Treatments and Outcomes in Oligometastatic Soft Tissue Soft Sarcoma - A Single Centre Retrospective Analysis.

BACKGROUND/AIM: Distinguishing true oligometastatic disease from early polymetastatic disease is vital in patients with soft tissue sarcoma as contemporary treatment strategies differ significantly. Clinical factors such as tumour biology, organ involved, number of lesions, and patient fitness influence clinical decisions. PATIENTS AND METHODS: A retrospective search of a prospective database identified patients with new distant relapse, treated between 2009 and 2012. RESULTS: A total of 223 patients were included, and oligometastases were diagnosed in 81 (36%) patients, which were pulmonary in just over half of cases. These were treated with local therapy in 66 of 89 cases, and 7 patients received subsequent treatment for additional oligometastases. Metastasectomy was the most common treatment modality. A total of 16/66 patients (24%) underwent active surveillance for >6 months prior to local therapy. CONCLUSION: Patients with oligometastatic disease can experience durable disease control with timely multimodality treatment approaches for evolving metastatic disease, where disease biology allows.

Metastatic Soft Tissue Sarcomas in Adolescents and Young Adults: A Specialist Center Experience.

Purpose: Soft tissue sarcomas (STS) account for 8% of all cancers in adolescents and young adults (AYAs). Metastatic STS contribute significantly to disease-related mortality in this age group; however, data are limited due to under-representation in clinical trials. Methods: AYAs aged 18-39 years, diagnosed with metastatic STS between 1990 and 2012, were identified from The Royal Marsden Hospital database. Outcomes of interest were clinical characteristics, treatment patterns, overall survival (OS), and prognostic factors. Results: Overall, 455 patients were included. Median age at diagnosis of metastatic STS was 33 years (interquartile range [IQR] 27-37 years). The most common histological subtypes were leiomyosarcoma (n = 68, 15%), synovial sarcoma (n = 68, 15%), Ewing sarcoma (n = 44, 10%), and rhabdomyosarcoma (n = 35, 8%). Treatments included systemic therapy (n = 395, 87%; median 2 lines [IQR 1-3]; clinical trial n = 93, 22%), radiotherapy (n = 297, 66%), and metastasectomy (n = 191, 43%). Median duration between last chemotherapy regimen and death was 4.6 months (IQR 2-10). Median OS was 19.2 months (95% confidence interval [CI] 15.8-22.2); 5-year OS was 16%. Of common subtypes, patients with rhabdomyosarcoma had the worst OS (8.8 months; 95% CI 7.9-11.4). Adverse prognostic factors included male gender, synchronous metastases, bone or liver metastases, first-line polychemotherapy, and no metastasectomy. Conclusions: Outcomes were variable; patients with supposed chemosensitive subtypes had particularly poor survival. The diverse behavior of STS in AYAs highlights the need for subtype-specific clinical trials.

Toxicity management of regorafenib in patients with gastro-intestinal stromal tumour (GIST) in a tertiary cancer centre.

BACKGROUND: Regorafenib is a multi-kinase inhibitor approved as third line treatment for metastatic GIST. Dose limiting toxicities are frequently seen and many patients require dose reductions. This study aimed to evaluate regorafenib toxicities and their management in a real-world GIST population. METHODS: Retrospective review of a prospectively maintained database identified 50 patients with GIST treated with regorafenib at our centre between March 2013 and September 2018. RESULTS: Median progression free survival (PFS) was 7.7 months [interquartile range (IQR) 2.8-14.4 months]. Median overall survival (OS) from start of regorafenib to death or last follow up was 15.7 months (IQR 9.2-28.4 months). Baseline median Eastern Cooperative Oncology Group (ECOG) performance status on starting regorafenib was 1. The main reason for discontinuing regorafenib was progressive disease (PD) (31/50 [62%]) rather than toxicity (10/50 [20%]). Grade 3-4 adverse events (AEs) were seen in 23/50 (46%) patients; palmar-plantar erythrodysesthesia (PPE) was most frequently seen (9/50 (18%)). Two patients died whilst on treatment with regorafenib from multi-organ failure secondary to sepsis (4%). Dose reductions were required in 19/50 patients (38%) and 8/50 (16%) patients started regorafenib at a lower dose band than the recommended dose (160 mg) due to comorbidities or concern over a higher individual risk of toxicity. CONCLUSION: Although PD was the main reason for discontinuing treatment, toxicity management and dosing of regorafenib remains critical. Median duration of treatment was longer compared to previous studies suggesting a durable clinical benefit with regorafenib with rigorous toxicity management.

