was mostly active in SS patients (49.3%, 14 out of 29 patients with partial remission or stable disease). Conclusions Ifosfamide rechallenge has clinical activity in soft-tissue sarcoma and can be considered a viable option in treating metastatic disease.

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Treatment options for patients with metastatic synovial sarcoma are limited. Over recent years, trabectedin has emerged as an effective agent for patients with advanced soft tissue sarcomas resistant to anthracyclines and ifosfamide. The aim of this retrospective analysis was to study the efficacy of trabectedin in the subgroup of synovial sarcomas. A retrospective analysis was carried out on patients with advanced synovial sarcoma treated with trabectedin at four European reference sarcoma centers and within the Italian Rare Cancer Network between 2000 and 2013. Radiological response, progression-free, and overall survival, as well as serious and unexpected adverse events were retrospectively assessed. Sixty-one patients with metastatic synovial sarcoma were identified. The median number of previous chemotherapy regimens was 2 (range 1-6). Nine patients had a partial response, in addition to two minor responses, and 19 patients had stable disease, for an overall response rate of 15% and a tumor control rate of 50%. The median progression-free survival was 3 months, with 23% of patients free from progression at 6 months. The median progression-free survival in responding patients was 7 months. Trabectedin is a therapeutic option for palliative treatment of a subset of patients with metastatic synovial sarcoma. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. 26 6 678 681

Sarcomas are rare and heterogeneous mesenchymal tumors affecting connective tissue. For many years, doxorubicin-based chemotherapy has been the main systemic therapy option for patients with metastatic soft tissue sarcoma. This 'one size fits all' approach has led to marginal benefit, but the introduction of tyrosine kinase inhibitors in gastrointestinal stromal tumors has shown that sub-type-specific, molecularly targeted therapy can lead to significant advances. Next generation sequencing has led to the discovery of the biologic nature of many histological sub-types of sarcomas, and now an emphasis has been placed on assessment of novel therapies for each sub-group. However, the transition into the clinic is both challenging and protracted due to the rarity and heterogeneity of these tumors. The high failure rate of phase III trials in oncology has shown that clinical trials can be difficult to run, especially in rare forms of cancer like sarcomas. In this review, the authors provide an evaluation of the potential approaches toward better clinical trial design in sarcoma studies. © 2015 Informa Healthcare USA, Inc. 32 2 72 75

Collision tumors are rare neoplasms displaying two distinct cell populations developing in juxtaposition to one another without areas of intermingling. They are rare entities with only 63 cases described in English literature. Tumors encountered are gastric adenocarcinomas colliding with lymphomas, gastrointestinal stromal tumors, squamous cell carcinomas, and neuroendocrine tumors. Their cell origin is obsolete by the time of diagnosis. Different tumorigenesis theories have been suggested to explain their behavior, yet none has managed to provide satisfactory explanation for all cases. Clinically they are indistinguishable from the dominant tumor. Lack of data does not allow detailed assessment of their behavior yet they seem aggressive neoplasms with dismal prognosis. The majority of cases have been diagnosed postoperatively during histologic examination of specimens. There are no guidelines or concrete evidence to support best way of adjuvant or other types of treatment. However, these rare neoplasms might help in unlocking secrets of cancer behavior including tumorigenesis, differentiation, and adhesion and thus clinicians should be aware of their existence. © 2015 Adamantios Michalinos et al. 2015

Liposarcomas are one of the largest soft tissue sarcoma subgroups in adults, accounting for approximately 15%–20% of all soft tissue sarcomas. As described by Manji and Schwartz, they constitute a heterogeneous group of tumors with clinically distinct presentations, response to therapy, and prognosis. The commonest type, well-differentiated liposarcoma/ dedifferentiated liposarcoma, is characterized by a chromosomal amplification in 12q13-15, resulting in MDM2 and CDK4 overexpression. Myxoid liposarcoma has a translocation, t(12;16)(q13;p11), in greater than 90% of cases. Alterations in the PI3 kinase/AKT pathway have also been described, including mutations in PIK3CA, which are more common in round-cell tumors, and loss of the tumor suppressor gene PTEN. Activation of this pathway is demonstrated by phosphorylation of 4EBP1 and S6 downstream of mTOR. Pleomorphic liposarcoma is a subtype with a complex genetic profile and no uniformly expressed molecular alterations. The only curative option for soft tissue sarcomas is surgical excision with clear margins, and the quality of resection is an important prognostic factor for survival, especially in retroperitoneal liposarcoma. Therapeutic options are limited for patients with unresectable or metastatic disease. Chemotherapy comprising doxorubicin alone or in combination with other agents is associated with a low objective response rate withno survival benefit inwell-differentiated liposarcoma/dedifferentiated liposarcoma, whereas median survival for metastatic myxoid liposarcoma, the most chemosensitive subtype, remains limited.

