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Background: Radiation induced angiosarcoma (RIAS) of the breast is a rare and aggressive complication of radiotherapy. Due to the rarity of this disease, much of the evidence for its management is based on case reports or small retrospective series. We sought to describe the management and outcomes of RIAS in a large single-institution series. Methods: All patients diagnosed with RIAS between January 2000 and January 2014 were identified from an institutional database. Results: A total of 49 patients were identified. Median age at diagnosis was 72 years (range 51-93). Median time from completion of radiotherapy to diagnosis of RIAS was 7.5 years. Median tumour size at presentation was 5.0 cm (1.5-19.0). The majority of patients presented with localised disease (47, 95.9%). Of these, 35 (74.5%) were suitable for surgery and underwent surgery with curative intent. Twelve patients presented with localised irresectable disease. Of these, 7 received systemic chemotherapy, with a sufficient response to facilitate surgery in 3 patients. Following potentially curative surgery, 2-year local recurrence-free was 55.2%. Survival was significantly prolonged in patients presenting with resectable disease (2-year overall survival 71.1% vs 33.3%, p < 0.001). Tumour size >5 cm was prognostic of distant metastases-free survival and overall survival. Conclusion: RIAS are rare, aggressive soft-tissue lesions with limited treatment options and high-rates of both local and systemic relapse. [ABSTRACT FROM AUTHOR]

Background: The efficacy and toxicity of first line palliative chemotherapy for soft tissue sarcomas (STS) in the elderly is poorly described., Methods: Patients over the age of 65 years receiving first line chemotherapy for advanced non-GIST STS January 1998 - January 2012 at the Royal Marsden Hospital were identified. Data regarding survival and predictive factors were collected retrospectively., Results: 120 patients (52 females) with a median age of 72 (range 65-83) were treated. The most common histological subtypes were undifferentiated sarcoma (30%), leiomyosarcoma (27%), angiosarcoma (14%). 42% of patients had high grade tumours. 70% of patients had metastatic disease at presentation; lung metastasis being the most common disease site (72%). 80% received single agent chemotherapy, mostly with doxorubicin (60%). The median number of cycles was 2 (IQR 3). A partial response was reported in 20% of patients with disease stabilisation in a further 20%. 38% of patients were hospitalised for chemotherapy related toxicity. The median overall survival (OS) was 6.5 months (95% CI 4.7-8.3). Anaemia, lymphopenia, hypoalbuminemia, sarcoma subtype and co-morbidities were predictive for overall survival., Conclusion: The overall survival for elderly patients with STS is poor but several predictive factors have been identified. Hospital admissions for chemotherapy related toxicity are common.

Background: Hormonal manipulation is sometimes recommended in the treatment of metastatic endometrial stromal sarcoma, but there are few data assessing the efficacy of endocrine therapies in this subtype of uterine sarcomas., Methods: We performed a retrospective electronic medical record review of patients with metastatic ESS treated with a hormonal agent at Royal Marsden Hospital between 1999 and 2011. We assessed progression-free survival (PFS), objective response and toxicity profile among patients with measurable disease., Results: Thirteen patients with metastatic ESS were treated with hormonal therapies. Hormone receptor status (estrogen and progesterone receptors) was assessed in 9 out of 13 patients and in all of them it was moderately to strongly positive. Aromatase inhibitors (AIs) were prescribed as first endocrine line in 11/13 patients and progestins in the remainder, while in 2(nd) line treatment AIs were prescribed in 7/10 patients, followed by progestins and GnRH analogues. Median PFS for 1(st)line was 4.0 years (95% CI: 2.4 - 5.5 years) with 5-year progression-free rate of 30.8% (95% CI: 5.7 - 55.9%), both of which reflect the indolent natural history of ESS. Best objective response was partial response (PR) in 6/13 patients (46.2%; 95% CI: 19.2 - 74.9) and clinical benefit rate (defined as complete response + PR + stable disease ≥6 months) was 92.4% (95% CI: 64.0 - 99.8%; 12/13 patients). Median PFS for 2(nd) line was 3.0 years (95% CI: 2.0 - 4.1 years) with 2-year progression-free rate of 88.9% (95% CI: 68.3 - 100.0)., Conclusions: In this cohort of metastatic ESS patients, 1st line endocrine treatment achieved objective response in 46.2% of them and clinical benefit in 92.4%. Tamoxifen and hormone replacement therapy should not be prescribed in patients with ESS due to their detrimental effects. Until more solid data are available, a reasonable recommendation would be that 1(st) line treatment with an endocrine treatment, preferably with an AI. Moreover, in view of the positive outcomes of our patients that received 2(nd)/3(rd)line endocrine treatments, all available hormonal options should be used in sequence in the management of ESS.