Low-grade Fibromyxoid Sarcoma: Treatment Outcomes and Efficacy of Chemotherapy.

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma subtype with a generally indolent pattern of clinical behaviour, but treatments for advanced disease are limited. PATIENTS AND METHODS: A retrospective search of a prospectively maintained institutional database identified 102 patients treated from December 1994 to August 2018. We evaluated the outcome of patients and the efficacy and safety of non-surgical therapies in LGFMS. RESULTS: Ninety-four out of 102 (92.2%) underwent primary resection, seven (6.9%) were treated with systemic therapy and one (1.0%) is currently being treated with pre-operative radiotherapy. The RECIST 1.1 response rate to first-line chemotherapy was 0%, and median progression-free survival was 1.84 months (95% confidence intervaI=0.10-3.6 months). CONCLUSION: Conventional systemic therapy has limited efficacy in advanced LGFMS.

Outcome of Primary Desmoid Tumors at All Anatomic Locations Initially Managed with Active Surveillance.

BACKGROUND: The behavior of desmoid tumors is unpredictable and varies from spontaneous remission to symptomatic and radiologic progression. This study aimed to evaluate the radiologic and symptomatic course of the disease in patients initially managed with active surveillance. METHODS: Patients with a primary desmoid tumor at any anatomic location diagnosed between 1998 and 2016 were identified in a prospectively maintained database from a single sarcoma reference center in the United Kingdom. Inverse univariate Cox proportional hazard regression analyses were conducted to evaluate the course of the disease and indications for initiating treatment. RESULTS: The study identified 168 patients with a primary desmoid tumor initially managed with active surveillance. The tumors were located in the abdominal wall (n = 61, 36%), an extremity (n = 51, 30%), chest wall (n = 30, 18%), intra-abdominal site (n = 15, 9%), or elsewhere (n = 11, 6%). Of all the patients, 36% experienced radiologic progressive disease, 36% had stable disease, and 27% regressed. The patients younger than 50 years were more likely to progress (p = 0.046), whereas the patients with chest wall or upper-extremity tumors reported significantly more pain (p = 0.01). Eventually, 46% of the patients proceeded to treatment. The median time to start of treatment after initial surveillance was 31 months, whereas the median follow-up time for the patients not receiving any treatment was 40.5 months. The indications for initiation of treatment were pain (32%), progression (31%), or both (13%). CONCLUSIONS: Patients with desmoid tumors can be managed with initial active surveillance, although almost half of patients may eventually need treatment. Pain, tumor progression, or both are the most common indications for the initiation of treatment.

Gemcitabine Re-challenge in Metastatic Soft Tissue Sarcomas: A Therapeutic Option for Selected Patients.

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.

Poor treatment outcomes with palliative gemcitabine and docetaxel chemotherapy in advanced and metastatic synovial sarcoma.

The outcome for patients with unresectable or metastatic soft tissue sarcoma remains poor with few treatment options. Synovial sarcoma is a rare type of sarcoma, predominantly affecting adolescents and young adults. Following failure of first-line anthracycline-based chemotherapy, several salvage options are available. We reviewed the safety and efficacy of gemcitabine/docetaxel chemotherapy in two tertiary oncology centres. We identified patients treated with gemcitabine/docetaxel between 2004 and 2016 in a UK and a US oncology centre using retrospective pharmacy and medical records. Treatment response, toxicity and outcome data were collected. Twenty one patients were treated with gemcitabine/docetaxel, the majority as a second- or third-line treatment for metastatic disease. The response rate was 5% with a median progression-free survival of 2 months (95% CI 1.3-3.7). Toxicities reported were as expected for this chemotherapy combination. Treatment was not discontinued due to toxicity. Gemcitabine/docetaxel chemotherapy shows little efficacy in synovial sarcoma and should not be offered to this patient group outside a clinical trial context.

First line palliative chemotherapy in elderly patients with advanced soft tissue sarcoma.

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.

Systemic treatment options for epithelioid haemangioendothelioma: the Royal Marsden Hospital experience.