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Background. Soft-tissue sarcomas (STS) are a heterogeneous group of diseases with lack of effective treatments in most cases. Previous data suggest that continuous infusional ifosfamide regimens might improve cytotoxicity and tolerability compared to standard schedules. Methods. We retrospectively report the outcome of 35 patients affected by STS treated with a 14-day infusional ifosfamide regimen (1000 mg/m2/day) in our institution. Predictive factors for toxicity were also explored. Results. Median age was 53 years. There were 16 males and 19 females. Classification by histology was dedifferentiated liposarcoma (DDLPS): 22 (62.8%), synovial sarcoma: 7 (20%), myxoid/round-cell liposarcoma: 3 (8.5%), and others: 3 (8.5%). Overall, 7 patients (20%) achieved partial response (PR) and 10 patients (29%) achieved stable disease (SD). DDLPS showed special sensitivity: 5 patients (22.7%) had PR, 7 patients (31.8%) had SD, and disease control rate was 54.5%. Median progression-free survival and overall survival were 4.2 and 11.2 months, respectively. The most common toxicities were fatigue, nausea, and vomiting (all grades: 85.7%, 83%, and 54.3%, resp.). Neither hypoalbuminaemia nor gender was found to predict toxicity, although encephalopathy predominantly affected females. Conclusion. Ifosfamide administered as a 14-day continuous infusion is a safe regimen in STS with notable activity in DDLPS. © 2013 Juan Martin-Liberal et al. 2013

Approximately 50% of patients with localized soft tissue sarcomas will develop recurrent disease after complete surgical resection, requiring alternative means of treatment. Conventional chemotherapy comprising of doxorubicin and ifosfamide has shown benefit in advanced disease, however, there remains a clear need for more effective, less toxic, therapies for the treatment of this heterogeneous group of mesenchymal malignancies. Recently, greater emphasis has been placed on the underlying biology of individual sarcoma subtypes, with the development and evaluation of novel therapies both in common and in rare subtypes. In addition, there is a greater specificity in the selection of chemotherapy agents based on activity in individual histological subtypes. Despite these advances the management of sarcoma, and in particular of rare subtypes, remains a major challenge. Some histological subtypes are resistant to conventional chemotherapy and patients with these diseases should be offered participation in early phase clinical trials of novel drugs. © 2013 Expert Reviews Ltd. 13 2 211 223

PURPOSE OF REVIEW: The purpose of this review is to present the most recent advances in the diagnosis of the more common leiomyosarcoma (LMS) anatomic variants, potentially useful prognostic markers that have recently been identified and the systemic approaches currently used or under evaluation to improve the outcome of patients with this disease. RECENT FINDINGS: Over the last few years emphasis has been placed on incorporating effective imaging tools and using pathological biomarkers in the diagnostic workup of LMS. Moreover, efforts are being made to identify meaningful prognostic and predictive parameters that will aid the development of effective novel therapeutics. The number of systemic therapies available to treat LMS has increased over the last decade, but the selection of systemic therapy is not based on the anatomic origin of LMS. SUMMARY: Currently, the only curative option in LMS is surgery and despite progress in systemic therapy the outcome of patients with advanced/metastatic disease remains poor. Better understanding of the underlying biology of the LMS variants, improved diagnostics and more effective, less toxic therapeutic agents are required. Copyright © Lippincott Williams & Wilkins. 25 4 384 389

11579Background: Emerging targeted and combination treatments of novel anticancer drugs in the molecular era mandate an increasing number of paired fresh tumour biopsies. We aimed to assess risks a...