Background: Tyrosine kinase inhibitors (TKI) have revolutionized the treatment of gastrointestinal stromal tumors (GIST) although most patients develop resistance to first and second-line therapies. Regorafenib, an oral multi-targeted TKI, has demonstrated benefit in previously treated GIST patients., Methods: We assessed safety and activity of regorafenib in patients treated within the Managed Access Program (MAP). All consecutive patients with advanced GIST who had progressed on or were intolerant to imatinib and sunitinib were recruited from the Royal Marsden and University College Hospitals. We retrospectively reviewed the data for response, toxicity, treatment duration and survival. Response was assessed by RECIST and Choi criteria. Toxicity was graded according to CTCAE v4.0 criteria., Results: 20 patients were included in the MAP in the UK between 3/2013 and 9/2013. Median age was 68 (range 45-87), 65% of patients were male. Performance Status was 0-1 for 18 patients (90%), 2 for 2 patients (10%). The median treatment duration was 9.25 months (range 0.1-15.33). 18 patients were assessable for response and all patients attained a best response of at least stable disease. At a median follow-up of 12.6 months, there were 2 partial responses (11%) by RECIST and 7 partial responses (39%) according to Choi criteria. 7 patients remain on regorafenib. 3 patients discontinued treatment due to unacceptable adverse events; fistulation, myalgia and fatigue. 10 (50%) patients had grade 3 toxicities and 11 (55%) patients required a dose reduction. Median PFS was 9.4 months (95% Cl: 6.2-not calculable) and median OS was 12.2 months (95% Cl: 10.5-not calculable). Notably, prolonged stable disease was seen in 1 patient with exon 9 mutation and 1 patient with PDGFR D842V mutation., Conclusions: These data demonstrate encouraging activity and tolerability of regorafenib in routine clinical practice. The documented adverse events are in line with previous trial data.

Background: Aromatase inhibitors (AIs) have not been used consistently as part of the management of hormone receptor positive uterine leiomyosarcomas (ULMS). As a result, the published data regarding the efficacy of AIs in this subtype of ULMS are sparse., Methods: We performed a retrospective electronic medical record review of patients with ULMS treated with an AI, in the 1st or the 2nd line setting, at the Sarcoma Unit of the Royal Marsden Hospital between 2001 and 2012. We assessed progression-free survival (PFS), objective response and toxicities and explored the correlation of the intensity of the hormone receptor status, as well as of the grade with PFS., Results: Sixteen patients with measurable advanced ULMS were treated with an AI in our unit. All of them were oestrogen receptor (ER) and progesterone receptor (PgR) positive. Letrozole was used in all patients as 1st line endocrine therapy, while exemestane was mainly prescribed as 2nd line (83%). Median PFS in 1st line was 14 months (95% CI: 0 - 30 months), and prolonged PFS was more likely to be observed in patients with low grade compared to high grade ULMS (20 months vs. 11 months), and in moderately/strongly ER positive compared to weakly ER positive ULMS (20 months vs. 12 months). Best response was partial response (PR) in 2/16 patients (12.5%) and clinical benefit (CB), defined as complete response (CR) + PR + stable disease ≥6 months, was observed in 10/16 patients (CB rate (CBR) 62.5%). Median duration of 2nd line was 3 months and median PFS was not reached. The 1-year progression-free rate for the 2nd line AI was 80%. Best response was PR in one patient and CBR was 50%. AIs were well tolerated in both lines of treatment., Conclusions: In this population of patients with hormone positive ULMS, AIs achieved a significant CBR (62.5%) in 1st line, which was retained in 2nd line (CBR: 50%). The relatively prolonged median PFS (14 months), along with the favourable toxicity profile could place AIs among the first choices of systemic treatment in hormone positive ULMS, preferably in strongly positive (>90%), and/ or low grade and low volume disease.