BACKGROUND: Epithelioid haemangioendothelioma (EHE) is a rare vascular tumour, which can arise at any site. There is little published data about the management of these tumours. PATIENTS AND METHODS: A retrospective review of patients with histologically-proven EHE presenting to the Royal Marsden Hospital from January 1999 to January 2012. RESULTS: Thirty-two patients (23 females) were identified with a median age of 44 (range=17-78). Twenty patients presented with diffuse disease. Median overall survival (OS) was 9.8 years in 10 patients with operable disease. Amongst those with inoperable disease (n=22), patients with liver disease had the longest median OS (9.8 years), while those with lung and mediastinal disease had the shortest OS (3.6 years). A variety of treatments were used for inoperable disease with infrequent radiological responses. CONCLUSION: The clinical behaviour can vary depending on the site of disease. Surgery, if feasible, has the best outcome. In those with inoperable disease, a period of observation to assess the tumour behaviour is recommended. The role of medical therapy remains unclear.

A retrospective study of patients with malignant PEComa receiving treatment with sirolimus or temsirolimus: the Royal Marsden Hospital experience.

UNLABELLED: Perivascular epithelioid cell tumors (PEComas) are rare tumors driven by tuberous sclerosis complex gene mutations causing up-regulation of mTOR. We report the outcome of ten consecutive patients treated with sirolimus or temsirolimus. PATIENTS AND METHODS: A retrospective analysis was performed on patients seen between 2007 and 2013. Demographic and treatment data were collected and radiological response was assessed. RESULTS: Ten patients were investigated, eight females, with median age of 47.5 years. Nine patients received sirolimus, one temsirolimus. The median treatment duration was 128 (range=7-1,366 days). Temsirolimus was given at 25 mg IV weekly and median starting dose of sirolimus was 3 mg daily. Seven patients were evaluable for response by RECIST: 5 showed partial response (50%), 1 stable disease (10%) and 1 progressive disease (10%). Two patients progressed rapidly on treatment. One patient stopped due to grade 3 hyperlipidaemia although CT scan shows maintained response. Three patients continue on treatment while the remainder stopped due to disease progression. CONCLUSION: Our study confirms that mTOR inhibition with sirolimus/temsirolimus is well-tolerated with good radiological responses, albeit short-lived, and supports its use in PEComas.

Angiosarcoma of the face and scalp: effective systemic treatment in the older patient.

BACKGROUND: Angiosarcoma of the face and scalp, though rare, frequently affects older people and the prognosis is poor. Due to its rarity, optimal management of advanced disease with chemotherapy has been difficult to define. OBJECTIVE: This is a retrospective review of patients treated at the Royal Marsden Hospital (RMH), looking at chemotherapy regimens, toxicity profile and treatment outcome in this elderly population over the last 20years. MATERIALS AND METHODS: Detailed clinical-pathologic data were collected on patients treated for head and neck angiosarcoma at RMH between 1992 and 2011. RESULTS: Thirteen patients (median age: 79years) were eligible for analysis. The majority (92.3%) received taxanes with a response rate of 83.3% and median progression-free survival (PFS) of 7months. Although the main toxicities were lethargy and peripheral neuropathy, a median number of 6 cycles of paclitaxel were administered. Doxorubicin was used in 57% of patients (median number of cycles: 3) with a response rate of 50% (median PFS: 3months). Cardiotoxicity occurred in 2 out of 7 cases and led to discontinuation of treatment. Overall, 57.1% of patients received chemotherapy at least 2 lines of chemotherapy. There were no deaths attributable to systemic treatment. CONCLUSIONS: Advanced angiosarcoma of face and scalp can be controlled with multiple lines of chemotherapy, consisting primarily of taxanes as well as anthracyclines. Old age should not preclude systemic therapy although safety and quality of life issues deserve careful consideration.

Clinical activity and tolerability of a 14-day infusional Ifosfamide schedule in soft-tissue sarcoma.

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/m(2)/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.

Desmoplastic small round cell tumour: characteristics and prognostic factors of 41 patients and review of the literature.