The impact of adding bevacizumab to perioperative chemotherapy in patients with colorectal cancer (CRC) undergoing liver resection is yet to be defined. A retrospective review of our patient records showed that the addition of bevacizumab did not increase morbidity or mortality related to liver resection. Pathologic complete response (CR) is associated with prolonged survival. Background: Patients with colorectal cancer (CRC) and liver metastases benefit from perioperative chemotherapy and liver resection. The potential benefit of adding bevacizumab is yet to be defined. The impact of bevacizumab on liver resection complications has been explored in a small number of retrospective studies. Methods: The records of patients with CRC and liver metastases who underwent liver resection and had received perioperative chemotherapy were reviewed. Complications were reported separately for 2 groups (chemotherapy alone vs chemotherapy and bevacizumab). Survival outcomes (progression-free survival [PFS] and overall survival [OS]) for responders and nonresponders were estimated using the Kaplan-Meier method. Results: Fifty-two patients received chemotherapy alone and 42 patients received chemotherapy and bevacizumab. The median time from the end of systemic treatment to liver resection was 59 days (33-181 days) for the chemotherapy group and 62 days (44-127 days) for the chemotherapy and bevacizumab group. Postoperative complications developed in 54% of the chemotherapy group and in 48% of the chemotherapy and bevacizumab group. Severe complications (grade III-V) occurred in only 13% and 12%, respectively (P .822). Pathologic complete response (CR) was seen in 11/94 patients. Poor performance status (PS) before starting chemotherapy was associated with higher rates of complications (P .002), and severe complications led to prolonged hospital admission (P .001). Patients with pathologic CR had longer OS (P .0275), but there was no difference in OS between responders and nonresponders (P .778). Conclusion: The addition of bevacizumab to chemotherapy does not increase liver resection complication rates. Pathologic CR is associated with prolonged survival.

Over the past 120 years, the discipline of oncology has evolved so that a multitude of anatomical and increasingly complex functional imaging techniques are now applicable in both clinical and research platforms. This Timeline article revisits the achievements of the pioneer techniques in cancer imaging, discusses how these techniques have changed over time, provides some examples of clinical importance, and ventures to explain how imaging will remodel the future of modern oncology. © 2012 Macmillan Publishers Limited. 9 12 728 737

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To the Editor,Solitary fibrous tumour (SFT) is a rare mesenchymal tumour that arises from serosal surfaces, predominantly the pleura but also from extrapleural locations, such as the extremities, h...

Background: Epithelioid sarcoma is a rare soft tissue sarcoma subtype. The response of this disease to chemotherapy is not well described. The aim of this study was to investigate the response rate and progression-free survival in a series of epithelioid sarcoma patients treated with chemotherapy at a single referral center. Methods: A retrospective search of a prospectively maintained database was made to identify epithelioid sarcoma patients treated with chemotherapy between 1990 and 2009. Radiological response and histological diagnosis were re-reviewed for this study. Results: Twenty-one epithelioid sarcoma patients treated with chemotherapy were identified; follow-up data on palliative chemotherapy was available on 20 of these patients. The median age was 36.5 years (range, 17.4 to 64.8 y) and the male/female ratio was 19:2. Ten patients (50%) were treated with single-agent anthracycline, 9 patients (45%) were treated with a combination therapy (anthracycline and ifosfamide), and 1 patient received trabectedin (5%). Three patients achieved a partial response, 12 had stable disease, and 5 progressed. The median progression-free survival was 29 weeks (95% confidence interval [CI]: 23-35). Seven and 3 patients received second-line and third-line palliative chemotherapy, respectively. The median overall survival from commencing palliative chemotherapy in our series was 51 weeks (95% confidence interval; 29-73). Conclusions: Systemic chemotherapy provides satisfactory palliation in patients with epithelioid sarcoma. However, this is an aggressive disease, responses to chemotherapy are of short duration and there is a need for more effective novel therapies in the treatment of this condition. Copyright © 2012 by Lippincott Williams & Wilkins. 35 4 351 357

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Summary: Trastuzumab in combination with chemotherapy is now standard of care for patients with early HER2-positive cancers larger than 1 cm. Some patients however may not need or simply may not want chemotherapy with its associated toxicities. For example patients with small (