BACKGROUND: Desmoplastic small round cell tumour (DSRCT) is a rare but frequently fatal sarcoma, and many of its characteristics still require further clarification. METHODS: We retrospectively analysed 41 patients treated at or referred to two regional referral centres in the UK between 1991 and 2012. A review of the current literature was also performed. RESULTS: The median age of presentation was 27 years (range 16 to 45 years), with a male-to-female ratio of 3:1. Ninety percent of patients had disease in the abdomen. The median size of the presenting tumour was 13 cm (range 3.5 to 23 cm), and 80% had metastatic disease at diagnosis, mainly in the liver (33%) and lungs (21%). Time-to-progression (TTP) was 3.9, 2.3 and 1.1 months after first-, second- and third-line chemotherapy, respectively. First-line treatment with VIDE chemotherapy appeared to confer the longest TTP (median 14.6 months). Ifosfamide and doxorubicin resulted in TTP of >3.8 months when used in any-line setting. Eleven patients received targeted agents as part of a clinical trial. After a median follow-up of 14 months, the overall median survival (MS) was 16 months. There was no difference in MS with regards to age, gender, or size of the presenting tumour. Patients with extra-abdominal disease survived longer compared to those with tumours in the abdomen (all still alive vs MS of 15 months; P = 0.0246). Patients with non-metastatic intra-abdominal disease who underwent surgery had an MS of 47 months (16 months for those who did not have surgery; P = 0.0235). Radiotherapy for locoregional control in patients with metastatic intra-abdominal DSRCT was associated with longer survival (MS of 47 vs 14 months; P = 0.0147). CONCLUSIONS: DSRCT is a rare but often fatal disease that mainly affects younger male patients. Those with intra-abdominal DSRCT have a poorer prognosis, although surgical resection for localised disease and radiotherapy in the metastatic setting are associated with improved survival. A patient's age, gender and size of presenting tumour do not have prognostic significance.

Role of palliative chemotherapy in advanced epithelioid sarcoma.

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.

Chemotherapy in clear cell sarcoma.

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, 3­20 weeks). The median overall survival from commencing first-line chemotherapy was 39 weeks (95% CI, 34­45 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.

Advanced aggressive fibromatosis: Effective palliation with chemotherapy.

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/m(2) 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.

Clinical benefit of second-line palliative chemotherapy in advanced soft-tissue sarcoma.

Background. This paper aimed to assess the utility of second-line chemotherapy in patients with advanced soft-tissue sarcoma. Materials and Methods. A retrospective search of a prospectively maintained database identified patients treated between 1991 and 2005. Patients with gastrointestinal stromal tumours, small round cell tumours, and Ewing's sarcoma were excluded. Response was assessed using WHO and RECIST. Patients who achieved stable disease for 6 months or more were classified as having disease control. Results. Three hundred and seventy-nine patients received second-line chemotherapy. Eighty-six (22.7%) achieved disease control. Median duration of response was 11 months (95% CI: 9-13). On multivariate analysis, pathological subtype, absence of lung metastases, and the use of combination chemotherapy were independent predictors of disease control. Twenty-eight (16.1%) patients who failed to respond to first-line therapy achieved disease control. Eight (2.1%) patients had sufficient downstaging to enable complete surgical resection. Progression-free survival was 23% at 6 months. Median overall survival was 8 months (95% CI: 7-10 months). On multivariate analysis, synovial histology and absence of lung metastases were associated with improved survival. Conclusion. Second-line chemotherapy can provide clinical benefit in over 20% of soft-tissue sarcoma patients.

Pegylated liposomal doxorubicin, an effective, well-tolerated treatment for refractory aggressive fibromatosis.

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 50mg/m(2) over 1h 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.

Significant clinical benefit of first-line palliative chemotherapy in advanced soft-tissue sarcoma: retrospective analysis and identification of prognostic factors in 488 patients.

BACKGROUND: The efficacy of palliative chemotherapy was investigated in a large group of patients with advanced soft-tissue sarcomas (STS) treated on routine palliative protocols. METHODS: Patients with STS who had first-line chemotherapy for advanced and/or metastatic disease between 1991 and 2005 were identified from the Royal Marsden Hospital's sarcoma database. Patients with Ewing sarcoma, rhabdomyosarcoma, desmoplastic small round cell tumor, and gastrointestinal stromal tumors were excluded from the study. RESULTS: In all, 488 patients (242 male, 246 female) fulfilled the study criteria. The median age was 49 years and the majority (83%) received chemotherapy for metastatic disease. The most common histologic subtypes were leiomyosarcoma (35%) synovial sarcoma (13%), liposarcoma (10%), and malignant fibrous histiocytoma (10%). In all, 61% received single-agent chemotherapy, usually doxorubicin. An objective response was reported in 33% of patients (53% in those with synovial sarcoma); 22% had stable disease and 45% derived 'clinical benefit' (objective responses + stable disease for >or= 6 months). Median duration of response was 9 months and median posttreatment overall survival (OS) was 12 months. In multivariate analysis, age <40 years, liposarcoma, and synovial histology were found to be positive, and bone involvement to be negative, independent prognostic factors. Patients treated with combination chemotherapy experienced longer OS than those treated with a single agent. CONCLUSIONS: Palliative chemotherapy may be beneficial in approximately half of patients with advanced STS. Synovial sarcoma and liposarcoma subtypes have a better prognosis. However, the overall poor outcome of these patients indicates the need to continue the search for more effective agents.