Advances in the systemic treatment of early breast cancer have led to significant improvements in survival for patients with hormone receptor- and/or HER2-positive disease. In recent years, interest has focused on tumors that lack expression of the estrogen receptor, progesterone receptor and HER2, the so-called triple-negative subgroup. As a group, triple-negative cancers have a relatively aggressive clinical course, with early development of visceral metastases and a poor long-term prognosis. These tumors, however, encompass a wide range of subtypes with varying prognosis, including a number of special types with a good prognosis (e.g., adenoid cystic carcinomas and secretory carcinoma). There is considerable overlap between triple-negative and basal-like tumors; however, microarray studies have demonstrated that the overlap between basal-like and triple-negative cancers is not complete. The similarities between sporadic triple-negative cancers and tumors arising in BRCA1 mutation carriers and the fact that the majority of BRCA1 tumors display a triple-negative phenotype have led to studies demonstrating a potential loss of BRCA1 function in triple-negative cancers and offered potential therapeutic avenues for patients with these cancers. However, it should be noted that triple-negative breast cancers comprise a heterogeneous group of tumors. Understanding the molecular underpinning of distinct subgroups of these cancers is crucial for the identification of novel therapeutic targets and individualization of treatment for patients with triple-negative disease. © 2010 Expert Reviews Ltd. 10 8 1197 1213

Clear cell sarcoma is a rare translocation-related sarcoma. There have been few studies documenting the response rate and progression-free survival in clear cell sarcoma patients treated with palliative chemotherapy. The prospectively maintained databases of two referral centres were searched to identify clear cell sarcoma patients treated with chemotherapy. Twenty-four patients were treated with palliative first-line chemotherapy with a median age of 30 years at diagnosis. There were 18 men and 6 women. One (4%) achieved a partial response and 9 (38%) had stable disease. Fourteen patients (58%) progressed on therapy. The median progression-free survival was 11 weeks (95% CI, 3-20 weeks). The median overall survival from commencing first-line chemotherapy was 39 weeks (95% CI, 34-45 weeks). Second-line chemotherapy was administered to 12 patients, 11 (92%) of these progressed and one (8%) had stable disease. Of the 5 patients treated with third-line chemotherapy, 4 (80%) progressed and one (20%) had stable disease. One patient received fourth-line chemotherapy and maintained stable disease for 4 months. Conventional chemotherapy has minimal activity in clear cell sarcoma as documented by the response rate of 4% and median progression-free survival of 11 weeks in this retrospective series. These data provide a reference for response and outcome in the assessment of novel agents in this histological subtype. © 2010 Springer Science+Business Media, LLC. 28 3 859 863

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Background: Aggressive fibromatosis (AF) or desmoid tumour is a monoclonal proliferation which is locally invasive but does not metastasize. If local treatment fails to control the disease, systemic treatment with anti-oestrogens, non-steroidal anti-inflammatory drugs (NSAIDs) or chemotherapy can be used. Recent reports indicate that pegylated liposomal doxorubicin (PLD) is effective. Methods: Twelve patients with AF received PLD between February 2006 and May 2009. PLD was administered intravenously (iv) at 50 mg/m2 over 1 h every 4 weeks. Results: The female/male ratio was 11:1 and median age at presentation was 29 years (range 3-53). Objective response (PR) was achieved in 4 (36%) of 11 patients. In one case ongoing shrinkage of the tumour was observed for over 12 months and partial remission was achieved at 14 months after the completion of treatment. Seven patients achieved stable disease. One patient is currently undergoing chemotherapy. Clinical benefit in terms of pain relief, improved mobility or cosmesis was observed in 11 patients. Nine patients (75%) had no evidence of progression at the end of this follow-up period and disease control has ranged from 7 to 39 months with a median of 14 months. The most severe toxicities observed were palmar-plantar erythema (4) and mucositis (3). In 6 cases (55%) toxicity resulted in dose reduction. Conclusion: This is the largest series of patients with AF receiving PLD reported to date. PLD as a single agent therapy has acceptable toxicity and highly promising activity in unresectable AF and may provide long-term clinical benefit in some patients. © 2009 Elsevier Ltd. All rights reserved. 45 17 2930 2934

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